"Looks do matter"-visual attentional biases in adolescent girls with eating disorders viewing body images - Horndasch, Stefanie; Kratz, Oliver; Holczinger, Anna; Heinrich, Hartmut; Hönig, Florian Thomas; Nöth, Elmar; Moll, Gunther (Psychiatry Research, 2012)
Visual attention allocation of adolescent girls with and without an eating disorder while viewing body images of underweight, normal-weight and overweight women was studied using eye tracking. While all girls attended more to specific body parts (e.g. hips, upper legs), eating-disordered girls showed an attentional bias towards unclothed body parts.
Keywords: Eating disorder; Attentional bias; Eye tracking

Low amounts of bisecting glycans characterize cerebrospinal fluid-borne IgG - Knopf, Jasmin; Magorivska, Iryna; Maier, Jan-Niklas; Spitzer, Philipp; Bilyy, Rostyslav; Biermann, Mona; Hychka, Kateryna; Bondt, Albert; Wuhrer, Manfred; Toes, Rene E. M.; Schett, Georg; Herrmann, Martin; et al. (Journal of Neuroimmunology, 2018)
Immunoglobulin G (IgG) harbors a conserved N-glycosylation site which is important for its effector functions. Changes in glycosylation of IgG occur in many autoimmune diseases but also in physiological conditions. Therefore, the glycosylation pattern of serum IgG is well characterized. However, limited data is available on the glycosylation pattern of IgG in cerebrospinal fluid (CSF) compared to serum. Here, we report significantly reduced levels of bisected glycans in CSF IgG. Galactosylation and sialylation of IgG4 also differed significantly. Therefore, we propose a common mechanism mediating glycosylation changes of IgG at the transition from serum to CSF in steady state conditions.
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Low digit ratio (2D:4D) and late pubertal onset indicate prenatal hyperandrogenziation in alcohol binge drinking - Lenz, Bernd; Bouna-Pyrrou, Polyxeni; Mühle, Christiane; Kornhuber, Johannes (Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2018)
BACKGROUND: Alcohol binge drinking behavior is an important public health issue. Causal rodent and human associational studies show that reinforcement of prenatal androgen signaling increases alcohol consumption in adulthood. However, the effects of prenatal androgen exposure on adult binge drinking patterns have not been investigated yet. METHOD: We analyzed data from 2225 participants of an online survey (conducted 06-07/2016) to evaluate biomarkers for prenatal androgen exposure (second-to-fourth finger length ratio [2D:4D], age at spermarche or menarche as hallmark for pubertal onset) in binge drinking (≥1 episode of 15+, 10+, and/or 5+ standard drinks of 13 g of alcohol within 2 h during the 24 month- and 2 week-recall periods). RESULTS: Men reported binge drinking more often than women (ORs > 1.4, P < .001). For the 24 month-recall period, binge drinkers showed lower 2D:4D (P = .006) and reported later pubertal onset (P = .022) than non-binge drinkers. These findings consistently suggest excess prenatal androgen exposure in adult binge drinkers. Moreover, 2D:4D was negatively associated with severity (15+/10+/5+/non-binge drinking, P = .005) and frequency of binge drinking episodes (P = .044). All of these effects were stronger in men than in women. For the 2 week-recall period, the biomarkers were not significantly related to binge drinking behavior. CONCLUSION: Our results indicate that increased prenatal androgen exposure is involved in the development of alcohol binge drinking behavior in adults.
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Low digit ratio (2D:4D) in male suicide victims - Lenz, Bernd; Thiem, Daniela; Bouna-Pyrrou, Polyxeni; Mühle, Christiane; Stoessel, Christina; Betz, Peter; Kornhuber, Johannes (Journal of Neural Transmission, 2016)
Although women attempt suicides equally or more often than men do, men are more likely to die of suicide than women (sex paradox of suicidal behavior). Furthermore, the male traits of aggression and impulsivity predict suicide completion. Here, we studied the second-to-fourth-finger length ratio (2D:4D), a proxy for prenatal androgen exposure, in 46 suicide corpses and 25 non-suicide corpses. We report significantly lower 2D:4D in male suicide corpses than non-suicide corpses (p = .030, partial ? (2) = .147). There was no significant association between 2D:4D and the suicide method. Our findings indicate increased risk of suicide following higher prenatal androgen exposure in males. The results may improve future efforts to predict and prevent suicides.
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Lower digit ratio (2D:4D) in alcohol dependence: Confirmation and exploratory analysis in a population-based study of young men - Lenz, Bernd; Mühle, Christiane; Kornhuber, Johannes (Addiction Biology, 2019)
Moderately sized, case-control studies have related alcohol dependence in middle-aged in-patients to lower second-to-fourth finger length ratio (2D:4D), a proxy for prenatal hyperandrogenization. As primary aim, we here intended to confirm that lower 2D:4D is also associated with Diagnostic and Statistical Manual of Mental Disorders (DSM)–IV/-5 alcohol dependence and alcohol use disorder in a large population-based cohort of young males. Exploratory aims included underlying mechanisms. We analyzed self-reported data on 2D:4D, DSM-IV/-5 criteria, anticipated subjective responses to alcohol, and willingness to purchase alcoholic drinks from 4989 Swiss men of the Cohort Study on Substance Use Risk Factors (C-SURF). The mean of right-hand 2D:4D and left-hand 2D:4D was lower in men with DSM-IV alcohol dependence than in those without (0.975 vs 0.981, P =.035) and lower in men with moderate to severe (0.974) than in those with mild (0.982, P =.001) or no (0.981, P =.003) DSM-5 alcohol use disorder. Moreover, mean 2D:4D was lower in those reporting recent use of health services due to substance use problems (0.968 vs 0.981, P =.046). Lower mean 2D:4D correlated with a stronger anticipation to feel high following alcohol consumption (total cohort: ρ = −0.033, P =.026) and with a willingness to purchase more higher-priced alcoholic drinks (DSM-IV alcohol dependence subgroup: ρmin = −0.162, P =.002). This is the first population-based study on young males to demonstrate lower 2D:4D in DSM-IV alcohol dependence, DSM-5 alcohol use disorder, and the related use of health care services. We also provide novel insight into cognitive-behavioral mechanisms. These results should help to establish more effective preventive and therapeutic strategies targeting 2D:4D and prenatal androgen exposure.
CRIS-Team Scopus Importer:2019-08-27
Keywords: 2D:4D; alcohol dependence; alcohol use disorder; digit ratio

Lower Digit Ratio (2D:4D) Indicative of Excess Prenatal Androgen Is Associated With Increased Sociability and Greater Social Capital - Buchholz, Verena N.; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd; Gmel, Gerhard; Mohler-Kuo, Meichun; Foster, Simon; Marmet, Simon; Studer, Joseph (Frontiers in Behavioral Neuroscience, 2019)
Positive social interactions are crucial for human well-being. Elevated prenatal exposure to testosterone as indicated by a low second-to-fourth finger length ratio (2D:4D) relates to more aggressive/hostile behavior in men of low 2D:4D, especially in challenging situations. How much people enjoy interacting with others is determined by the personality trait sociability. Given its role in approach and avoidance behavior, sociability might also be influenced by prenatal sex hormones, but studies are inconclusive so far. Here, we investigated the association between 2D:4D and the personality trait sociability complemented by personal social capital and personal social network size, in a population-based cohort of 4998 men. Lower 2D:4D correlated significantly with higher trait sociability, bigger personal social capital, and larger personal social network size. These effects were consistent across both hands separately and their mean value. Furthermore, both factors of sociability (1) liking party and company of friends and (2) isolation intolerance, correlated significantly with the prenatal testosterone marker. The exploratory analysis revealed no link between 2D:4D and responses to the personality trait aggression items or items of anti-social-personality disorder. Our data suggest that prenatal androgen exposure organizes the brain with lasting effects on social behavior.
CRIS-Team WoS Importer:2020-01-03

Lower Emotion Regulation Competencies Mediate the Association between Impulsivity and Craving during Alcohol Withdrawal Treatment - Reichl, Daniela; Enewoldsen, Niklas; Weisel, Kiona; Saur, Sebastian; Fuhrmann, Lukas; Lang, Catharina; Berking, Matthias; Zink, Mathias; Ahnert, Andreas; Falkai, Peter; Kraus, Thomas; Hillemacher, Thomas; et al. (Substance Use & Misuse, 2022)
There is evidence that craving mediates the relationship between Impulsive Personality Traits (IPTs) and relapse during the treatment of an Alcohol Use Disorder (AUD). To provide tailored interventions, a deeper understanding of the relation between IPTs and craving, namely mediating processes, is important. Based on previous literature, we proposed that lower emotion regulation competencies mediate the relation between attentional as well as non-planning IPTs and craving. To investigate these interrelations, we used data from the baseline assessment (n = 320) of the SmartAssistEntz project (pre-registered in the German Clinical Trials Register [DRKS00017700]). Inpatients with a primary AUD diagnosis were interviewed using standardized self-report measures (IPTs: BIS-15, emotion regulation competencies: ERSQ, craving: OCDS-G short version) during their withdrawal treatment. Indirect effects were calculated using the SPSS macro PROCESS v3.5. Attentional as well as non-planning, but not motor, IPTs were associated with craving. Emotion regulation competencies mediated the relationship between attentional as well as non-planning IPTs and craving. Given their mediating role in the present study, it is interesting to investigate if addressing emotion regulation competencies can mitigate the negative influences of attentional and non-planning IPTs. The direct effect of attentional IPTs implicates alternate mediating processes, which should also be investigated in future research.
CRIS-Team Scopus Importer:2022-03-04
Keywords: alcohol use disorder; attentional; AUD; impulse control; indirect; Motor; non-planning; withdrawal treatment

Low income and schizophrenia risk: A narrative review - Schneider, Miriam; Müller, Christian P.; Knies, Andrea K. (Behavioural Brain Research, 2022)
Despite decades of research, the precise etiology of schizophrenia is not fully understood. Ample evidence indicates that the disorder derives from a complex interplay of genetic and environmental factors during vulnerable stages of brain maturation. Among the plethora of risk factors investigated, stress, pre- and perinatal insults, and cannabis use have been repeatedly highlighted as crucial environmental risk factors for schizophrenia. Compelling findings from population-based longitudinal studies suggest low income as an additional risk factor for future schizophrenia diagnosis, but underlying mechanisms remain unclear. In this narrative review, we (1) summarize the literature in support of a relationship between low (parental) income and schizophrenia risk, and (2) explore the mediating role of chronic stress, pre- and perinatal factors, and cannabis use as established risk factors for schizophrenia. Our review describes how low income facilitates the occurrence and severity of these established risk factors and thus contributes to schizophrenia liability. The broadest influence of low income was identified for stress, as low income was found to be associated with exposure to a multitude of severe psychological and physiological stressors. This narrative review adds to the growing literature reporting a close relationship between income and mental health.
CRIS-Team Scopus Importer:2022-09-09
Keywords: Income; Mental illness; Risk factors; Schizophrenia; Stress

Low-threshold consulting services for dementia : Quality criteria from a provider's point of view - Ulbrecht, G.; Grässel, Elmar; Nickel, F.; Kolominsky-Rabas, Peter (Der Nervenarzt, 2018)
BACKGROUND: Low-threshold consulting services are becoming increasingly more important as an addition to outpatient and inpatient services. OBJECTIVE: What quality criteria do providers of low-threshold consulting services for family caregivers of people with dementia have? MATERIAL AND METHODS: Telephone interviews with 36 providers of family counseling, support groups, care course. Qualitative content analysis according to Mayring complemented by a literature search. RESULTS: The quality criteria of the providers are based on frequent, ongoing, daily life-oriented, family-oriented, relief-providing, professional, and cross-linked services. CONCLUSION: Increased cooperation and coordination of all involved stakeholders is necessary to improve the knowledge and utilization of the services and the qualitative orientation.
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Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study - Swoboda, Caroline; Deloch, Lena; von Zimmermann, Claudia; Richter-Schmidinger, Tanja; Lenz, Bernd; Kornhuber, Johannes; Mühle, Christiane (International Journal of Molecular Sciences, 2022)
Macrophage migration inhibitory factor (MIF) is a controversially discussed inflammatory marker in major depressive disorder (MDD). While some studies show an association of high MIF protein levels with depression, animal models have yielded conflicting results. Thus, it remains elusive as to whether MIF plays an anti- or pro-depressive role. Therefore, we aimed to examine the potential of MIF at the genetic, expression and protein levels as a risk factor and biomarker to diagnose, monitor, or predict the course of MDD. Patients with a current major depressive episode (n = 66 with, and n = 63 without, prior medication) and remitted patients (n = 39) were compared with healthy controls (n = 61). Currently depressed patients provided a second blood sample after three weeks of therapy. Depression severity was assessed by self-evaluation and clinician rating scales. We genotyped for three MIF polymorphisms and analyzed peripheral MIF expression and serum levels. The absence of minor allele homozygous individuals in the large group of 96 female patients compared with 10-16% in female controls suggests a protective effect for MDD, which was not observed in the male group. There were no significant group differences of protein and expression levels, however, both showed predictive potential for the course of depression severity in some subgroups. While MIF protein levels, but not MIF expression, decreased during treatment, they were not associated with changes in depression severity. This project is the first to investigate three biological levels of MIF in depression. The data hint toward a genetic effect in women, but do not provide robust evidence for the utility of MIF as a biomarker for the diagnosis or monitoring of MDD. The observed predictive potential requires further analysis, emphasizing future attention to confounding factors such as sex and premedication.
CRIS-Team WoS Importer:2023-01-20
Keywords: major depressive disorder; macrophage migration inhibitory factor (MIF); biomarker; inflammation

Making a case for constructive reductionism - Müller, Christian P. (Behavioral and Brain Sciences, 2019)
Borsboom and colleagues argue that reductionism in psychopathology research has not provided the expected insights. Instead, they suggest a systems approach of interacting syndromes, which, however, falls short of a perspective for empirical testing. Here, a combination of both approaches is suggested: a reductionistic empirical approach allowing testability, synergistic with a constructivistic systems appraisal of syndrome networks - a constructive reductionism.
CRIS-Team Scopus Importer:2019-05-02

Male depression syndrome is characterized by pronounced Cluster B personality traits - Sedlinská, Terezie; Mühle, Christiane; Richter-Schmidinger, Tanja; Weinland, Christian; Kornhuber, Johannes; Lenz, Bernd (Journal of Affective Disorders, 2021)
Background: Male depression syndrome (Male-DS) refers to alternative depression symptoms related to the male sex, such as externalizing behaviors, emotional suppression, substance misuse, and risk-seeking. Although these symptoms contribute to gender bias in the diagnosis of depression, Male-DS can be found in both sexes. In this cross-sectional study, we analyzed associations between Male-DS and clinical personality accentuations. Methods: We compared clinical personality accentuations between 78 depressed patients with high Male-DS scores (46% women; mean age ± standard error of the mean: 36.5 ± 1.6 years) and 76 depressed patients with low Male-DS scores (43% women; age 44.8 ± 1.7 years). We also explored differences between the two patient groups and 176 healthy controls (51% women; age 37.2 ± 1.0 years). Results: Depressed patients with high Male-DS scores showed stronger borderline (partial η2 0.121), impulsive (0.112), and antisocial (0.078) personality accentuations than those with low Male-DS scores after Bonferroni adjustment and controlling for sex, depression severity, and age. Relative to healthy controls, patients with high Male-DS values scored higher in all personality dimensions except for the narcissistic dimension. Patients with low Male-DS values scored higher in all Cluster A and C dimensions and the impulsive and borderline dimensions, but their scores were lower in the narcissistic dimension. Limitations: Cross-sectional design and focus on in-patients. Conclusions: We found pronounced Cluster B personality in patients with high Male-DS scores versus patients with low scores. Further prospective research is needed to verify that Cluster B personality traits represent a pre-morbid risk factor for Male-DS.
CRIS-Team Scopus Importer:2021-08-06
Keywords: Antisocial; Borderline; Impulsive; Male depression; Personality

Manchmal trink ich auch Wasser… – Alkoholkonsum von Menschen mit leichter kognitiver Beeinträchtigung - Donath, Carolin; Grässel, Elmar; Scheuermann, Julia-Sophia; Bösl, Sophia; Scheerbaum, Petra (Psychiatrische Praxis, 2023)
Aim Risky alcohol consumption increases the risk of dementia for people with mild cognitive impairment (MCI). The aim of this study is to assess alcohol consumption in people with MCI. Methods Socio-demographics, 12-month prevalence, 30-d prevalence, prevalence of risky consumption ( > 10 g/20 g/d pure alcohol for women/men) and binge drinking (≥ 50 g pure alcohol on one occasion) were recorded in 270 people (≥ 60 years) with MCI from the German RCT "Brainfit-Nutrition" in 2022. Results Approximately half of the people with MCI (50.8 %) drink at least once a week. About one fifth (17.0 %) of participants met the criterion for binge drinking; every third woman (34.8 %) and every fifth man (18.6 %) crossed the line to risky consumption in the last 30 d. Discussion Generally, people with MCI show similar consumption prevalence as the 65 + German general population. However, the prevalence of risky consumption in women with MCI is significantly higher.
CRIS-Team Scopus Importer:2023-09-22
Keywords: alcohol abstinence; alcohol drinking; binge drinking; cognitive dysfunction; sociodemographic factors

Manipulating motor performance and memory through real-time fMRI neurofeedback - Scharnowski, Frank; Veite, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jorn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus (Biological Psychology, 2015)
Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects.
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Manualised group therapy concept for patients with alcoholic cirrhosis awaiting liver transplantation. - Erim, Yesim; Möller, Elisabeth; Beckebaum, Susanne; Gerken, Guido; Broelsch, Christoph E.; Senf, Wolfgang (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2006)
Keywords: liver transplant; alcohol addiction; abstinence; psychoeducation; problem solving therapy

Manualized psychotherapy for the optimization of immunosuppressant adherence following kidney transplantation: Results of a feasibility study - Panyi, Noemi; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2017)
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Mapping bone marrow metastasis in neuroblastoma by deep multiplex imaging and transcriptomics - Lazic, Daria; Kromp, Florian; Rifatbegovic, Fikret; Repiscak, Peter; Mivalt, Filip; Halbritter, Florian; Bernkopf, Marie; Bileck, Andrea; Ussowicz, Marek; Ambros, Inge M.; Ambros, Peter F.; Gerner, Christopher; et al. (CANCER RESEARCH, 2022)
CRIS-Team WoS Importer:2023-04-07

Markers of Prenatal Androgen Exposure Correlate With Online Sexual Compulsivity and Erectile Function in Young Men - Buchholz, Verena N.; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Frontiers in Psychiatry, 2021)
Pornography addiction and sexual dysfunction are increasingly prevalent in young men. Previous studies suggest that prenatal androgen exposure plays a role in addiction and sexual functionality. Here, we tested whether lower second-to-fourth finger length ratio (2D:4D) and later age at spermarche, both putative indicators of higher androgen levels in utero, correlate with online sexual compulsivity (OSC scale of ISST), erectile function (IIEF-5), and ejaculatory control (PEPA) in 4,370 young men (age IQR: 25-26 years) of the Cohort Study on Substance Use Risk Factors. Statistical analyses revealed that lower 2D:4D correlated with higher scores on the OSC scale. Moreover, higher age at spermarche correlated with higher OSC scores and decreased erectile function. Interestingly, OSC severity, but not the frequency of pornography use, correlated negatively with erectile function and ejaculatory control. This is the first study to associate two independent proxies of prenatal testosterone level with OSC. These findings provide novel insight into intrauterine predisposition of sexual behavior and related sexual function in adulthood.
CRIS-Team WoS Importer:2021-05-07

Masculine depression and its problem behaviors: use alcohol and drugs, work hard, and avoid psychiatry! - von Zimmermann, Claudia; Hübner, Magdalena; Mühle, Christiane; Müller, Christian P.; Weinland, Christian; Kornhuber, Johannes; Lenz, Bernd (European archives of psychiatry and clinical neuroscience, 2023)
The gender role influences vulnerability to mental illness. Substance use, even critical in scale, is perceived as masculine, just like hard (over-)work, while not seeking help. With the ongoing separation between gender and sex, masculine norms become more relevant also to females’ mental health. The male depression concept highlights the role of male symptoms in affective disorders. However, the empirical evidence is still limited. Here, we use the denomination ‘masculine depression’ to open the category for female patients and tested substance use patterns, health services’ utilization, and working hours as predictors in a case–control study of 163 depressed in-patients (44% women; masculine vs. non-masculine depression according to a median split of the Male Depression Rating Scale-22) and 176 controls (51% women). We assessed higher depression severity in patients with masculine (vs. non-masculine) depression. Masculine depression (vs. non-masculine depression and vs. no depression) was predicted by more frequent and critical use of alcohol (including binge drinking), tobacco, and illicit drugs, and by longer working times. Moreover, fewer health services contacts due to mental complaints during the previous year were associated with masculine (vs. non-masculine) depression. Alarmingly, even critical substance misuse was not significantly associated with more frequent health services contacts; however, the higher the depression severity, the more contacts the patients reported. Here, we provide evidence that patients with masculine depression are highly burdened and undertreated, which applies equally to female and male patients. This study identified promising targets to establish specialized care offers.
CRIS-Team Scopus Importer:2023-03-10
Keywords: Alcoholism; Drug use; Help seeking; Male depression; Masculine depression; Nicotine; Substance use

Masking and mirror - What can we learn from facial recognition in patients with (partial) Dissociative Identity Disorder? - Schaeflein, Eva; Sattel, Heribert; Sack, Martin (Journal of Trauma & Dissociation, 2019)
CRIS-Team WoS Importer:2019-10-29

Maternal depression and child development: A prospective analysis of consequences, risk and protective factors - Roetner, Jakob; Petry, Janna; Niekamp, Julia; Maschkel, Janina; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; Moll, Gunther; Eichler, Anna (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2022)
Maternal depression and child development: A prospective analysis of consequences, risk and protective factors Abstract. Objective: Maternal stress, specifically maternal mental health problems, are considered risk factors for child development. The literature suggests that prenatal depressive symptoms as well as depressive symptoms are a widespread phenomenon during the further development of the child and have repeatedly been shown to have adverse effects on child mental health outcomes. The present study examined the longitudinal relationships between maternal depression (prenatal, postnatal, during childhood and adolescence) and child mental health from childhood to adolescence. Possible risk and protective factors were also considered. Method: N = 112 mothers were assessed for depressive symptoms via a questionnaire at four different timepoints (prenatal, T1; postnatal, T2; during childhood, T3; during adolescence, T4). Children's externalizing and internalizing symptoms (50.9 % girls) were assessed by their mothers both during childhood (M = 7.68, SD = 0.76 years) and during adolescence (M = 13.23, SD = 0.27 years). We evaluated the relationships between maternal depressive symptoms and children's externalizing/internalizing symptoms using multiple regression models and analyzed possible risk and protective factors using moderation analysis. Results: Externalizing/Internalizing symptoms were not directly associated with maternal depressive symptoms, while associations between such symptoms and maladaptive behavior were found in adolescents. The socioeconomic status of families showed a different risk profile for prenatal and postnatal depressive symptoms. The IQ of the children proved to be a risk factor for internalizing symptoms. Conclusions: Maternal depressive symptoms at any time during child development - in combination with further risk factors - have an impact on child mental health. The early identification of maternal symptoms followed by interventions to differentiate between prenatal and postnatal depression - especially in the context of socioeconomic status - are highly relevant for child development.
CRIS-Team WoS Importer:2022-04-08
Keywords: Pränatale Depressivität; kindliche Erlebens- und Verhaltensauffälligkeiten; Risiko- und Schutzfaktoren; sozioökonomischer Status; Intelligenzquotient; Prenatal depression; child behavior; risk and protective factors; socioeconomic status; intelligence quotient

Maternal perinatal or current depressive symptoms and parenting behavior in middle childhood - Zalan, Vera; Ziegler, Clara; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (International Attachment Conference, 2017)

Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type - Adami, Pamela V. Martino; Orellana, Adelina; Garcia, Pablo; Kleineidam, Luca; Alarcon-Martin, Emilio; Montrreal, Laura; Aguilera, Nuria; Espinosa, Ana; Abdelnour, Carla; Rosende-Roca, Maitee; Pablo Tartari, Juan; Vargas, Liliana; et al. (Brain, 2022)
Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer's type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer's type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-beta 42 (A beta(42)), phospho-tau 181 (P-tau(181)) and total tau (T-tau) for conversion to dementia of the Alzheimer's type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal A beta(42), but normal P-tau(181) and T-tau, and in mild cognitive impairment patients with abnormal A beta(42), P-tau(181) and T-tau. MMP-10 was correlated with age in subjects with normal A beta(42), P-tau(181) and T-tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer's type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation.
CRIS-Team WoS Importer:2022-06-17

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the tumors of central nervous system (CNS) - Lukaszewicz-Zajac, Marta; Mroczko, Barbara; Kornhuber, Johannes; Lewczuk, Piotr (Journal of Neural Transmission, 2014)
Malignant neoplasms of the central nervous system (CNS) account for about 1.3 % of all tumors and 2.2 % of all cancer-related deaths. CNS tumors consist of heterogeneous group of neoplasms, including different variants of primary brain tumors and metastatic neoplasms. Advanced imaging techniques improved the neuroradiological diagnostic accuracy, although these methods are not specific enough for differentiation of CNS tumors, thus new approaches of patients' diagnosis are critically needed. The best solution for the diagnosis of patients with CNS tumors could be easily available biomarkers, which could be useful for the management of CNS neoplasms. Biomarkers should facilitate the diagnosis, monitor of treatment response and assess the prognosis of patients' survival. Currently, except for rare germ cell tumors, there is a lack of knowledge on biochemical markers for CNS neoplasms. Therefore, in this paper we summarized and referred a number of comprehensive reviews concerning the role of matrix metalloproteinases (MMPs) and their tissue inhibitors in tumor progression, including CNS neoplasms as well as described the general biochemistry of MMPs and their tissue inhibitors. Moreover, we presented the wide variety of previous findings, where authors suggested the significance of selected MMPs and their tissue inhibitors as potential biomarkers of human tumors, including CNS tumors. However, future investigations are needed to be performed before some of these enzymes could finally be used as biomarkers of specific types of CNS neoplasms.
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Measurement of angles in time-of-flight data for the automatic supervision of training exercises - Soutschek, Stefan; Kornhuber, Johannes; Maier, Andreas; Bauer, Sebastian; Kugler, Patrick; Hornegger, Joachim; Bebenek, Michael; Steckmann, Sven; von Stengel, Simon; Kemmler, Wolfgang (2010 4th International Conference on Pervasive Computing Technologies for Healthcare, Pervasive Health 2010, 2010)
In this paper we present a novel automatic system to supervise and support rehabilitation and fitness exercises. Goal of the system is to enable autonomous training of rehabilitation patients to support their recovery from movement restrictions as well as the prevention of age-related diseases such as osteoporosis. The system uses time-of-flight technology in order to measure movement angles in real-time. This novel setup is compared to a standard tracking system using visual markers. The measurements of both systems correlate with r values between 0.99 and 0.97 depending on the task domain. The mean error of the angle measurements is between 13 and 17 degrees.

Measurement of Stress Relief during Scented Cosmetic Product Application Using a Mood Questionnaire, Stress Hormone Levels and Brain Activation - Springer, Arielle; Hoeckmeier, Laura; Schicker, Doris; Hettwer, Stefan; Freiherr, Jessica (Cosmetics, 2022)
Nowadays, consumers’ well-being plays a decisive role in the purchase of cosmetic products. Although factors influencing consumers’ well-being are very subjective, companies strive to develop their products in such a way that a positive effect is likely. Therefore, methods are required to objectively explore and scientifically prove the product’s performance on humans. In this placebo-controlled study, a method was developed to evaluate relaxation or stress relief associated with one olfactory ingredient of a cosmetic product (face cream). Our experimental protocol included product testing in 25 healthy females, while an emotion questionnaire, analysis of saliva samples regarding the concentration of the hormones cortisol and α-amylase and mobile EEG measurement for quantification of the alpha brain waves before and after stress induction were conducted. It was shown that with this experimental design, the sample with the ingredient produced significant stress relief, as evidenced by significantly less negative emotion, significantly lowered cortisol levels and showed a trend towards a significant increase in alpha activity compared to placebo application. Our data provide evidence that this method is suitable for analyzing the differences between the two samples. In the future, this method can be utilized in the current or a further optimized form to evaluate the psychophysiological effects of cosmetic products on humans.
CRIS-Team Scopus Importer:2022-11-04
Keywords: alpha waves; amylase; aroma; brain activity; cortisol; EEG; fragrance; neuroscience; positive mood; relaxation; scent; skin care; well-being

MEASUREMENTS OF ADHERENCE IN RENAL TRANSPLANT RECIPIENTS: WHAT IS THE BEST METHOD? - Lieb, Marietta; Erim, Yesim (2018)
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Measuring covid-19 related health literacy in healthcare professionals—psychometric evaluation of the hl-cov-hp instrument - Hiltrop, Kati; Hiebel, Nina; Geiser, Franziska; Kriegsmann-Rabe, Milena; Gambashidze, Nikoloz; Morawa, Eva; Erim, Yesim; Weidner, Kerstin; Albus, Christian; Ernstmann, Nicole (International Journal of Environmental Research and Public Health, 2021)
Background: Thus far, there is no instrument available measuring COVID-19 related health literacy of healthcare professionals. Therefore, the aim of this study was to develop an instrument assessing COVID-19 related health literacy in healthcare professionals (HL-COV-HP) and evaluate its psychometric properties. Methods: An exploratory factor analysis, a confirmatory factor analysis, and descriptive analyses were conducted using data from n = 965 healthcare professionals. Health literacy related to COVID-19 was measured with 12 items, which were adapted from the validated HLS-EU-Q16 instrument measuring general health literacy. Results: Exploratory factor analysis demonstrated that 12 items loaded on one component. After removing one item due to its high standardized residual covariance, the confirmatory factor analysis of a one-factor model with 11 items showed satisfactory model fit (χ2 = 199.340, df = 41, χ2 /df = 4.862, p < 0.001, RMSEA = 0.063, CFI = 0.963 and TLI = 0.951). The HL-COV-HP instrument showed good internal consistency (Cronbach’s alpha 0.87) and acceptable construct reliability. Conclusions: The HL-COV-HP is a reliable, valid, and feasible instrument to assess the COVID-19 related health literacy in healthcare professionals. It can be used in hospitals or other healt hcare settings to assess the motivation and ability of healthcare professionals to find, understand, evaluate, and use COVID-19 information.
CRIS-Team Scopus Importer:2021-11-19
Keywords: Confirmatory factor analysis; COVID-19; Exploratory factor analysis; Health literacy; Healthcare professionals; SARS-CoV2-pandemic

Mechanical stability of a novel screw design after repeated insertion: can the double-thread screw serve as a back up? - Wiendieck, Kurt; Mueller, Helge; Buchfelder, Michael; Sommer, Bjoern (Journal of Neurosurgical Sciences, 2018)
BACKGROUND: We investigated mechanical pull-out behavior and tightening torque of a novel dual-core pedicle "6T screw" (6T). The aim of this study was to test if these changes in screw geometry are increasing the strength of the pedicle screw fixation after repeated insertion. METHODS: Three different types of pedicle screws were inserted in rigid foam blocks. Tightening torque and pull-out strength were measured during two repetitive insertions of a standard 6.5×45-mm conical screw. The third insertion into the pilot hole was performed using either standard 6.5×45-mm or 7.2×45-mm conical screws or the novel 6.5×45-mm (6T) screw. Additionally, we performed a surface analysis to investigate the bone/screw interface. RESULTS: The maximal tightening torque at the third insertion of the novel 6T screw was 194% higher compared to the standard 6.5×45-mm conical screw and 135% higher compared to the standard 7.2×45-mm conical screw. The pull-out strength of the 6T screw showed no significant changes, and surface analysis revealed a compression of the screw-foam interface due to the different internal diameters. CONCLUSIONS: The modified geometrical design of the 6T screw seems to have no statistically significant effect on the pull-out strength, although it achieved a higher tightening torque. This might be due to the different pitch angle cutting a new thread into the material and also to the enlarged inner diameter.
EVALuna2:214802

Mechanisms of a near-orthogonal ultra-fast evolution of human behaviour as a source of culture development - Müller, Christian P. (Behavioural Brain Research, 2020)
Current human culture is characterized by an increasing rate of accumulating potential and actually performed behaviours. The growth of behavioural complexity as well as the ex-vivo accumulation of human behaviour, here identified as the non-genetically inherited (NGI) behaviourome, cannot be explained by genetic/epigenetic mechanisms of inheritance. As human beings derive their socio-cultural identity predominantly from their behaviourome, mechanisms of heritability should predominantly consider inheritance and accumulation of the NGI behaviourome. Here we propose key mechanisms of a near-orthogonal and ultra-fast evolution of the NGI human behaviourome that provide a foundation not only of unique human culture development, but also of its recent acceleration. Thereby, the evolution of the human NGI behaviourome underlies similar features as genetically based evolution. However, specific mechanisms of mutation and selection work largely independent (orthogonal) from genetic/epigenetic mechanisms. We suggest a mechanism of how adaptive changes (mutations) in the NGI behaviourome work target-directed and how selection works on an ultra-fast time scale. Selection results are mostly not fatal for the individual which allows for a much increased mutation rate. For crucial accumulation of the NGI behaviourome, ex-vivo storage and retrieval systems of virtually unlimited capacity are described. We discuss the great potential of the human NGI behaviourome in respect of speculative human super-reproduction and homosexual reproduction success, as well as a possible unique human way to avoid reproduction failure in childlessness. Altogether, this model of human behavioural reproduction and accumulation of behaviour may provide a base for better understanding and prediction of uniquely human cultural development.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Behavioural accumulation; Behaviourome; Cultural evolution; Ex-vivo storage; Near-orthogonal evolution; Non-genetic inheritance; Replication failure; Super-reproduction; Targeted mutation; Ultra-fast selection

Meconium indicators of maternal alcohol abuse during pregnancy and association with patient characteristics - Goecke, Tamme W.; Burger, Pascal; Fasching, Peter; Bakdash, Abdulsallam; Engel, Anne; Haeberle, Lothar; Voigt, Franziska; Faschingbauer, Florian; Raabe, Eva; Maass, Nicolai; Rothe, Michael; Beckmann, Matthias; et al. (BioMed Research International, 2014)
Identification of women with moderate alcohol abuse during pregnancy is difficult. We correlated self-reported alcohol consumption during pregnancy and patient characteristics with objective alcohol indicators measured in fetal meconium.A total of 557 women singleton births and available psychological tests, obstetric data and meconium samples were included in statistical analysis. Alcohol metabolites (fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG)), were determined from meconium and correlated with patient characteristics.We found that 21.2% of the 557 participants admitted low-to-moderate alcohol consumption during pregnancy. Of the parameters analyzed from meconium, only EtG showed an association with alcohol history (P < 0.01). This association was inverse in cases with EtG value above 120 ng/g. These values indicate women with most severe alcohol consumption, who obviously denied having consumed alcohol during pregnancy. No other associations between socioeconomic or psychological characteristics and the drinking status (via meconium alcohol metabolites) could be found.Women who drink higher doses of ethanol during pregnancy, according to metabolite measures in meconium, might be less likely to admit alcohol consumption. No profile of socioeconomic or psychological characteristics of those women positively tested via meconium could be established.
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Media Exposure and Posttraumatic Stress Disorder: Review and Implications for Psychotherapy - Paslakis, Georgios; Graap, Holmer; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2015)
EVALuna:29531

Medical education in psychosocial disciplines in times of the COVID-19 pandemic - first experiences - Koelkebeck, Katja; Baessler, Franziska; Bittner, Robert; Frodl, Thomas; Gradl-Dietsch, Gertraut; Janowitz, Deborah; Jordan, Katja-Daniela; Kluge, Ina; Matthes, Oliver; Pinilla, Severin; Robitzsch, Anita; Strauss, Maria; et al. (Fortschritte der Neurologie - Psychiatrie, 2021)
Zusammenfassung
CRIS-Team WoS Importer:2021-05-28

Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study. - Hoertel, Nicolas; Rezaei, Katayoun; Sánchez-Rico, Marina; Delgado-Álvarez, Alfonso; Kornhuber, Johannes; Gulbins, Erich; Olfson, Mark; Ouazana-Vedrines, Charles; Carpinteiro, Alexander; Cougoule, Céline; Becker, Katrin Anne; Alvarado, Jesús M.; et al. (Pharmaceuticals, 2023)
Prior evidence indicates the potential central role of the acid sphingomyelinase (ASM)/ceramide system in the infection of cells with SARS-CoV-2. We conducted a multicenter retrospective observational study including 72,105 adult patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 31 August 2022. We examined the association between the ongoing use of medications functionally inhibiting acid sphingomyelinase (FIASMA), which reduces the infection of cells with SARS-CoV-2 in vitro, upon hospital admission with 28-day all-cause mortality in a 1:1 ratio matched analytic sample based on clinical characteristics, disease severity and other medications (N = 9714). The univariate Cox regression model of the matched analytic sample showed that FIASMA medication use at admission was associated with significantly lower risks of 28-day mortality (HR = 0.80; 95% CI = 0.72-0.88; p < 0.001). In this multicenter observational study, the use of FIASMA medications was significantly and substantially associated with reduced 28-day mortality among adult patients hospitalized with COVID-19. These findings support the continuation of these medications during the treatment of SARS-CoV-2 infections. Randomized clinical trials (RCTs) are needed to confirm these results, starting with the molecules with the greatest effect size in the study, e.g., fluoxetine, escitalopram, and amlodipine.
EVALuna2:553545

Melanoma Segmentation and Classification Employing Imaging and Graph Encodings - Rivera Monroy, Luis; Eberhardt, Martin; Ostalecki, Christian; Baur, Andreas; Vera, Julio; Maier, Andreas (Proceedings - 2022 IEEE/ACM International Conference on Connected Health: Applications, Systems and Engineering Technologies, CHASE 2022, 2022)
Histopathology imaging is crucial for the diagnosis and the decision on treating associated tissue diseases. For this reason, Computer-assisted approaches have gained popularity and shown promise in tasks such as segmentation and classification. However, collecting a significant amount of data and high-quality annotations remains a challenge. This work describes a pipeline for toponomy profiling on the population of cells that combines melanoma multidimensional fluorescent imaging, a supervised segmentation of the region of interest, and graph unsupervised embedded representation.The Multi-Epitope-Ligand Cartography (MELC) provides a range of data shown to be optimal for solving supervised and unsuper-vised tasks. This imaging technique and the methodology, such as the one presented here, are promising for further improvement in the study of diagnostic techniques and therapies for skin diseases, such as melanoma.
CRIS-Team Scopus Importer:2023-03-07
Keywords: melanoma; microscopy; neural networks; segmentation

Melatonin Acts as an Antidepressant by Inhibition of the Acid Sphingomyelinase/Ceramide System - Hoehn, Richard; Monse, Marlene; Pohl, Ella; Wranik, Sina; Wilker, Barbara; Keitsch, Simone; Soddemann, Matthias; Kornhuber, Johannes; Kohnen, Marcus; Edwards, Michael J.; Grassme, Heike; Gulbins, Erich (Neurosignals, 2016)
Melatonin has been shown to have antidepressive effects. We tested whether melatonin inhibits the acid sphingomyelinase/ceramide system and mediates its antidepressive effects via inhibition of the acid sphingomyelinase and a reduction of ceramide in the hippocampus. Antidepressants such as amitriptyline and fluoxetine were previously shown to inhibit the acid sphingomyelinase/ceramide system, which mediates neurogenesis and behavioral changes induced by these drugs.The effect of melatonin on the activity of the acid sphingomyelinase prior to and after treatment with melatonin was determined in cultured neurons and in vivo in the hippocampus of mice by measuring the consumption of [14C] sphingomyelin. Ceramide was measured by DAG kinase assay and fluorescence microscopy of the hippocampus and of cultured neurons. Neurogenesis in the hippocampus was analyzed by in vivo labeling with bromodeoxyuridine. Behavior was assessed in standardized tests.Melatonin treatment inhibited acid sphingomyelinase in vitro in cultured pheochromocytoma cells and in vivo in the hippocampus, which resulted in a reduction of ceramide in vitro and in vivo. The inhibition of the acid sphingomyelinase/ceramide system translated into increased neurogenesis in glucocorticosterone-stressed mice after treatment with melatonin, an effect that is abrogated in acid sphingomyelinase-deficient mice. Likewise, melatonin improved the depressive behavior of stressed mice, a therapeutic effect that was again absent in acid sphingomyelinase-deficient animals.These data indicate that the antidepressive effects of melatonin as well as the induction of neurogenesis triggered by this drug are mediated by an inhibition of the acid sphingomyelinase/ceramide system. This is the first study to identify melatonin as an inhibitor of the acid sphingomyelinase.
EVALuna:34135

Memorandum 'Development of health services research in Bavaria from the perspective of the Bavarian state working group 'health services research (LAGeV)': Status quo - Potential - strategies - Hollederer, Alfons; Braun, Günther E.; Dahlhoff, Gerhard; Drexler, Hans; Engel, Jutta; Grässel, Elmar; Häusler, Elisabeth; Heide, Herwig; Heuschmann, Peter; Hörl, Gabriele; Imhof, Hermann; Kaplan, Max; et al. (Gesundheitswesen, 2015)
The aim of the memorandum on the development of health services research (HSR) in Bavaria is to operationalise the global objectives of the State Working Group Health Services Research (LAGeV) and to collectively define future topics, specific implementation steps, methods as well as ways of working for the future course of the LAGeV. The LAGeV is an expert committee that integrates and links the competencies of different actors from science, politics and health care regarding HSR and facilitates their cooperation. The memorandum is based on an explorative survey among the LAGeV members, which identified the status quo of health services research in Bavaria, potential for development, important constraints, promoting factors, specific recommendations as well as future topics for the further development of HSR in Bavaria. From the perspective of the LAGeV members, the 12 most important future topics are: 1) Interface and networking research, 2) Innovative health care concepts, 3) Health care for multimorbid patients, 4)Health care for chronically ill patients, 5) Evaluation of innovations, processes and technologies, 6) Patient orientation and user focus, 7) Social and regional inequalities in health care, 8) Health care for mentally ill patients, 9) Indicators of health care quality, 10) Regional needs planning, 11) Practical effectiveness of HSR and 12) Scientific use of routine data. Potential for development of HSR in Bavaria lies a) in the promotion of networking and sustainable structures, b) the establishment of an HSR information platform that bundles information and results in regard to current topics and aims to facilitate cooperation as well as c) in the initiation of measures and projects. The latter ought to pinpoint health care challenges and make recommendations regarding the improvement of health care and its quality. The cooperation and networking structures that were established with the LAGeV should be continuously expanded and be used to work on priority topics in order to achieve the global objectives of the LAGe
Keywords: Bavaria; health services research; health system; innovative health care concepts; interface and networking research; quality of health care

Memory concerns, memory performance and risk of dementia in patients with mild cognitive impairment - Wolfsgruber, Steffen; Wagner, Michael; Schmidtke, Klaus; Froelich, Lutz; Kurz, Alexander; Schulz, Stefanie; Hampel, Harald; Heuser, Isabella; Peters, Oliver; Reischies, Friedel M.; Jahn, Holger; Luckhaus, Christian; et al. (PLoS ONE, 2014)
Concerns about worsening memory ("memory concerns"; MC) and impairment in memory performance are both predictors of Alzheimer's dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33-4.89), lower memory performance (HR = 0.63, 95%CI: 0.56-0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18-3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.
EVALuna2:23629

Mental and Physical Quality of Life in Actual Living Liver Donors Versus Potential Living Liver Donors: A Prospective, Controlled, Multicenter Study - Schulz, Karl-Heinz; Kroencke, Sylvia; Beckmann, Mingo; Nadalin, Silvio; Paul, Andreas; Fischer, Lutz; Nashan, Bjoern; Senf, Wolfgang; Erim, Yesim (Liver Transplantation, 2009)

Mental Disorder and Partnership: the Influence and Potential Burden of Affective Disorders on the Quality of Partnerships - Wieser, Erika; Richter-Schmiedinger, Tanja; Glueckler, Christine; Schmidt, Anika; Volkert, Julia; Reif, Andreas; Kornhuber, Johannes; Biermann, Teresa (Psychiatrische Praxis, 2016)
The aim of the present study was to explore the connection between affective disorders and various aspects of the quality of relationships and their impact on partnerships.In a multi-centric study, we used questionnaires to compare three groups of couples: 23 patients suffering from major depression and their partners, 32 patients with a bipolar disorder and their partners, and 49 healthy couples serving as controls.Regardless of the type of affective disorders, stability of the relationship, felt happiness and other measures of quality of partnership were significantly impaired in couples with an affected partner. Partners of patients experience a higher emotional strain in every day life compared to healthy controls. There was a trend showing that bipolar disorder leads to a greater burden and a higher conflict potential than depression.The present study deals with stabile partnerships in daily life, including severely disabled patients needing in-patient treatment. Taking into account the health status of their partners, we discuss various aspects of happiness, conflict potentials as well as impact on the quality of relationships.
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Mental distress in primary care patients: German patients compared with patients of Turkish origin - Sariaslan, S.; Morawa, E.; Erim, Yesim (Der Nervenarzt, 2014)
EVALuna2:24011
Keywords: Immigration; Turkish; Depression; Somatoform disorders; Primary care

Mental distress of physicians in the outpatient care throughout the COVID-19 pandemic: emotional and supportive human relations matter – Cross-sectional results of the VOICE-study - Mogwitz, Sabine; Albus, Christian; Beschoner, Petra; Erim, Yesim; Geiser, Franziska; Jerg-Bretzke, Lucia; Morawa, Eva; Steudte-Schmiedgen, Susann; Wintermann, Gloria-Beatrice; Weidner, Kerstin (BMC Health Services Research, 2023)
Background: The aim of this cross-sectional study was to evaluate the course of self-reported mental distress and quality of life (QoL) of physicians, working in the outpatient care (POC). Outcomes were compared with a control group of physicians working in the inpatient care (PIC), throughout the Corona Virus Disease (COVID)-19 pandemic. The impact of risk and protective factors in terms of emotional and supportive human relations on mental distress and perceived QoL of POC were of primary interest. Methods: Within the largest prospective, multi-center survey on mental health of health care workers (HCW), conducted during the first (T1) and second (T2) wave of the COVID-19 pandemic in Europe, we investigated the course of current burden (CB), depression (Patient Health Questionnaire-2), anxiety (Generalized Anxiety Disorder-2) and QoL, cross-sectionally, in n = 848 POC (T1: n = 536, T2: n = 312). The primary outcomes were compared with an age- and gender-matchted control group of n = 458 PIC (T1: n = 262, T2: n = 196). COVID-19-, work-related, social risk and protective factors were examined. Results: At T1, POC showed no significant differences with respect to CB, depression, anxiety, and QoL, after Bonferroni correction. Whereas at T2, POC exhibited higher scores of CB (Cohen´s d/ Cd =.934, p <.001), depression (Cd = 1.648, p < 001), anxiety (Cd = 1.745, p <.001), work-family conflict (Cd = 4.170, p <.001) and lower QoL (Cd =.891, p =.002) compared with PIC. Nearly all assessed parameters of burden increased from T1 to T2 within the cohort of POC (e.g. depression: CD = 1.580, p <.001). Risk factors for mental distress of POC throughout the pandemic were: increased work-family conflict (CB: ß =.254, p <.001, 95% CI:.23,.28; PHQ-2: ß =.139, p =.011, 95% CI:.09,.19; GAD-2: ß =.207, p <.001, 95% CI:.16,.26), worrying about the patients´ security (CB: ß =.144, p =.007, 95% CI:.07,.22; PHQ-2: ß =.150, p =.006, 95% CI:.00,.30), fear of triage situations (GAD-2: ß =.132, p =.010, 95% CI: -.04,.31) and burden through restricted social contact in spare time (CB: ß =.146, p =.003, 95% CI:.07,.22; PHQ-2: ß =.187, p <.001, 95% CI:.03,.34; GAD-2: ß =.156, p =.003, 95% CI: -.01,.32). Protective factors for mental distress and QoL were the perceived protection by local authorities (CB: ß = -.302, p <.001, 95% CI: -.39, -.22; PHQ-2: ß = -.190, p <. 001, 95% CI: -.36, -.02; GAD-2: ß = -.211, p <.001, 95% CI: -.40, -.03; QoL: ß =.273, p <.001, 95% CI:.18,.36), trust in colleagues (PHQ-2: ß = -.181, p <.001, 95% CI: -.34, -.02; GAD-2: ß = -.199, p <.001, 95% CI: -.37, -.02; QoL: ß =.124, p =.017, 95% CI:.04,.21) and social support (PHQ-2: ß = -.180, p <.001, 95% CI: -.22, -.14; GAD-2: ß = -.127, p =.014, 95% CI: -.17, -.08; QoL: ß =.211, p <.001, 95% CI:.19,.23). Conclusions: During the pandemic, the protective role of emotional and supportive human relations on the mental distress and quality of life of POC should be taken into account more thoroughly, both in practice and future research.
CRIS-Team Scopus Importer:2023-05-26
Keywords: COVID-19; COVID-19-related; General practioner; Mental distress; Optimism; Outpatient/ inpatient care; Physicians; Social support; Work-related risks/ resources

Mental health assessment of altruistic non-directed kidney donors: An EAPM consensus statement. - Potts, Stephen; Vitinius, Frank; Erim, Yesim; Gazdag, Gabor; Gribble, Robert; Ismail, Sohal Y.; Massey, Emma K.; Maldonado, Jose; Mucsi, Istvan; Novak, Marta; Niazi, Shehzad Khan; Schneekloth, Terry D.; et al. (Journal of psychosomatic research, 2018)

Mental health of Polish immigrants compared to that of the Polish and German populations - Morawa, Eva; Senf, Wolfgang; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2013)
Keywords: Immigrants; Mental Disorders; Depression; Anxiety; Somatic Complaints

Mental Health Screening of Syrian Refugees in Germany: The Refugee Health Screener - Borho, Andrea; Morawa, Eva; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2022)
Objectives: This study investigated the psychometric properties of the time-efficient Refugee Health Screener (RHS-13 and RHS-15) for assessing mental disorders among Syrian refugees in Germany.
CRIS-Team WoS Importer:2022-11-04

Mental Health Services for Refugees - Braehler, Elmar; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2017)
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Meta-analytic evidence for a sex-diverging association between alcohol use and body mass index. - Siegmann, Eva-Maria; Mazza, Massimiliano; Weinland, Christian; Kiefer, Falk; Kornhuber, Johannes; Mühle, Christiane; Lenz, Bernd (Scientific Reports, 2022)
Alcohol use is an important health issue and has been suggested to contribute to the burden produced by obesity. Both alcohol use and obesity are subject to sex differences. The available studies on the relationship between alcohol use and body mass index (BMI) report inconsistent results with positive, negative, and null findings which requests a meta-analytic approach. Therefore, we conducted a meta-analysis of case-control, cohort, and cross-sectional studies. The systematic literature search and data extraction was performed by 3 independent raters. We conducted sex-separated meta-analyses and -regressions to investigate how alcohol consumption associates with BMI. Our systematic literature search resulted in 36 studies with 48 data sets (Nmen = 172,254; kmen = 30; Nwomen = 24,164; kwomen = 18; Nunknown sex = 672,344; kunknown sex = 24). Alcohol use was associated with higher BMI in men (g = 0.08 [0.07; 0.09]) and lower BMI in women (g = - 0.26 [- 0.29; - 0.22]). Moreover, we found the amount of daily alcohol intake in men (β = 0.001 [0.0008; 0.0014]) and ethnicity in women (g[Caucasians] = - 0.45 versus g[Asians] = - 0.05; z = 11.5, p < 0.0001) to moderate these effects. We here identified sex-diverging relationships between alcohol use and BMI, found daily alcohol intake and ethnicity to sex-specifically moderate these effects, and argue that sex-specific choice of beverage type and higher amount of daily alcohol use in men than in women account for these observations. Future research is needed to provide empirical evidence for the underlying mechanisms.
EVALuna2:523162

Methylphenidate Treatment in Children with ADHD: Do EEG-Resting State Independent Networks Allow to Predict Response? - Heinrich, Hartmut; Vollebregt, Madelon; Palmer, Donna; Arns, Martijn (NEUROPSYCHOBIOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-26

Microstructural abnormalities of the posterior thalamic radiation and the mediodorsal thalamic nuclei in females with anorexia nervosa - A voxel based diffusion tensor imaging (DTI) study - Frieling, Helge; Fischer, Julia; Wilhelm, Julia; Engelhorn, Tobias; Bleich, Stefan; Hillemacher, Thomas; Dörfler, Arnd; Kornhuber, Johannes; De Zwaan, Martina; Peschel, Thomas (Journal of Psychiatric Research, 2012)
Gray matter abnormalities have been found in anorexia nervosa (AN) in several brain regions. However, little is known about white matter abnormalities under the condition of AN. To comprehensively assess the microstructural integrity of white matter pathways in women with anorexia nervosa, we performed voxel-based Diffusion Tensor Imaging (DTI). 21 women with AN according to DSM-IV criteria (9 of them recovered) and 20 female age-matched healthy control subjects were enrolled in the study. The patients had a mean body mass index of 17.2 kg/m2 (controls: 19.6 kg/m2). High resolution T1 images (MP-RAGE) and DTI were performed on a 3 T Siemens-scanner. Images were pre-processed and analyzed using a modified protocol for DTI in SPM2. Fractional anisotropy (FA) maps were compared using t-tests (p < 0.05, corrected). Compared with controls, AN patients showed bilateral reductions of FA maps in the posterior thalamic radiation which includes the optic radiation, and the left mediodorsal thalamus. Our study is limited by the small sample size and its cross-sectional design. A longitudinal design with the same individuals assessed when acutely ill and recovered is warranted for future studies. For the first time, the findings of our DTI study identified disturbances of associational and commissural fibers in the bilateral occipitotemporal white matter. The results help narrowing the prevailing biological models of AN by suggesting that body image distortion is related to microstructural alterations of white matter tracts connecting the extrastriate visual cortex with other brain regions involved in body perception. © 2012 Elsevier Ltd.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Anorexia nervosa; Extrastriate body area; Voxel-based apparent diffusivity coefficient mapping; Voxel-based diffusion tensor imaging

Microsurgical treatment of cranial and spinal dural arteriovenous fistulas for acute occlusion: a single institution's experience - Winter, F.; Böhm, Lea; Shawarba, Julia; Callegari, K.; Buchfelder, Michael; Roessler, Karl (Neurological Research, 2022)
Objectives: To determine the success rate of primary microsurgical treatment of both cranial and spinal dural arteriovenous fistulas (cdAVFs and sdAVFs).
CRIS-Team WoS Importer:2022-08-26

Microvesicles from cerebrospinal fluid of patients with Alzheimer’s disease display reduced concentrations of tau and APP protein - Spitzer, Philipp; Mulzer, Linda-Marie; Oberstein, Timo; Munoz, Luis Enrique; Lewczuk, Piotr; Kornhuber, Johannes; Herrmann, Martin; Maler, Juan Manuel (Scientific Reports, 2019)
Microvesicles are small membranous particles generated during cellular activation or stress. The analysis of the content and the surface of microvesicles allow conclusions about the cells they are originating from and the underlying pathology. Therefore, CSF microvesicles have been suggested to be promising targets to monitor the (etio)pathology of neurodegenerative diseases. Microvesicles in the CSF of 15 patients with Alzheimer’s disease and 15 controls were analyzed by flow cytometry regarding the levels of CD3, CD4, CD45, CD64, BACE1, Aβ, APP and tau. The results were replicated in a second cohort comprising 14 patients with Alzheimer’s disease and 9 controls. The levels of tau and APP were reduced in microvesicles of Alzheimer’s disease patients. A significant change was neither observed in the number of microvesicles nor in the expression of the other antigens. Tau and APP in microvesicles separated patients with Alzheimer’s disease from controls with an AUC of 0.84 and 0.89 respectively. We conclude that tau and APP in CSF microvesicles are promising biomarkers which could directly provide information about the Alzheimer pathology on a cellular level.
CRIS-Team Scopus Importer:2019-05-21

Migration und psychische Gesundheit - Erim, Yesim; Morawa, Eva (Uexküll Psychosomatic Medicine. Theoretical models and clinical practice., 2016)

Mindfulness and skills-based eHealth intervention to reduce distress in cancer-affected patients in the Reduct trial: Intervention protocol of the make it training optimized - Heinen, Jana; Bäuerle, Alexander; Schug, Caterina; Krakowczyk, Julia Barbara; Strunk, Sven Erik; Wieser, Alexandra; Beckord, Jil; Jansen, Christoph; Dries, Sebastian; Pantförder, Michael; Erim, Yesim; Zipfel, Stephan; et al. (Frontiers in Psychiatry, 2022)
Introduction: Cancer-affected patients experience high distress due to various burdens. One way to expand psycho-oncological support is through digital interventions. This protocol describes the development and structure of a web-based psycho-oncological intervention, the Make It Training optimized. This intervention is currently evaluated in the Reduct trial, a multicenter randomized controlled trial. Methods: The Make It Training optimized was developed in six steps: A patient need and demand assessment, development and acceptability analysis of a prototype, the formation of a patient advisory council, the revision of the training, implementation into a web app, and the development of a motivation and evaluation plan. Results: Through a process of establishing cancer-affected patients’ needs, prototype testing, and patient involvement, the Make It Training optimized was developed by a multidisciplinary team and implemented in a web app. It consists of 16 interactive self-guided modules which can be completed within 16 weeks. Discussion: Intervention protocols can increase transparency and increase the likelihood of developing effective web-based interventions. This protocol describes the process and results of developing a patient-oriented intervention. Future research should focus on the further personalization of web-based psycho-oncological interventions and the potential benefits of combining multiple psychotherapeutic approaches.
CRIS-Team Scopus Importer:2022-11-25
Keywords: cancer; e-mental health; intervention protocol; MBSR; psycho-oncology; skills training; web-based intervention

Mindfulness-Based Approaches to Addiction Prevention and Treatment for Children and Adolescents: Thematic Background and Overview of the Ongoing IMAC-Mind Network Achtsamkeitsorientierte Ansätze der Suchtprävention und -therapie bei Kindern und Jugendlichen Thematischer Hintergrund und Überblick zu dem laufenden IMAC-Mind Verbund - Arnaud, Nicolas; Banaschewski, Tobias; Nees, Frauke; Buchholz, Verena Nadine; Klein, Michael; Reis, Olaf; Legenbauer, Tanja; Zapf, Antonia; Thomasius, Rainer (Sucht, 2022)
Background: Adolescence is considered a vulnerable phase for the development of addictive disorders, with a large proportion of young people who is affected. Central for addictive behavior are problems in the executive control and self-regulation of feelings, thoughts and behavior. For years the concept of mindfulness has been in public focus. Numerous neurobiological and clinical studies demonstrate the benefi ts of mindfulness-based interventions for strengthening executive regulation of stress and behavioral impulses in addictive disorders and comorbid psychological symptoms. Methods: Selective literature review on mindfulness and substance-related disorders in children and adolescents. Results: Empirical evidence to assess the utility of mindfulness programs to prevent and treat addictive disorders in children and adolescents is lacking to date. As part of the ongoing research network "IMAC-Mind: Improving Mental Health and Reducing Addiction Risk in Childhood and Adolescence through Mindfulness: Mechanisms, Prevention, and Treatment," the multivariate risk profi les for addictive disorders are being investigated and translated into mindfulness-based intervention models. Conclusion: This article derives research needs on addictive disorders and mindfulness from a youth-specifi c perspective and provides information about ongoing projects in the research network.
CRIS-Team Scopus Importer:2022-03-04
Keywords: children and adolescents; mindfulness; prevention; self-regulation; substance use disorder; therapy

Mindfulness-based Stress Reduction in Pregnancy: an App-Based Programme to Improve the Health of Mothers and Children (MINDFUL/PMI Study) - Lenz, Bernd; Eichler, Anna; Schwenke, Eva; Buchholz, Verena N.; Hartwig, Charlotte; Moll, Gunther; Reich, Karin; Mühle, Christiane; Volz, Bernhard; Titzmann, Adriana; Beckmann, Matthias; Heinrich, Hartmut; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Unfavourable intrauterine environmental factors increase the risk of delivery complications as well as postpartum developmental and behavioural problems in children and adolescents with ongoing effects into older age. Biomarker studies show that maternal stress and the use of alcohol and tobacco during pregnancy are associated with a higher intrauterine testosterone exposure of the child. The antenatal testosterone load, in turn, is a risk factor for lasting adverse health effects which extend into adulthood. A 15-week, mindfulness-oriented, app-based programme for the reduction of stress as well as for the reduction of alcohol and tobacco use in pregnant women is established. In the monocentre, prospective, controlled, and investigator-blinded MINDFUL/PMI (Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention) study, pregnant women carry out the programme. Its effect on antenatal testosterone exposure of the child is examined by assessing the index/ring finger length ratio and other biomarkers in the 1-year-old children. In addition, the programme's effects on self-regulation, the developmental status and the mental health of the children at the age of one year will be investigated. Additional aspects of the course of the pregnancy and delivery represent exploratory study objectives. This longitudinal study project is intended to improve the understanding of the impact of intrauterine environmental factors on early childhood development and health. Maternal stress as well as alcohol and tobacco use during pregnancy are modifiable factors and represent potential preventive targets.
EVALuna2:36366

miR-148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2 - Porstner, Martina; Winkelmann, Rebecca; Daum, Patrick; Schmid, Julia; Pracht, Katharina; Corte-Real, Joana; Schreiber, Sandra; Haftmann, Claudia; Brandl, Andreas; Mashreghi, Mir-Farzin; Gelse, Kolja; Hauke, Manuela; et al. (European Journal of Immunology, 2015)
B cells undergo affinity maturation and class switch recombination of their immunoglobulin receptors during a germinal center (GC) reaction, before they differentiate into long-lived antibody-secreting plasma cells (PCs). Transcription factors such as Bach2 and Mitf are essential during this process, as they delay premature differentiation of GC B cells by repressing Blimp-1 and IRF4, two transcription factors required for terminal PC differentiation. Therefore, Bach2 and Mitf expression must be attenuated in activated B cells to allow terminal PC differentiation, but the precise mechanism remains enigmatic. Here, we provide evidence that miR-148a, a small noncoding microRNA, fosters PC differentiation and survival. Next-generation sequencing revealed that miR-148a is the most abundant microRNA in primary human and murine PCs, and its expression is upregulated in activated murine B cells and coincides with Blimp-1 synthesis. miR-148a targets Bach2, Mitf and proapoptotic factors such as PTEN and Bim. When prematurely expressed, miR-148a promotes the differentiation and survival of plasmablasts and reduces frequencies of IgG1(+) cells in primary B-cell cultures. In summary, we propose that miR-148a is a new player in the regulatory network controlling terminal PC differentiation and could, therefore, be a therapeutic target for interfering with PC differentiation and survival.
EVALuna2:13632

Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases - Yambire, King Faisal; Fernandez-Mosquera, Lorena; Steinfeld, Robert; Mühle, Christiane; Ikonen, Elina; Milosevic, Ira; Raimundo, Nuno (eLife, 2019)
Perturbations in mitochondrial function and homeostasis are pervasive in lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses mitochondrial biogenesis and function in lysosomal storage diseases Niemann-Pick type C (NPC) and acid sphingomyelinase deficiency (ASM), in patient cells and mouse tissues. This mechanism is mediated by the transcription factors KLF2 and ETV1, which are both induced in NPC and ASM patient cells. Mitochondrial biogenesis and function defects in these cells are rescued by the silencing of KLF2 or ETV1. Increased ETV1 expression is regulated by KLF2, while the increase of KLF2 protein levels in NPC and ASM stems from impaired signaling downstream sphingosine-1-phosphate receptor 1 (S1PR1), which normally represses KLF2. In patient cells, S1PR1 is barely detectable at the plasma membrane and thus unable to repress KLF2. This manuscript provides a mechanistic pathway for the prevalent mitochondrial defects in lysosomal storage diseases.
CRIS-Team WoS Importer:2019-03-06

Mitragynine Attenuates Morphine Withdrawal Effects in Rats—A Comparison With Methadone and Buprenorphine - Hassan, Rahimah; Pike See, Cheah; Sreenivasan, Sasidharan; Mansor, Sharif M.; Müller, Christian P.; Hassan, Zurina (Frontiers in Psychiatry, 2020)
Background: Opiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenorphine have been implemented as substitution drugs. Despite MAT effectiveness, there are still limitations and side effects of using methadone and buprenorphine. Thus, other alternative therapies with less side effects, overdosing, and co-morbidities are desired. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts. Methods: Based on the morphine withdrawal model, rats were morphine treated with increasing doses from 10 to 50 mg/kg twice daily over a period of 6 days. The treatment was discontinued on day 7 in order to induce a spontaneous morphine abstinence. The withdrawal signs were measured daily after 24 h of the last morphine administration over a period of 28 abstinence days. In rats that developed withdrawal signs, a drug replacement treatment was given using mitragynine, methadone, or buprenorphine and the global withdrawal score was evaluated. Results: The morphine withdrawal model induced profound withdrawal signs for 16 days. Mitragynine (5–30 mg/kg; i.p.) was able to attenuate acute withdrawal signs in morphine dependent rats. On the other hand, smaller doses of methadone (0.5–2 mg/kg; i.p.) and buprenorphine (0.4–1.6 mg/kg; i.p.) were necessary to mitigate these effects. Conclusions: These data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment.
CRIS-Team Scopus Importer:2020-06-02
Keywords: buprenorphineI; kratom; methadone; mitragynine; morphine; substitution; withdrawal

Mitragynine (Kratom) impairs spatial learning and hippocampal synaptic transmission in rats - Hassan, Zurina; Suhaimi, Farah W.; Ramanathan, Surash; Ling, King Hwa; Effendy, Mohamad A.; Müller, Christian P.; Dringenberg, Hans C. (Journal of Psychopharmacology, 2019)
Background: Mitragynine is the major alkaloid of Mitragyna speciosa (Korth.) or Kratom, a psychoactive plant widely abused in Southeast Asia. While addictive effects of the substance are emerging, adverse cognitive effects of this drug and neuropharmacological actions are insufficiently understood. Aims: In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus. Methods: Male Sprague Dawley rats received daily (for 12 days) training sessions in the Morris water maze, with each session followed by treatment either with mitragynine (1, 5, or 10 mg/kg; intraperitoneally), morphine (5 mg/kg; intraperitoneally) or a vehicle. In the second experiment, we recorded field excitatory postsynaptic potentials in the hippocampal CA1 area in anesthetized rats and assessed the effects of mitragynine on baseline synaptic transmission, paired-pulse facilitation, and long-term potentiation. Gene expression of major memory- and addiction-related genes was investigated and the effects of mitragynine on Ca2+ influx was also examined in cultured primary neurons from E16–E18 rats. Results/outcomes: Escape latency results indicate that animals treated with mitragynine displayed a slower rate of acquisition as compared to their control counterparts. Further, mitragynine treatment significantly reduced the amplitude of baseline (i.e. non-potentiated) field excitatory postsynaptic potentials and resulted in a minor suppression of long-term potentiation in CA1. Bdnf and αCaMKII mRNA expressions in the brain were not affected and Ca2+ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine. Conclusions/interpretation: These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca2+ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.
CRIS-Team Scopus Importer:2019-06-18
Keywords: field excitatory postsynaptic potentials; Kratom; long-term potentiation; Mitragynine; Morris water maze

Mitragynine (Kratom)-Induced Cognitive Impairments in Mice Resemble delta 9-THC and Morphine Effects: Reversal by Cannabinoid CB1 Receptor Antagonism - Iman, Ismail Nurul; Ahmad, Nur Aimi Zawami; Yusof, Nurul Aiman Mohd; Talib, Ummi Nasrah; Norazit, Anwar; Kumar, Jaya; Mehat, Muhammad Zulfadli; Hassan, Zurina; Müller, Christian P.; Muzaimi, Mustapha (Frontiers in Pharmacology, 2021)
Kratom is a widely abused plant-based drug preparation with a global interest in recent years, well beyond its native grounds in Southeast Asia. Mitragynine, its major psychoactive constituent is known to exhibit opioid-like behavioral effects with resultant neuroplasticity in the brain reward system. Its chronic administration is associated with cognitive impairments in animal studies. However, the underlying molecular mechanism for such a deficit remains elusive. In this study, the involvement of cannabinoid type-1 (CB1) receptors in cognitive deficits after chronic mitragynine exposures was investigated for 28 days (with incremental dose sensitization from 1 to 25 mg/kg) in adult male Swiss albino mice using the IntelliCage(R) system. Chronic high-dose mitragynine exposure (5-25 mg/kg, intraperitoneal [i.p.]), but not low-dose exposure (1-4 mg/kg, i.p.), induced hyperlocomotion, potentiated the preference for sucrose reward, increased resistance to punishment, and impaired place learning and its reversal. Comparable deficits were also observed after chronic treatments with ?-9-tetrahydrocannabinol (THC, 2 mg/kg, i.p.) or morphine (5 mg/kg, subcutaneous). Mitragynine-, morphine-, and THC-induced learning and memory deficits were reversed by co-treatment with the CB1 receptor antagonist, NIDA-41020 (10 mg/kg, i.p.). A significant upregulation of CB1 receptor expression was found in the hippocampal CA1 region and ventral tegmental area after chronic high-dose mitragynine and morphine, whereas a downregulation was observed after chronic THC. In conclusion, the present study suggests a plausible role of the CB1 receptor in mediating the dose-dependent cognitive deficits after chronic high-dose mitragynine exposure. This also highlights the potential of CB1 receptor antagonism in ameliorating the cognitive deficits associated with long-term kratom/mitragynine consumption in humans.
CRIS-Team WoS Importer:2021-10-08

Mobile Technology Affinity in Renal Transplant Recipients - Reber, Sandra Therese; Scheel, J.; Stößel, Lisa; Schieber, Katharina; Jank, S.; Luker, C.; Vitinius, F.; Grundmann, F.; Eckardt, Kai-Uwe; Prokosch, Hans-Ulrich; Erim, Yesim (Transplantation Proceedings, 2018)
Medication nonadherence is a common problem in renal transplant recipients (RTRs). Mobile health approaches to improve medication adherence are a current trend, and several medication adherence apps are available. However, it is unknown whether RTRs use these technologies and to what extent. In the present study, the mobile technology affinity of RTRs was analyzed. We hypothesized significant age differences in mobile technology affinity and that mobile technology affinity is associated with better cognitive functioning as well as higher educational level.A total of 109 RTRs (63% male) participated in the cross-sectional study, with an overall mean age of 51.8 ± 14.2 years. The study included the Technology Experience Questionnaire (TEQ) for the assessment of mobile technology affinity, a cognitive test battery, and sociodemographic data.Overall, 57.4% of the patients used a smartphone or tablet and almost 45% used apps. The TEQ sum score was 20.9 in a possible range from 6 (no affinity to technology) to 30 (very high affinity). Younger patients had significantly higher scores in mobile technology affinity. The only significant gender difference was found in having fun with using electronic devices: Men enjoyed technology more than women did. Mobile technology affinity was positively associated with cognitive functioning and educational level.Young adult patients might profit most from mobile health approaches. Furthermore, high educational level and normal cognitive functioning promote mobile technology affinity. This should be kept in mind when designing mobile technology health (mHealth) interventions for RTRs. For beneficial mHealth interventions, further research on potential barriers and desired technologic features is necessary to adapt apps to patients' needs.
EVALuna:35443

Modulation of the hyaluronan-based extracellular matrix in mouse models of epilepsy - Blondiaux, A.; Jia, S.; Frischknecht, R.; Fejtová, Anna; Dityatev, A.; Gundelfinger, E.; Seidenbecher, C. (JOURNAL OF NEUROCHEMISTRY, 2019)
CRIS-Team WoS Importer:2019-08-16

Molecular and epigenetic consequences of pre- and postnatal trauma in a mouse model - Frey, Silke; Steigleder, R.; Distler, Jörg; Kratz, Oliver; Moll, Gunther; Golub, Yulia (2017)
EVALuna2:35017

Molecular targets of endothelial phosphatidic acid regulating major depressive disorder - Edwards, Michael J.; Wilson, Gregory C.; Keitsch, Simone; Soddemann, Matthias; Wilker, Barbara; Müller, Christian P.; Kornhuber, Johannes; Gulbins, Erich (Journal of Neurochemistry, 2022)
Major depressive disorder (MDD) is a severe disease of unknown pathogenesis with a lifetime prevalence of 10%. Therapy requires prolonged treatment that often fails. We have previously demonstrated that ceramide levels in the blood plasma of patients and in mice with experimental MDD are increased. Neutralization of blood plasma ceramide prevented experimental MDD in mice. Mechanistically, we demonstrated that blood plasma ceramide accumulated in endothelial cells of the hippocampus, inhibited phospholipase D (PLD) and thereby decreased phosphatidic acid in the hippocampus. Here, we demonstrate that phosphatidic acid binds to and controls the activity of phosphotyrosine phosphatase (PTP1B) in the hippocampus and thus determines tyrosine phosphorylation of a variety of cellular proteins including TrkB. Injection of PLD, phosphatidic acid, or inhibition of PTP1B abrogated MDD and normalized cellular tyrosine phosphorylation, including phosphorylation of TrkB and neurogenesis in the hippocampus. Most importantly, these treatments also rapidly normalized behavior of mice with experimental MDD. Since phosphatidic acid binds to and inhibits PTP1B, the lack of phosphatidic acid results in increased activity of PTP1B and thereby in reduced tyrosine phosphorylation of TrkB and other cellular proteins. Thus, our data indicate a novel pathogenetic mechanism of and a rapidly acting targeted treatment for MDD. (Figure presented.).
CRIS-Team Scopus Importer:2022-11-04
Keywords: behavior; major depression; phosphatidic acid; PTP1B; TrkB; tyrosine phosphorylation

Monitoring of direct oral anticoagulants plasma levels for secondary stroke prevention - Siedler, Gabriela; Macha, Kosmas; Stoll, Svenja; Plechschmidt, Johannes; Wang, Ruihao; Gerner, Stefan; Strasser, Erwin; Schwab, Stefan; Kallmünzer, Bernd (Journal of Thrombosis and Haemostasis, 2022)
Background: Patients with atrial fibrillation have a relevant risk for ischemic stroke despite the recommended use of direct oral anticoagulants (DOAC). The risk correlates with the functional DOAC plasma levels in clinical trials, but the value of their measurement in community use remains undetermined. Objectives: We aim to investigate the clinical implications and the prognostic value of DOAC plasma level measurement during steady state. Methods: In this observational clinical cohort study among patients with ischemic stroke and atrial fibrillation, 397 individuals on oral anticoagulants for secondary stroke prevention were included between 2016 and 2020. The functional DOAC plasma levels were measured during steady state. Early stroke recurrence within 3 months was recorded as the main outcome parameter. Results: Three hundred ninety-seven patients (201 female, mean age 78 [±9] years, median CHA2DS2VASc-Score 6 [interquartile range 5–7]) were included. Mean DOAC plasma trough level was 95.9 (±66.9) ng/ml. A high glomerular filtration rate (GFR) was an independent predictor of lower levels in a multivariate model (R coefficient: −0.174, P =.014). During follow-up, 10 patients (3%) suffered from early ischemic stroke recurrence despite the use of DOAC, while 10 clinically relevant bleeding complications occurred (3%). Ischemic stroke recurrence was associated with numerical lower plasma levels for patients on apixaban and dabigatran after propensity score matching. Conclusions: Monitoring of DOAC plasma levels could help to identify patients with increased risk for stroke recurrence and should be considered for certain subgroups, including patients with high GFR.
CRIS-Team Scopus Importer:2022-03-18
Keywords: atrial fibrillation; cardioembolic stroke; direct oral anticoagulants; ischemic stroke; secondary prevention

Moral Distress in Hospitals During the First Wave of the COVID-19 Pandemic: A Web-Based Survey Among 3,293 Healthcare Workers Within the German Network University Medicine - Schneider, Juliane Nora; Hiebel, Nina; Kriegsmann-Rabe, Milena; Schmuck, Jonas; Erim, Yesim; Morawa, Eva; Jerg-Bretzke, Lucia; Beschoner, Petra; Albus, Christian; Hannemann, Julian; Weidner, Kerstin; Steudte-Schmiedgen, Susann; et al. (Frontiers in Psychology, 2021)
Objective: The present study aimed to investigate the correlation between moral distress and mental health symptoms, socio-demographic, occupational, and COVID-19-related variables, and to determine differences in healthcare workers’ (HCW) moral distress during the first wave of the COVID-19 pandemic. Method: Data from 3,293 HCW from a web-based survey conducted between the 20th of April and the 5th of July 2020 were analyzed. We focused on moral distress (Moral Distress Thermometer, MDT), depressive symptoms (Patient Health Questionnaire-2, PHQ-2), anxiety symptoms (Generalized Anxiety Disorder-2, GAD-2), and increased general distress of nurses, physicians, medical-technical assistants (MTA), psychologists/psychotherapists, and pastoral counselors working in German hospitals. Results: The strongest correlations for moral distress were found with depressive symptoms, anxiety symptoms, occupancy rate at current work section, and contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nurses and MTA experienced significantly higher moral distress than physicians, psychologists/psychotherapists, and pastoral counselors. The average level of moral distress reported by nurses from all work areas was similar to levels which before the pandemic were only experienced by nurses in intensive or critical care units. Conclusion: Results indicate that moral distress is a relevant phenomenon among HCW in hospitals during the COVID-19 pandemic, regardless of whether they work at the frontline or not and requires urgent attention.
CRIS-Team Scopus Importer:2021-12-17
Keywords: anxiety; COVID-19; depression; healthcare; healthcare workers; mental health; moral distress

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis - Parma, Valentina; Ohla, Kathrin; Veldhuizen, Maria G.; Niv, Masha Y.; Kelly, Christine E.; Bakke, Alyssa J.; Cooper, Keiland W.; Bouysset, Cédric; Pirastu, Nicola; Dibattista, Michele; Kaur, Rishemjit; Liuzza, Marco Tullio; et al. (Chemical Senses, 2020)
Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
CRIS-Team Scopus Importer:2020-10-30
Keywords: head and neck surgery; olfaction; somatosensation

Mother-tongue psychotherapy by bilingual psychotherapists: Importance of language - Erim, Yesim (Migration und Transkulturalität, 2018)

Motives for using Kratom (Mitragyna speciosa Korth.) among regular users in Malaysia - Singh, Darshan; Narayanan, Suresh; Müller, Christian P.; Swogger, Marc T.; Chear, Nelson Jeng Yeou; Bin Dzulkapli, Eshal; Yusoff, Nur Sabrina Mohd; Ramachandram, Dinesh Sangarran; Leon, Francisco; Mccurdy, Christopher R.; Vicknasingam, Balasingam (Journal of Ethnopharmacology, 2019)
Ethnopharmacological relevance: The leaves of Mitragyna speciosa (Korth.) or kratom have been traditionally used in Malaysia and Thailand mainly to enhance work productivity, as a folk remedy for treating common ailments, and as a mood enhancer.
CRIS-Team WoS Importer:2019-03-06

Motor cortical inhibition in ADHD: modulation of the transcranial magnetic stimulation-evoked N100 in a response control task - D'Agati, Elisa; Hoegl, Thomas; Dippel, Gabriel; Curatolo, Paolo; Bender, Stephan; Kratz, Oliver; Moll, Gunther; Heinrich, Hartmut (Journal of Neural Transmission, 2014)
The N100 component, evoked by transcranial magnetic stimulation (TMS) and electroencephalography is associated with the activation of inhibitory cortical circuits and has recently been suggested as a potential marker of inhibition in attention-deficit/hyperactivity disorder (ADHD). The aim of the present ADHD study was to investigate the modulation of the TMS-N100 in go and nogo trials of a response control task considering stages of response preparation, activation, execution and inhibition. Eighteen children with ADHD and 19 typically developing children, aged 10-14 years, were assessed. TMS was delivered over the left motor cortex, the TMS-N100 was measured at electrode P3. The TMS-N100 was determined at rest and at different time points (50 ms before S2; 150, 300 and 500 ms after S2) in a cued go/nogo task (S1-S2 paradigm). Correlations between the TMS-N100 measures, MEP-related TMS measures (e.g., short-interval intracortical inhibition) and performance measures were calculated. At rest, the amplitude of TMS-N100 was not found to be significantly reduced in the ADHD group. During the go/nogo task, children with ADHD showed a smaller increase of TMS-N100 amplitude in go trials and a smaller decrease after inhibiting a response. In go trials, a lower TMS-N100 was associated with a smaller variability of reaction times. A smaller TMS-N100 modulation extends the picture of cortical inhibition deficits in ADHD. Findings suggest a functional involvement of the mechanisms underlying the TMS-N100 at the motor output stage.
EVALuna2:23882

Motor speech disorders in the nonfluent, semantic and logopenic variants of primary progressive aphasia - Staiger, Anja; Schroeter, Matthias L.; Ziegler, Wolfram; Schölderle, Theresa; Anderl-Straub, Sarah; Danek, Adrian; Duning, Thomas; Fassbender, Klaus; Fliessbach, Klaus; Jahn, Holger; Kasper, Elisabeth; Kornhuber, Johannes; et al. (Cortex, 2021)
Objective: Motor speech disorders (MSDs) are characteristic for nonfluent primary progressive aphasia (nfvPPA). In primary progressive aphasia (PPA) of the semantic (svPPA) and of the logopenic type (lvPPA), speech motor function is considered typically intact. However, knowledge on the prevalence of MSDs in svPPA and lvPPA is mainly based on studies with a priori knowledge of PPA syndrome diagnosis. This fully blinded retrospective study aims to provide data on the prevalence of all types of MSDs in a large sample of German-speaking patients with different subtypes of PPA. Method: Two raters, blinded for PPA subtype, independently evaluated connected speech samples for MSD syndrome and severity from 161 patients diagnosed with nfvPPA, svPPA or lvPPA in the database of the German Consortium of Frontotemporal Lobar Degeneration (FTLDc). In case of disagreement, a third experienced rater re-evaluated the speech samples, followed by a consensus procedure. Consensus was reached for 160 patients (74 nfvPPA, 49 svPPA, 37 lvPPA). Main results: Across all PPA syndromes, 43.8% of the patients showed MSDs. Patients with nfvPPA demonstrated the highest proportion of MSDs (62.2%), but MSDs were also identified in svPPA (26.5%) and lvPPA (29.7%), respectively. Overall, dysarthria was the most common class of MSDs, followed by apraxia of speech. In addition, we identified speech abnormalities presenting as “syllabic speech”, “dysfluent speech”, and “adynamic speech”. Discussion: Our study confirmed MSDs as frequently occurring in PPA. The study also confirmed MSDs to be most common in patients with nfvPPA. However, MSDs were also found in substantial proportions of patients with svPPA and lvPPA. Furthermore, our study identified speech motor deficits that have not received attention in previous studies on PPA. The results are discussed against the background of the existing literature on MSDs in PPA, including theoretical considerations of the neuroanatomical conditions described for each of the different subtypes of PPA.
CRIS-Team Scopus Importer:2021-06-11
Keywords: Apraxia of speech; Dysarthria; Motor speech disorders; Primary progressive aphasia (PPA)

mRNA expression of SMPD1 encoding acid sphingomyelinase decreases upon antidepressant treatment - Rhein, Cosima; Zoicas, Iulia; Marx, Lena M.; Zeitler, Stefanie; Hepp, Tobias; von Zimmermann, Claudia; Mühle, Christiane; Richter-Schmidinger, Tanja; Lenz, Bernd; Erim, Yesim; Reichel, Martin; Gulbins, Erich; et al. (International Journal of Molecular Sciences, 2021)
Major depressive disorder (MDD) is a severe psychiatric condition with key symptoms of low mood and lack of motivation, joy, and pleasure. Recently, the acid sphingomyelinase (ASM)/ceramide system has been implicated in the pathogenesis of MDD. ASM is a lysosomal glycoprotein that catalyzes the hydrolysis of sphingomyelin, an abundant component of membranes, into the bioactive sphingolipid ceramide, which impacts signaling pathways. ASM activity is inhibited by several common antidepressant drugs. Human and murine studies have confirmed that increased ASM activity and ceramide levels are correlated with MDD. To define a molecular marker for treatment monitoring, we investigated the mRNA expression of SMPD1, which encodes ASM, in primary cell culture models, a mouse study, and a human study with untreated MDD patients before and after antidepressive treatment. Our cell culture study showed that a common antidepressant inhibited ASM activity at the enzymatic level and also at the transcriptional level. In a genetically modified mouse line with depressive-like behavior, Smpd1 mRNA expression in dorsal hippocampal tissue was significantly decreased after treatment with a common antidepressant. The large human study showed that SMPD1 mRNA expression in untreated MDD patients decreased significantly after antidepressive treatment. This translational study shows that SMPD1 mRNA expression could serve as a molecular marker for treatment and adherence monitoring of MDD.
CRIS-Team Scopus Importer:2021-06-04
Keywords: Acid sphingomyelinase; Amitripty-line; Antidepressants; Biomarker; FIASMA; Fluoxetine; Major depressive disorder; SMPD1

Multi-antigen imaging reveals inflammatory dc, adam17 and neprilysin as effectors in keloid formation - Rath, Mathias; Pitiot, Alain; Kirr, Michael; Fröhlich, Waltraud; Plosnita, Bianca; Schliep, Stefan; Bauerschmitz, Jürgen; Baur, Andreas; Ostalecki, Christian (International Journal of Molecular Sciences, 2021)
Keloid is an aberrant scarring process of the skin, characterized by excessive extracellular matrix synthesis and deposition. The pathogenesis of this prevalent cutaneous disorder is not fully understood; however, a persistent inflammatory process is observed. To obtain more insight into this process, we analyzed lesional, perilesional and healthy tissue using multi-antigen-analysis (MAA) in conjunction with a data mining approach. Here, we demonstrate that monocyte-derived inflammatory dendritic cells (CD1a+, CD11c+, CD14+) and activated CD4+ T lymphocytes (CD45 RO+) dominated the immune infiltration in keloids while associating with fibroblasts. In perilesional tissue, precursor immune cells were dominant in the perivascular area, suggesting that they were attracted by an immune process, potentially in the lesional area. Supporting this hypothesis, only in keloid lesions, high levels of ADAM10/17 and Neprilysin (CD10) were observed in both fibroblasts and leukocytes. The spatial proximity of these two cell types, which could be confirmed by image analysis only in lesional tissue, could be a potential factor leading to the activation of fibroblasts. Our findings provide new insight into the pathogenesis of keloid formation and reveal metalloproteinases as a target for therapeutical intervention.
CRIS-Team Scopus Importer:2021-09-10
Keywords: Dendritic cells; Multiplex imaging; Proteases; Scar; Single-cell analysis; Tumor biology; Tumor microenvironment

Multicenter Validation of the max-ICH Score in Intracerebral Hemorrhage - Sembill, Jochen; Castello, Juan P.; Sprügel, Maximilian; Gerner, Stefan; Lücking, Hannes; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen; Biffi, Alessandro; Kuramatsu, Joji; Hölter, Philip (Annals of Neurology, 2020)
Objective: Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to determine whether the max-ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long-term outcomes after ICH. Methods: This multicenter validation study compared the prognostication of the max-ICH Score versus the ICH Score regarding diagnostic accuracy (discrimination and calibration) and clinical utility using decision curve analysis. We performed a joint investigation of individual participant data of consecutive spontaneous ICH patients (n = 4,677) from 2 retrospective German-wide studies (RETRACE I + II; anticoagulation-associated ICH only) conducted at 22 participating centers, one German prospective single-center study (UKER-ICH; nonanticoagulation-associated ICH only), and 1 US-based prospective longitudinal single-center study (MGH; both anticoagulation- and nonanticoagulation-associated ICH), treated between January 2006 and December 2015. Results: Of 4,677 included ICH patients, 1,017 (21.7%) were affected by ECL (German cohort: 15.6% [440 of 2,377]; MGH: 31.0% [577 of 1,283]). Validation of long-term functional outcome prognostication by the max-ICH Score provided good and superior discrimination in patients without ECL compared with the ICH Score (area under the receiver operating curve [AUROC], German cohort: 0.81 [0.78–0.83] vs 0.74 [0.72–0.77], p < 0.01; MGH: 0.85 [0.81–0.89] vs 0.78 [0.74–0.82], p < 0.01), and for the entire cohort (AUROC, German cohort: 0.84 [0.82–0.86] vs 0.80 [0.77–0.82], p < 0.01; MGH: 0.83 [0.81–0.85] vs 0.77 [0.75–0.79], p < 0.01). Both scores showed no evidence of poor calibration. The clinical utility investigated by decision curve analysis showed, at high threshold probabilities (0.8, aiming to avoid false-positive poor outcome attribution), that the max-ICH Score provided a clinical net benefit compared with the ICH Score (14.1 vs 2.1 net predicted poor outcomes per 100 patients). Interpretation: The max-ICH Score provides valid and improved prognostication of functional outcome after ICH. The associated clinical net benefit in minimizing false poor outcome attribution might potentially prevent unwarranted care limitations in patients with ICH. ANN NEUROL 2020.
CRIS-Team Scopus Importer:2020-12-25

Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging - Lampe, Leonie; Huppertz, Hans Jürgen; Anderl-Straub, Sarah; Albrecht, Franziska; Ballarini, Tommaso; Bisenius, Sandrine; Mueller, Karsten; Niehaus, Sebastian; Fassbender, Klaus; Fliessbach, Klaus; Jahn, Holger; Kornhuber, Johannes; et al. (NeuroImage: Clinical, 2023)
Introduction: Dementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI). Methods: Atlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimer's disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification). Results: The binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration. Discussion: Results suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimer's disease.
CRIS-Team Scopus Importer:2023-01-20
Keywords: Dementia; Diagnosis; Machine learning; MRI; Neurodegeneration; Volumetry

Multidisciplinary Late Effects Clinics for Childhood Cancer Survivors in Germany - a Two-Center Study - Gebauer, Judith; Rieken, Sarah; Schuster, Sonja; Hahn, Birgit; Gebauer, Niklas; Meidenbauer, Norbert; Brabant, Georg; Metzler, Markus; Langer, Thorsten (Oncology Research and Treatment, 2018)
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Multivariate diagnostic approaches in Frontotemporal lobar degeneration - Data from the german FTLDc - Straub, S.; Schroeter, M. L.; Diehl-Schmid, J.; Danek, A.; Von Arnim, C.; Bertram, L.; Einsiedler, B.; Fassbender, K.; Feneberg, E.; Fliessbach, K.; Foerstl, H.; Huppertz, H-J; et al. (2016)
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MuSK-antibodies are associated with worse outcome in myasthenic crisis requiring mechanical ventilation - Konig, Nicole; Stetefeld, Henning R.; Dohmen, Christian; Mergenthaler, Philipp; Kohler, Siegfried; Schonenberger, Silvia; Bosel, Julian; Lee, De-Hyung; Gerner, Stefan; Huttner, Hagen; Schneider, Hauke; Reichmann, Heinz; et al. (Journal of Neurology, 2021)
Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Muscle-specific kinase-antibodies (MuSK-ABs) are detected in 6% of MG, but data on outcome of MuSK-MCs are still lacking. We made a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody positive MG (AchR-MG) or MuSK-MG between 2006 and 2015 in a retrospective German multicenter study. We identified 19 MuSK-AB associated MCs in 15 patients and 161 MCs in 144 patients with AchR-ABs only. In contrast to patients with AchR-AB, MuSK-AB patients were more often female (p = 0.05, OR = 2.74) and classified as Myasthenia Gravis Foundation of America-class IV before crisis (p = 0.04, OR = 3.25). MuSK-AB patients suffer more often from multiple chronic disease (p = 0.016, OR = 4.87) and were treated more invasively in terms of plasma exchanging therapies (not significant). The number of days of mechanical ventilation (MV) (43.0 ± 53.1 vs. 17.4 ± 18; p < 0.0001), days on an intensive care unit (ICU) (45.3 ± 49.5 vs. 21.2 ± 19.7; p < 0.0001), and hospital-length of stay (LOS) (55.9 ± 47.6 vs. 28.8 ± 20.9 days; p < 0.0001) were significantly increased in MuSK-MC. Remarkable is that these changes were mainly due to patients with MusK-ABs only, whereas patients’ outcome with both antibodies was similar to AchR-MCs. Furthermore, our data showed a shortened duration of MV after treatment with plasma exchanging therapies compared to treatment with intravenous immunoglobulin in MuSK-MCs. We conclude that MuSK-AB-status is associated with a longer need of MV, ICU-LOS, and hospital-LOS in MC, and therefore recommend early initiation of a disease-specific therapy.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Antibody status; Autoimmune diseases; MuSK-antibodies; Myasthenia gravis; Myasthenic crisis; Outcome

Nanoscopical Analysis Reveals an Orderly Arrangement of the Presynaptic Scaffold Protein Bassoon at the Golgi-Apparatus - Ghelani, Tina; Montenegro-Venegas, Carolina; Fejtová, Anna; Dresbach, Thomas (Frontiers in Molecular Neuroscience, 2021)
Bassoon is a core scaffold protein of the presynaptic active zone. In brain synapses, the C-terminus of Bassoon is oriented toward the plasma membrane and its N-terminus is oriented toward synaptic vesicles. At the Golgi-apparatus, Bassoon is thought to assemble active zone precursor structures, but whether it is arranged in an orderly fashion is unknown. Understanding the topology of this large scaffold protein is important for models of active zone biogenesis. Using stimulated emission depletion nanoscopy in cultured hippocampal neurons, we found that an N-terminal intramolecular tag of recombinant Bassoon, but not C-terminal tag, colocalized with markers of the trans-Golgi network (TGN). The N-terminus of Bassoon was located between 48 and 69 nm away from TGN38, while its C-terminus was located between 100 and 115 nm away from TGN38. Sequences within the first 95 amino acids of Bassoon were required for this arrangement. Our results indicate that, at the Golgi-apparatus, Bassoon is oriented with its N-terminus toward and its C-terminus away from the trans Golgi network membrane. Moreover, they suggest that Bassoon is an extended molecule at the trans Golgi network with the distance between amino acids 97 and 3,938, estimated to be between 46 and 52 nm. Our data are consistent with a model, in which the N-terminus of Bassoon binds to the membranes of the trans-Golgi network, while the C-terminus associates with active zone components, thus reflecting the topographic arrangement characteristic of synapses also at the Golgi-apparatus.
CRIS-Team Scopus Importer:2021-12-10
Keywords: Bassoon; Golgi; STED; synapse assembly; synaptogenesis

Native language group therapy with female migrants from Turkey - Erim, Yesim (Gruppenpsychotherapie und Gruppendynamik, 2001)

Need for Care in Old Age: Characterization of Informal Caregivers and the Care Situation with Regard to Care Levels in Home Care Pflegebedürftigkeit im Alter: Angehörigen- und Versorgungssituation im Zusammenhang mit den Pflegegraden bei häuslicher Pflege - Keck, Antonia; Pendergrass, Anna; Grässel, Elmar (Gesundheitswesen, Supplement, 2024)
Objective In Germany, people in need of care can be supported by benefits from care insurance. Prerequisite is an official assessment of the need for care, which is carried out by assigning care levels (1 to 5) according to the Second Care Strengthening Act. One of the reasons for introducing care levels was to pay more attention to the needs of people with dementia. In this article, characterization of care levels were based on characteristics of care recipients, their relatives, and the care situation. The aim was to map the current state of health care and providing practical suggestions to improve health care. Methods Data was collected as part of the cross-sectional study “Benefits of being a caregiver” by a written survey of informal caregivers throughout Bavaria on aspects of the caregiving situation as well as on current and desired future use of 15 care services. To compare care levels, group differences were analyzed using χ2-tests and one-factor analysis of variance. The effect size measures odds ratio and Cohen's d were reported for significant group differences comparing care levels 1 and 4. The sample consisted of 958 cases of people in need of care aged 65 and above. Results The proportion of people with dementia increased significantly with care level. For informal caregivers, subjective burden, functional coping strategies, and the caregiving motive of not wanting to place the care recipient in a nursing home increased with care level. Informal caregivers of those with higher care levels spent significantly more time on supporting activities of daily living and supervision; they received more informal help, and more often lived together with the care recipient in a household. For 9 of the 15 care services surveyed (e. g. 24-h care), current use increased significantly with increasing care level. However, we recorded a low overall utilization rate of care services across all care levels (M= 2.20; SD= 1.90). Conclusions As a result of the Second Care Strengthening Act, people with dementia get good access to care insurance benefits. The increasing amount of time required for assisting in activities of daily living and supervision is reflected by care levels. Despite the increasing caregiving burden, care services are rarely used. Therefore, we recommend that measures to increase the use of support and counselling services be expanded.
CRIS-Team Scopus Importer:2024-03-08
Keywords: care levels; geriatric care; informal caregivers; levels of care; Need for care

Negative pressure wound therapy for seroma prevention and surgical incision treatment in spinal fracture care - Nordmeyer, Matthias; Pauser, Johannes; Biber, Roland; Jantsch, Jonathan; Lehrl, Siegfried; Kopschina, Carsten; Rapke, Christian; Bail, Hermann J.; Forst, Raimund; Brem, Matthias H. (International Wound Journal, 2015)
To evaluate the clinical use and economic aspects of negative pressure wound therapy (NPWT) after dorsal stabilisation of spinal fractures. This study is a prospective randomised evaluation of NPWT in patients with large surgical wounds after surgical stabilisation of spinal fractures by internal fixation. Patients were randomised to either standard wound dressing treatment (group A) or NPWT (group B). The wound area was examined by ultrasound to measure seroma volumes in both groups on the 5th and 10th day after surgery. Furthermore, data on economic aspects such as nursing time for wound care and material used for wound dressing were evaluated. A total of 20 patients (10 in each group) were enrolled. Throughout the whole study, mean seroma volume was significantly higher in group A than that in group B (day 5: 1·9 ml versus 0 ml; P = 0·0007; day 10: 1·6 ml versus 0·5 ml; P <0·024). Furthermore, patients of group A required more wound care time (group A: 31 ± 10 minutes; group B 13·8 ± 6 minutes; P = 0·0005) and more number of compresses (total number; group A 35 ± 15; group B 11 ± 3; P = 0·0376). NPWT reduced the development of postoperative seroma, reduced nursing time and reduced material required for wound care.
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Neural basis of reward anticipation and its genetic determinants - Jia, Tianye; Macare, Christine; Desrivieres, Sylvane; Gonzalez, Dante A.; Tao, Chenyang; Ji, Xiaoxi; Ruggeri, Barbara; Nees, Frauke; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Bromberg, Uli; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2016)
Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.
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Neural mechanisms of perceptive and affective processing of body stimuli in anorexia nervosa – are there developmental effects? - Horndasch, Stefanie; Rösch, Julie; Kratz, Oliver; Vogel, Anne; Heinrich, Hartmut; Graap, Holmer; Moll, Gunther; Dörfler, Arnd; Forster, Clemens (Psychiatry Research, 2020)
Different components of body image processing seem to be reflected by different neural mechanisms. A core symptom of Anorexia nervosa (AN) is a disturbance of body image with correlates found on a neural level. The present study focuses on the neural processing of visual body stimuli of different weight categories in adolescent and adult AN patients. Thirty-three adolescents aged 12–18 years (15 AN patients, 18 control participants) and 36 adult women (19 AN patients, 17 control participants) underwent functional magnetic resonance imaging (fMRI) while performing a perceptive and an affective body image task involving photographic stimuli of women belonging to different BMI categories. Differential effects on activation, depending on the BMI of the women shown in the pictures, were found in frontal brain regions, the thalamus, the caudate and the fusiform gyrus. Group effects differentiating between AN patients and control participants were seen mainly in the caudate and insula. No significant developmental effect was seen. During a perceptive task, diminished activation of regions involved in perceptive and evaluative functions as well as emotional reasoning was seen in AN. During an affective task there was a tendency towards activation differences reflecting reduced ability of size estimation and impaired integration of visual and body perception with emotions.
CRIS-Team Scopus Importer:2020-03-10
Keywords: Adolescence; Body; Eating disorders; fMRI

Neural processing of food and emotional stimuli in adolescent and adult anorexia nervosa patients - Horndasch, Stefanie; Roesch, Julie; Forster, Clemens; Dörfler, Arnd; Lindsiepe, Silja; Heinrich, Hartmut; Graap, Holmer; Moll, Gunther; Kratz, Oliver (PLoS ONE, 2018)
BACKGROUND: A constant preoccupation with food and restrictive eating are main symptoms of anorexia nervosa (AN). Imaging studies revealed aberrant neural activation patterns in brain regions processing hedonic and reward reactions as well as-potentially aversive-emotions. An imbalance between so called "bottom-up" and "top-down" control areas is discussed. The present study is focusing on neural processing of disease-specific food stimuli and emotional stimuli and its developmental course in adolescent and adult AN patients and could offer new insight into differential mechanisms underlying shorter or more chronic disease. METHODS: 33 adolescents aged 12-18 years (15 AN patients, 18 control participants) and 32 adult women (16 AN patients, 16 control participants) underwent functional magnetic resonance imaging (fMRI, 3T high-field scanner) while watching pictures of high and low-calorie food and affective stimuli. Afterwards, they rated subjective valence of each picture. FMRI data analysis was performed using a region of interest based approach. RESULTS: Pictures of high-calorie food items were rated more negatively by AN patients. Differences in activation between patients and controls were found in "bottom up" and "top down" control areas for food stimuli and in several emotion processing regions for affective stimuli which were more pronounced in adolescents than in adults. CONCLUSION: A differential pattern was seen for food stimuli compared to generally emotion eliciting stimuli. Adolescents with AN show reduced processing of affective stimuli and enhanced activation of regions involved in "bottom up" reward processing and "top down" control as well as the insula with regard to food stimuli with a focus on brain regions which underlie changes during adolescent development. In adults less clear and less specific activation differences were present, pointing towards a high impact that regions undergoing maturation might have on AN symptoms.
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Neuroadaptations to antipsychotic drugs: Insights from pre-clinical and human post-mortem studies - Amato, Davide; Beasley, Clare L.; Hahn, Margaret K.; Vernon, Anthony C. (Neuroscience and Biobehavioral Reviews, 2017)
Antipsychotic drugs, all of which block the dopamine D2 receptor to a greater or lesser extent, are the mainstay for the pharmacological treatment of schizophrenia. Engaging in a deeper understanding of how antipsychotics act on the brain and body, at the cellular, molecular and physiological level is vital to comprehend both the beneficial and potentially harmful actions of these medications and stimulate development of novel therapeutics. To address this, we review recent advances in our understanding of neuroadaptations to antipsychotics, focusing on (1) treatment efficacy, (2) impact on brain volume and (3) evidence from human post-mortem studies that attempt to dissect neuropathological effects of antipsychotic drugs from organic schizophrenia neurobiology and (4) cardio-metabolic side effects. Our aim is to stimulate discussion on these highly clinically relevant topics and consider how we might use current and evolving knowledge and new methodologies in the fields of neuropharmacology and neuroscience, to advance our understanding of the long-term impact of antipsychotic treatment. Ultimately, this may inform the clinical use of these drugs.
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Neuroanatomical correlates of intelligence in healthy young adults: the role of basal ganglia volume - Rhein, Cosima; Mühle, Christiane; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Dörfler, Arnd; Kornhuber, Johannes (PLoS ONE, 2014)
In neuropsychiatric diseases with basal ganglia involvement, higher cognitive functions are often impaired. In this exploratory study, we examined healthy young adults to gain detailed insight into the relationship between basal ganglia volume and cognitive abilities under non-pathological conditions.We investigated 137 healthy adults that were between the ages of 21 and 35 years with similar educational backgrounds. Magnetic resonance imaging (MRI) was performed, and volumes of basal ganglia nuclei in both hemispheres were calculated using FreeSurfer software. The cognitive assessment consisted of verbal, numeric and figural aspects of intelligence for either the fluid or the crystallised intelligence factor using the intelligence test Intelligenz-Struktur-Test (I-S-T 2000 R). Our data revealed significant correlations of the caudate nucleus and pallidum volumes with figural and numeric aspects of intelligence, but not with verbal intelligence. Interestingly, figural intelligence associations were dependent on sex and intelligence factor; in females, the pallidum volumes were correlated with crystallised figural intelligence (r = 0.372, p = 0.01), whereas in males, the caudate volumes were correlated with fluid figural intelligence (r = 0.507, p = 0.01). Numeric intelligence was correlated with right-lateralised caudate nucleus volumes for both females and males, but only for crystallised intelligence (r = 0.306, p = 0.04 and r = 0.459, p = 0.04, respectively). The associations were not mediated by prefrontal cortical subfield volumes when controlling with partial correlation analyses.The findings of our exploratory analysis indicate that figural and numeric intelligence aspects, but not verbal aspects, are strongly associated with basal ganglia volumes. Unlike numeric intelligence, the type of figural intelligence appears to be related to distinct basal ganglia nuclei in a sex-specific manner. Subcortical brain structures thus may contribute substantially to cognitive performance.
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Neurobiology of Kratom and its main alkaloid mitragynine - Suhaimi, Farah W.; Yusoff, Nurul H. M.; Hassan, Rahimah; Mansor, Sharif M.; Navaratnam, Visweswaran; Müller, Christian P.; Hassan, Zurina (Brain Research Bulletin, 2016)
Kratom or its main alkaloid, mitragynine is derived from the plant Mitragyna speciosa Korth which is indigenous to Southeast Asian countries. This substance has become widely available in other countries like Europe and United States due to its opium- and coca-like effects. In this article, we have reviewed available reports on mitragynine and other M. speciosa extracts. M. speciosa has been proven to have a rewarding effect and is effective in alleviating the morphine and ethanol withdrawal effects. However, studies in human revealed that prolonged consumption of this plant led to dependence and tolerance while cessation caused a series of aversive withdrawal symptoms. Findings also showed that M. speciosa extracts possess antinociceptive, anti-inflammatory, anti-depressant, and muscle relaxant properties. Available evidence further supports the adverse effects of M. speciosa preparations, mitragynine on cognition. Pharmacological activities are mainly mediated via opioid receptors as well as neuronal Ca(2+) channels, expression of cAMP and CREB protein and via descending monoaminergic system. Physicochemical properties of mitragynine have been documented which may further explain the variation in pharmacological responses. In summary, current researchs on its main indole alkaloid, mitragynine suggest both therapeutic and addictive potential but further research on its molecular effects is needed.
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Neurochemical dementia diagnostics: Assays in CSF and blood - Lewczuk, Piotr; Hornegger, Joachim; Zimmermann, Rüdiger; Otto, Markus; Wiltfang, Jens; Kornhuber, Johannes (European archives of psychiatry and clinical neuroscience, 2008)
In this review, current neurochemical dementia diagnostics (NDD) procedures are presented with a focus on biomarkers in the cerebrospinal fluid (CSF) and blood: amyloid β peptides, tau protein, and its phosphorylated form (pTau). CSF analysis is an increasingly important tool for early and differential diagnosis of dementia syndromes. Although lumbar puncture is a mildly invasive procedure with a low incidence of complications, establishing blood assays capable of reliably measuring NDD biomarkers is an aim of several studies worldwide. © 2008 Springer.

Neurofeedback bei Kindern mit ADHS - Welche Wirkungen sind zu erwarten? Stand der Forschung und Anregungen für die Praxis - Strehl, Ute; Heinrich, Hartmut; Rothenberger, A.; Gevensleben, H. (Pädiatrische Praxis, 2019)
EEG neurofeedback is a possible complementary procedure for the treatment of ADHD. It is based on observations that children with ADHD exhibit physiologically hypoarousal of brain activity. Standard protocols in the frequency band (theta/beta, SMR) or event-related brain activity (Slow Coetical Potentials, SCP) have been investigated in a number of studies. They suggest that NF, using standard protocols and a neurobehavioral approach, is a specific, effective and evidence-based component for the treatment of children with ADHD. Open questions, which aim at a better understanding of the mechanisms of action and in particular at the optimisation and individualisation of training, must be pursued further.
CRIS-Team Scopus Importer:2021-04-20
Keywords: ADHD; Efficacy; Methodical basis; Neurofeedback; Practical application

Neurofeedback in ADHD: further pieces of the puzzle - Gevensleben, Holger; Kleemeyer, Maike; Rothenberger, Lillian Geza; Studer, Petra; Flaig-Roehr, Andrea; Moll, Gunther; Rothenberger, Aribert; Heinrich, Hartmut (Brain Topography, 2014)
Among the different neuromodulation techniques, neurofeedback (NF) is gaining increasing interest in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). In this article, a methodological framework is summarised considering the training as a neuro-behavioural treatment. Randomised controlled trials are selectively reviewed. Results from two smaller-scale studies are presented with the first study comprising a tomographic analysis over the course of a slow cortical potential (SCP) training and a correlational analysis of regulation skills and clinical outcome in children with ADHD. In the second study, ADHD-related behaviour was studied in children with tic disorder who either conducted a SCP training or a theta/low-beta (12-15 Hz) training (single-blind, randomised design). Both studies provide further evidence for the specificity of NF effects in ADHD. Based on these findings, a refined model of the mechanisms contributing to the efficacy of SCP training is developed. Despite a number of open questions concerning core mechanisms, moderators and mediators, NF (theta/beta and SCP) training seems to be on its way to become a valuable and ethically acceptable module in the treatment of children with ADHD.
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Neurofeedback in attention-deficit/hyperactivity disorder - different models, different ways of application - Gevensleben, Holger; Moll, Gunther; Rothenberger, Aribert; Heinrich, Hartmut (Frontiers in Human Neuroscience, 2014)
In children with attention-deficit/hyperactivity disorder (ADHD), different neurofeedback (NF) protocols have been applied, with the most prominent differentiation between EEG frequency-band (e.g., theta/beta) training and training of slow cortical potentials (SCPs). However, beyond distinctions between such basic NF variables, there are also competing assumptions about mechanisms of action (e.g., acquisition of regulation capability, generalization to daily life behavior). In the present article, we provide a framework for NF models and suppose two hypothetical models, which we call "conditioning-and-repairing model" and "skill-acquisition model," reflecting extreme poles within this framework. We argue that the underlying model has an impact not only on how NF is applied but also on the selection of evaluation strategies and suggest using evaluation strategies beyond beaten paths of pharmacological research. Reflecting available studies, we address to what extent different views are supported by empirical data. We hypothesize that different models may hold true depending on the processes and behaviors to be addressed by a certain NF protocol. For example, the skill-acquisition model is supported by recent findings as an adequate explanatory framework for the mechanisms of action of SCP training in ADHD. In conclusion, evaluation and interpretation of NF trials in ADHD should be based on the underlying model and the way training is applied, which, in turn, should be stated explicitly in study reports.
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Neurofeedback of slow cortical potentials: neural mechanisms and feasibility of a placebo-controlled design in healthy adults - Gevensleben, Holger; Albrecht, Bjoern; Luetcke, Henry; Auer, Tibor; Dewiputri, Wan Ilma; Schweizer, Renate; Moll, Gunther; Heinrich, Hartmut; Rothenberger, Aribert (Frontiers in Human Neuroscience, 2014)
To elucidate basic mechanisms underlying neurofeedback we investigated neural mechanisms of training of slow cortical potentials (SCPs) by considering EEG- and fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo-controlled design in NF research based on regulation performance during treatment sessions and self-assessment of the participants. Twenty healthy adults participated in 16 sessions of SCPs training: 9 participants received regular SCP training, 11 participants received sham feedback. At three time points (pre, intermediate, post) fMRI and EEG/ERP-measurements were conducted during a continuous performance test (CPT). Performance-data during the sessions (regulation performance) in the treatment group and the placebo group were analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement of the CNV (electrode Cz) at the intermediate assessment, followed by a decrease back to baseline at the post-treatment assessment. In contrast, in the placebo group a continuous but smaller increase of the CNV could be obtained from pre to post assessment. The increase of the CNV in the SCP group at intermediate testing was superior to the enhancement in the placebo group. The changes of the CNV were accompanied by a continuous improvement in the test performance of the CPT from pre to intermediate to post assessment comparable in both groups. The change of the CNV in the SCP group is interpreted as an indicator of neural plasticity and efficiency while an increase of the CNV in the placebo group might reflect learning and improved timing due to the frequent task repetition. In the fMRI analysis evidence was obtained for neuronal plasticity. After regular SCP neurofeedback activation in the posterior parietal cortex decreased from the pre- to the intermediate measurement and increased again in the post measurement, inversely following the U-shaped increase and decrease of the tCNV EEG amplitude in the SCP-trained group. Furthermore, we found a localized increase of activity in the anterior cingulate cortex (ACC). Analyses of the estimation of treatment assignment by the participants indicate feasibility of blinding. Participants could not assess treatment assignment confidently. Participants of the SCP-group improved regulation capability during treatment sessions (in contrast to the participants of the placebo-group), although regulation capability appeared to be instable, presumably due to diminished confidence in the training (SCP- or sham-training). Our results indicate that SCP training in healthy adults might lead to functional changes in neuronal circuits serving cognitive preparation even after a limited number of sessions.
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Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias - Steinacker, Petra; Semler, Elisa; Anderl-Straub, Sarah; Diehl-Schmid, Janine; Schroeter, Matthias L.; Uttner, Ingo; Foerstl, Hans; Landwehrmeyer, Bernhard; Von Arnim, Christine A. F.; Kassubek, Jan; Oeckl, Patrick; Huppertz, Hans-Juergen; et al. (Neurology, 2017)
OBJECTIVE: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. METHODS: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), β-amyloid (Aβ1-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy. RESULTS: Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Aβ1-42achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA. CONCLUSIONS: Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with PPA, blood levels of NF-L can distinguish the logopenic variant from the nonfluent/agrammatic and semantic variants.
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Neurofilament light chain protein concentration in CSF and atrophy are correlated in bvFTD patients - Data from the multicentric FTLD consortium's study - Meyer, S.; Mueller, K.; Bisenius, S.; Diehl-Schmid, J.; Foerstl, H.; Fassbender, K.; Kassubek, Jan; Landwehrmeyer, B.; Ludolph, A. C.; Kornhuber, Johannes; Prudlo, J.; Schneider, A.; et al. (2016)
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Neuroimaging of smell and taste - Olofsson, Jonas K.; Freiherr, Jessica (Handbook of Clinical Neurology, 2019)
The senses of taste and smell developed early in evolution and are of high ecological and clinical relevance in humans. Chemosensory systems function, in large part, as hazard avoidance systems, thereby ensuring survival. Moreover, they play a critical role in nutrition and in determining the flavor of foods and beverages. Their dysfunction has been shown to be a key element of early stages of a number of diseases, including Alzheimer's and Parkinson's diseases. Advanced neuroimaging methods provide a unique means for understanding, in vivo, neural and psychological processing of smell, taste, and flavor, and how diseases can impact such processing. This chapter provides, from a neuroimaging perspective, a comprehensive overview of the anatomy and physiology involved in the odor and taste processing in the central nervous system. Some methodological challenges associated with chemosensory neuroimaging research are discussed. Multisensory integration, the mechanisms that enable holistic sensory experiences, is emphasized.
CRIS-Team Scopus Importer:2019-10-15
Keywords: Attention; Flavor; Functional imaging; Gustation; Gustometer; Multisensory integration; Odor; Olfaction; Olfactometer; Reward

Neuropeptide y as alternative pharmacotherapy for antidepressant-resistant social fear - Kornhuber, Johannes; Zoicas, Iulia (International Journal of Molecular Sciences, 2020)
In many social anxiety disorder (SAD) patients, the efficacy of antidepressant therapy is unsatisfactory. Here, we investigated whether mice deficient for the lysosomal glycoprotein acid sphingomyelinase (ASM−/−) represent an appropriate tool to study antidepressant-resistant social fear. We also investigated whether neuropeptide Y (NPY) reduces this antidepressant-resistant social fear in ASM−/− mice, given that NPY reduced social fear in a mouse model of SAD, namely social fear conditioning (SFC). We show that neither chronic paroxetine nor chronic amitriptyline administration via drinking water were successful in reducing SFC-induced social fear in ASM−/− mice, while the same treatment reduced social fear in ASM+/− mice and completely reversed social fear in ASM+/+ mice. This indicates that the antidepressants paroxetine and amitriptyline reduce social fear via the ASM-ceramide system and that ASM−/− mice represent an appropriate tool to study antidepressant-resistant social fear. The intracerebroventricular administration of NPY, on the other hand, reduced social fear in ASM−/− mice, suggesting that NPY might represent an alternative pharmacotherapy for antidepressant-resistant social fear. These results suggest that medication strategies aimed at increasing brain NPY concentrations might improve symptoms of social fear in SAD patients who fail to respond to antidepressant treatments.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Amitriptyline; Fear expression; Fear extinction; NPY; Paroxetine; Social anxiety; Social fear; Social investigation; SSRI; Tricyclic antidepressants

Neuropeptide Y prolongs non-social memory and differentially affects acquisition, consolidation, and retrieval of non-social and social memory in male mice - Kornhuber, Johannes; Zoicas, Iulia (Scientific Reports, 2017)
Neuropeptide Y (NPY) and its receptors (especially Y1, Y2, and Y5) are highly expressed in brain regions involved in learning and memory processes. Accordingly, NPY was shown to modulate cognitive functions in rodents. Here, we investigated possible memory-enhancing effects of NPY and determined the role of the NPY system in the acquisition, consolidation, and retrieval of non-social and social memory in mice, using the object and social discrimination tests, respectively. Intracerebroventricular (icv) infusion of NPY (1 nmol/2 µl) prolonged retention of non-social (object) memory, but not of social memory. This effect was blocked by the Y1 receptor antagonist BIBO3304 trifluoroacetate (2 nmol/2 µl), but not by the Y2 receptor antagonist BIIE0246 (2 nmol/2 µl). While icv infusion of NPY did not affect the acquisition, consolidation, and retrieval of non-social and social memory, icv infusion of BIBO3304 trifluoroacetate and BIIE0246 blocked the consolidation of non-social memory and the retrieval of both non-social and social memory. This study suggests that NPY has memory-enhancing effects in a non-social context by specifically acting on Y1 receptors. It further suggests that the central NPY system exerts differential effects on the sequential phases of non-social and social memory.
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Neuropeptide Y prolongs non-social memory in a brain region- and receptor-specific way in male mice - Kornhuber, Johannes; Zoicas, Iulia (Neuropharmacology, 2020)
Neuropeptide Y (NPY) and its receptors are highly expressed in brain regions involved in learning and memory processes. We have previously shown that intracerebroventricular administration of NPY prolongs the retention of non-social memory in the object discrimination test. Here, we aimed to identify the brain regions which mediate these memory-enhancing effects of NPY. We show that NPY (0.1 nmol/0.2 μl/side) prolongs retention of non-social memory when administered into the dorsolateral septum (DLS) and medial amygdala (MeA), but not when administered into the dorsal hippocampus, central amygdala and basolateral amygdala. In the DLS, the effects of NPY were blocked by the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 μl/side), but not by the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 μl/side). In the MeA, on the other hand, BIIE0246, but not BIBO3304 trifluoroacetate blocked the effects of NPY. This study demonstrates that NPY exerts Y1 receptor-mediated memory-enhancing effects in the DLS and Y2 receptor-mediated memory-enhancing effects in the MeA, and suggests that distinct brain regions and receptor subtypes are recruited to mediate the effects of NPY on non-social memory.
CRIS-Team Scopus Importer:2020-06-30
Keywords: Discrimination memory; Local infusion; Memory retention; Object investigation; Object memory

Neuropeptide Y reduces expression of social fear via simultaneous activation of Y1 and Y2 receptors - Kornhuber, Johannes; Zoicas, Iulia (Journal of Psychopharmacology, 2019)
Background: Neuropeptide Y (NPY) has anxiolytic effects and facilitates extinction of cued and contextual fear in rodents, thereby acting as a resilience factor against exaggerated fear responses after adverse events. We investigated whether NPY influences acquisition, expression and extinction of social fear in a mouse model of social fear conditioning (SFC). Methods: NPY was administered intracerebroventricularly before SFC or before social fear extinction with or without prior administration of Y1 and/or Y2 receptor antagonists. Results: We show that NPY affects SFC-induced social fear in a time point-dependent manner. When administered before SFC, NPY did not affect acquisition, expression and extinction of social fear. However, when administered before social fear extinction, NPY reduced expression of social fear via simultaneous activation of Y1 and Y2 receptors. As such, neither the Y1 receptor antagonist BIBO3304 trifluoroacetate nor the Y2 receptor antagonist BIIE0246 was able to block the effects of NPY completely. However, when administered in combination, they completely blocked the effects of NPY on social fear expression. Conclusions: These findings have important clinical implications, as they suggest that although medication strategies aimed at increasing brain NPY activity are unlikely to prevent the formation of aversive memories after a traumatic social experience, they might improve the recovery from a traumatic social experience by reducing the expression of social fear.
CRIS-Team WoS Importer:2019-08-09

Neuropeptide Y Reduces Social Fear in Male Mice: Involvement of Y1 and Y2 Receptors in the Dorsolateral Septum and Central Amygdala - Kornhuber, Johannes; Zoicas, Iulia (International Journal of Molecular Sciences, 2021)
Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We previously showed that intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC) and localized these effects to the dorsolateral septum (DLS) and central amygdala (CeA). In the present study, we aimed to identify the receptor subtypes that mediate these local effects of NPY. We show that NPY (0.1 nmol/0.2 mu L/side) reduced the expression of SFC-induced social fear in a brain region- and receptor-specific manner in male mice. In the DLS, NPY reduced the expression of social fear by acting on Y2 receptors but not on Y1 receptors. As such, prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 mu L/side) but not the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 mu L/side) blocked the effects of NPY in the DLS. In the CeA, however, BIBO3304 trifluoroacetate but not BIIE0246 blocked the effects of NPY, suggesting that NPY reduced the expression of social fear by acting on Y1 receptors but not Y2 receptors within the CeA. This study suggests that at least two distinct receptor subtypes are differentially recruited in the DLS and CeA to mediate the effects of NPY on the expression of social fear.
CRIS-Team WoS Importer:2021-10-08

Neuropharmacology of light-induced locomotor activation - Amato, Davide; Pum, Martin E.; Groos, Dominik; Lauber, Andrea C.; Huston, Joseph P.; Carey, Robert J.; Silva, Maria A. De Souza; Müller, Christiane (Neuropharmacology, 2015)
Presentation of non-aversive light stimuli for several seconds was found to reliably induce locomotor activation and exploratory-like activity. Light-induced locomotor activity (LIA) can be considered a convenient simple model to study sensory-motor activation. LIA was previously shown to coincide with serotonergic and dopaminergic activation in specific cortical areas in freely moving and anesthetized animals. In the present study we explore the neuropharmacology of LIA using a receptor antagonist/agonist approach in rats. The non-selective 5-HT2-receptor antagonist ritanserin (1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. Selective antagonism of either the 5-HT2A-receptor by MDL 11,939 (0.1-0.4 mg/kg, i.p.), or the 5-HT2C-receptor by SDZ SER 082 (0.125-0.5 mg/kg, i.p.), alone or in combination, had no significant influence on LIA. Also the selective 5-HT1A-receptor antagonist, WAY 100635 (0.4 mg/kg, i.p.) did not affect LIA. Neither did the preferential dopamine D2-receptor antagonist, haloperidol (0.025-0.1 mg/kg, i.p.) nor the D2/D3-receptor agonist, quinpirole (0.025-0.5 mg/kg, i.p.) affect the expression of LIA. However, blocking the glutamatergic NMDA-receptor with phencyclidine (PCP, 1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. This effect was also observed with ketamine (10 mg/kg, i.p.). These findings suggest that serotonin and dopamine receptors abundantly expressed in the cortex do not mediate light-stimulus triggered locomotor activity. PCP and ketamine effects, however, suggest an important role of NMDA receptors in LIA.
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Neutral ceramidase is a marker for cognitive performance in rats and monkeys - Kalinichenko, Liubov; Wang, An Li; Mühle, Christiane; Abdel-Hafiz, Laila; Gulbins, Erich; Kornhuber, Johannes; Oliveira, André W.C.; Barros, Marilia; Huston, Joseph P.; Müller, Christian P. (Pharmacological Reports, 2020)
Background: Ceramides are lipid molecules determining cell integrity and intercellular signaling, and thus, involved in the pathogenesis of several psychiatric and neurodegenerative disorders. However, little is known about the role of particular enzymes of the ceramide metabolism in the mechanisms of normal behavioral plasticity. Here, we studied the contribution of neutral ceramidase (NC), one of the main enzymes mediating ceramide degradation, in the mechanisms of learning and memory in rats and non-human primates. Methods: Naïve Wistar rats and black tufted-ear marmosets (Callithrix penicillata) were tested in several tests for short- and long-term memory and then divided into groups with various memory performance. The activities of NC and acid ceramidase (AC) were measured in these animals. Additionally, anxiety and depression-like behavior and brain levels of monoamines were assessed in the rats. Results: We observed a predictive role of NC activity in the blood serum for superior performance of long-term object memory tasks in both species. A brain area analysis suggested that high NC activity in the ventral mesencephalon (VM) predicts better short-term memory performance in rats. High NC activity in the VM was also associated with worse long-term object memory, which might be mediated by an enhanced depression-like state and a monoaminergic imbalance. Conclusions: Altogether, these data suggest a role for NC in short- and long-term memory of various mammalian species. Serum activity of NC may possess a predictive role in the assessing the performance of certain types of memory.
CRIS-Team Scopus Importer:2020-09-25
Keywords: Ceramide; Memory; Neutral ceramidase; Non-human primates; Rats; Ventral mesencephalon

Neutral Sphingomyelinase Determines Sex-Specific Self-Regulation of Emotional State by Alcohol in Mice - Kalinichenko, Liubov; Ulrich, Franziska; Sauer, Christine; Meixner, Doris; Scholz, Jessica; Lacatasu, Laura; Valenta, Florian; Bauerle, Tobias; Kornhuber, Johannes; Mueller, Christian P. (BIOLOGICAL PSYCHIATRY, 2021)
CRIS-Team WoS Importer:2021-05-21

Neutral Sphingomyelinase is an Affective Valence-Dependent Regulator of Learning and Memory - Kalinichenko, Liubov; Abdel-Hafiz, Laila; Wang, An Li; Mühle, Christiane; Rösel, Nadine; Schumacher, Fabian; Kleuser, Burkhard; Smaga, Irena; Frankowska, Malgorzata; Filip, Malgorzata; Schaller, Gerd; Richter-Schmidinger, Tanja; et al. (Cerebral Cortex, 2021)
Sphingolipids and enzymes of the sphingolipid rheostat determine synaptic appearance and signaling in the brain, but sphingolipid contribution to normal behavioral plasticity is little understood. Here we asked how the sphingolipid rheostat contributes to learning and memory of various dimensions. We investigated the role of these lipids in the mechanisms of two different types of memory, such as appetitively and aversively motivated memory, which are considered to be mediated by different neural mechanisms. We found an association between superior performance in short- A nd long-term appetitively motivated learning and regionally enhanced neutral sphingomyelinase (NSM) activity. An opposite interaction was observed in an aversively motivated task. A valence-dissociating role of NSM in learning was confirmed in mice with genetically reduced NSM activity. This role may be mediated by the NSM control of N-methyl-d-aspartate receptor subunit expression. In a translational approach, we confirmed a positive association of serum NSM activity with long-term appetitively motivated memory in nonhuman primates and in healthy humans. Altogether, these data suggest a new sphingolipid mechanism of de-novo learning and memory, which is based on NSM activity.
CRIS-Team Scopus Importer:2021-02-12
Keywords: ceramide; learning; memory; neutral sphingomyelinase; sphingomyelin

New molecular targets for antidepressant drugs - Kornhuber, Johannes; Gulbins, Erich (Pharmaceuticals, 2021)
Major depressive disorder (MDD) is a common and severe mental disorder that is usually recurrent and has a high risk of suicide. This disorder manifests not only with psychological symptoms but also multiple changes throughout the body, including increased risks of obesity, diabetes, and cardiovascular disease. Peripheral markers of oxidative stress and inflammation are elevated. MDD is therefore best described as a multisystem whole-body disease. Pharmacological treatment with antidepressants usually requires several weeks before the desired effects manifest. Previous theories of depression, such as the monoamine or neurogenesis hypotheses, do not explain these characteristics well. In recent years, new mechanisms of action have been discovered for long-standing antidepressants that also shed new light on depression, including the sphingolipid system and the receptor for brain-derived neurotrophic factor (BDNF).
CRIS-Team Scopus Importer:2021-10-01
Keywords: Acid sphingomyelinase; Antidepressant drug; Autophagy; Brain-derived neurotrophic factor (BDNF); Ceramide; FIASMA; Hippocampus; Lysosome; Neurogenesis; Sphingomyelin

New ways to cope with depression—study protocol for a randomized controlled mixed methods trial of bouldering psychotherapy (BPT) and mental model therapy (MMT) - Kind, Leona; Luttenberger, Katharina; Leßmann, Vivien; Dorscht, Lisa; Mühle, Christiane; Müller, Christian P.; Siegmann, Eva-Maria; Schneider, Sophia; Kornhuber, Johannes (Trials, 2023)
Background: Due to the growing gap between the demand and supply of therapeutic services for people suffering from depression, with this study, we are investigating the effectiveness and factors of influence of new approaches in group treatments for depression. Two previous studies have already identified bouldering psychotherapy (BPT) as an effective option. It combines psychotherapeutic interventions with action- and body-oriented bouldering exercises. Mental model therapy (MMT) is a new cognitive-behavioral approach for treating depression. It focuses on identifying cognitive distortions, biases in decision making, and false assumptions and aims to correct and replace them with useful mental models. We aim to investigate the effectiveness of the interventions compared with a control group (CG) and to assess the factors of influence in a mixed methods approach. Methods: The study is being conducted as a randomized controlled intervention trial. Adult participants with unipolar depression are being randomized into three groups (BPT, MMT, or CG), and the first two groups are undergoing a 10-week treatment phase. CG follows their individual standard treatment as usual. A priori power analysis revealed that about 120 people should be included to capture a moderate effect. The primary outcome of the study is depression rated with the Montgomery and Asberg Depression Rating Scale (MADRS) before (t0), directly after (t1), and 12 months after the intervention phase (t2). Data are being collected via questionnaires, computer-assisted video interviews, and physical examinations. The primary hypotheses will be statistically analyzed by mixed model ANOVAs to compare the three groups over time. For secondary outcomes, further multivariate methods (e.g., mixed model ANOVAs and regression analyses) will be conducted. Qualitative data will be evaluated on the basis of the qualitative thematic analysis. Discussion: This study is investigating psychological and physical effects of BPT and MMT and its factors of influence on outpatients suffering from depression compared with a CG in a highly naturalistic design. The study could therefore provide insight into the modes of action of group therapy for depression and help to establish new short-term group treatments. Methodological limitations of the study might be the clinical heterogeneity of the sample and confounding effects due to simultaneous individual psychotherapy. Trial registration: ISRCTN, ISRCTN12347878. Registered 28 March 2022, https://www.isrctn.com/ISRCTN12347878 .
CRIS-Team Scopus Importer:2023-09-29
Keywords: Biomarkers; Bouldering; Depression; Exercise; Factors of influence; Mental models; Osteocalcin; Psychotherapy; Rock climbing; Sports

No association between the ALDH2 promoter polymorphism rs886205, alcohol dependence, and risky alcohol consumption in a German population - Nassab, Mani Haschemi; Rhein, Mathias; Heese, Peter; Glahn, Alexander; Frieling, Helge; Linnebank, Michael; Bleich, Stefan; Kornhuber, Johannes; Heberlein, Annemarie; Grallert, Harald; Peters, Annette; Rawal, Rajesh; et al. (Psychiatric Genetics, 2015)
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No association of the variant rs11887120 in DNMT3A with cognitive decline in individuals with mild cognitive impairment - Bey, Katharina; Wolfsgruber, Steffen; Karaca, Ilker; Wagner, Holger; Lardenoije, Roy; Becker, Julian; Milz, Esther; Kornhuber, Johannes; Peters, Oliver; Froelich, Lutz; Huell, Michael; Ruether, Eckart; et al. (Epigenomics, 2016)
Alterations in DNA methylation have been associated with cognitive decline and Alzheimer's disease. A recent study of mild cognitive impairment (MCI) reported a significant association between annual decline in cognitive function and the rs11887120 SNP located in DNMT3A, a gene implicated in DNA methylation. Here, we aimed to replicate this finding in two independent MCI cohorts (n = 1024); however, no significant association was observed in either cohort or the pooled dataset. In stratified analyses for conversion to Alzheimer's disease status, no association between rs11887120 and cognitive decline was observed in either converters or nonconverters. In conclusion, our analyses provide no support for the hypothesis that genetic variants in DNMT3A are implicated in cognitive performance decline in individuals with MCI.
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No juvenile arterial hypertension in sheep multiples despite reduced nephron numbers - Muehle, Anja; Mühle, Christiane; Amann, Kerstin Ute; Dötsch, Jörg; Nuesken, Kai-Dietrich; Boltze, Johannes; Schneider, Holm (Pediatric Nephrology, 2010)
Low birth weight is associated with an increased risk of metabolic dysfunction and arterial hypertension in later life. Because of their reduced birth weight twins have been used repeatedly as a natural model to investigate prenatal programming of hypertension. To reveal an early impact of lower nephron endowment on blood pressure, we performed a longitudinal study on lambs from single, twin and triplet pregnancies. The lambs were studied from birth until adulthood, including regular blood analyses, measurements of body weight and blood pressure and post-mortem estimation of glomerular numbers. Relative weight differences between multiples and singletons at birth were -28% for twins and -44% for triplets, respectively. Some lambs showed rapid catch-up growth. Total nephron number of twins and triplets was reduced by 21 and 37% with respect to that of singletons (p∈<∈0.01). However, multiples did not show increased blood pressure within the time frame of this study. No gender-specific effect was observed. Plasma concentrations of creatinine, urea, electrolytes or osmolality also did not differ. Our data indicate that the previously reported postnatal blood pressure differences between sheep multiples and singletons are a time-limited phenomenon. During infancy and adolescence, a reduced nephron number in sheep multiples is neither associated with increased blood pressure nor reflected by plasma parameters. © 2010 IPNA.
CRIS-Team Scopus Importer:2020-07-01
Keywords: Blood pressure; Nephron number; Prenatal programming

Non-invasive separation of alcoholic and non-alcoholic liver disease with predictive modeling - Sowa, Jan-Peter; Atmaca, Ozgur; Kahraman, Alisan; Schlattjan, Martin; Lindner, Marion; Sydor, Svenja; Scherbaum, Norbert; Lackner, Karoline; Gerken, Guido; Heider, Dominik; Arteel, Gavin E.; Erim, Yesim; et al. (PLoS ONE, 2014)
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Non-pharmacological factors that determine drug use and addiction - Ahmed, Serge H.; Badiani, Aldo; Miczek, Klaus A.; Müller, Christian P. (Neuroscience and Biobehavioral Reviews, 2020)
Based on their pharmacological properties, psychoactive drugs are supposed to take control of the natural reward system to finally drive compulsory drug seeking and consumption. However, psychoactive drugs are not used in an arbitrary way as pure pharmacological reinforcement would suggest, but rather in a highly specific manner depending on non-pharmacological factors. While pharmacological effects of psychoactive drugs are well studied, neurobiological mechanisms of non-pharmacological factors are less well understood. Here we review the emerging neurobiological mechanisms beyond pharmacological reinforcement which determine drug effects and use frequency. Important progress was made on the understanding of how the character of an environment and social stress determine drug self-administration. This is expanded by new evidence on how behavioral alternatives and opportunities for drug instrumentalization generate different patterns of drug choice. Emerging evidence suggests that the neurobiology of non-pharmacological factors strongly determines pharmacological and behavioral drug action and may, thus, give rise for an expanded system's approach of psychoactive drug use and addiction.
CRIS-Team Scopus Importer:2020-03-13
Keywords: Drug abuse; Drug addiction; Drug instrumentalization; Environment; Social stress

Non-pharmacological, psychosocial MAKS-s intervention for people with severe dementia in nursing homes: results of a cluster-randomised trial - Kratzer, André; Diehl, Kristina; Gefeller, Olaf; Meyer, Sebastian; Grässel, Elmar (BMC Geriatrics, 2022)
Background: Severe dementia is one of the most challenging conditions when caring for people in nursing homes. A manualised non-pharmacological, psychosocial group intervention especially adapted to the needs of people with severe dementia (PWSDs) is currently still lacking. To close this gap, we adapted the evidence-based multicomponent non-pharmacological MAKS intervention (Motor stimulation, ADL stimulation, Cognitive [german: Kognitive] stimulation, and Social functioning in a group setting) to the special needs of PWSDs called the MAKS-s intervention, where the s stands for severe dementia. Methods: In a prospective, multicentre, cluster-randomised trial with a waitlist control group design, 26 nursing homes comprising 152 PWSDs were randomly assigned to either the MAKS-s intervention group (IG) or control group (CG) – 121 PWSDs were still alive after the 6-month intervention period (t6) and included in the intention-to-treat (ITT) sample. The two primary outcomes, behavioural and psychological symptoms (BPSDs, measured with NPI-NH) and quality of life (QoL, measured with QUALIDEM), and the secondary outcome, activities of daily living (ADLs, measured with ADCS-ADL-sev), were assessed at baseline (t0) and at t6. Mixed ANOVAs were computed to investigate possible effects of the MAKS-s intervention on the outcomes. Results: In the ITT sample, BPSDs and QoL did not change significantly over time, and group assignment did not affect them, although the IG participants had significantly better overall QoL than the CG participants. ADLs decreased significantly over time, but group assignment did not affect them. Analyses in the per protocol (PP) sample showed comparable results, with the exception that the IG participants showed a significantly greater increase in BPSDs than the CG participants did. Discussion: Under the situational conditions of the Covid-19 pandemic, no beneficial effects of the MAKS-s intervention on BPSDs, QoL, or ADLs were observed. This finding also means that under ‘normal circumstances’ (i.e., if there had been no pandemic), we could not make any statements about the effect or non-effect of MAKS-s. In order to be able to address the hypotheses formulated here, the study will have to be repeated incorporating helpful experiences of the present study. Trial registration: https://doi.org/10.1186/ISRCTN15722923 (Registered prospectively, 07. August 2019).
Created from Fastlane, Scopus look-up
Keywords: Behavioural and psychological symptoms of dementia; Nursing home; Psychosocial intervention; Quality of life; RCT; Severe dementia

Non-Pharmacological Treatment in People With Cognitive Impairment - Straubmeier, Melanie; Behrndt, Elisa-Marie; Seidl, Hildegard; Özbe, Dominik; Luttenberger, Katharina; Grässel, Elmar (Deutsches Ärzteblatt international, 2017)
BACKGROUND: A number of non-pharmacological methods are available to help elderly people with cognitive impairment. Unstructured and non-evidencebased interventions are commonly used. The multicomponent therapy MAKS (a German acronym for Motor, Activities of daily living, Cognitive, Social) has already been evaluated in nursing homes; in this study, we investigated its use in day care centers (DCCs). METHODS: A cluster-randomized, controlled, single-blinded trial involving a 6-month intervention phase was performed. 362 cognitively impaired persons in 32 DCCs took part in the trial. Multiple regression analyses were used to determine whether MAKS therapy led to any statistically significant and clinically relevant improvement over time (compared to membership in the control group) in these persons' cognitive abilities and activities of daily living (ADL) abilities, as assessed, respectively, with the Mini-Mental State Examination (MMSE) and the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM). A primary per-protocol analysis was supplemented by an intention-to-treat analysis. Two secondary outcomes (social behavior and neuropsychiatric symptoms) were analyzed exploratively as well. Study registration: ISRCTN16412551. RESULTS: In the primary per-protocol analysis at 6 months, the intervention group had significantly better MMSE and ETAM scores than the control group (Cohen's d, 0.26 and 0.21, respectively; p = 0.012 for both). The same was found in the ITT analysis at 6 months (Cohen's d = 0.21, p = 0.033; and Cohen's d = 0.20, p = 0.019, respectively). Neuropsychiatric symptoms, one of the secondary outcomes, also evolved more favorably in the intervention group (Cohen's d = 0.23, p = 0.055). CONCLUSION: MAKS therapy is effective for persons with cognitive impairment ranging from mild cognitive impairment (MCI) to moderate dementia who live at home and regularly visit a day care center. The fact that 32 day care facilities from all over Germany participated in this study gives its findings high external validity.
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Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization - Lewczuk, Piotr; Lelental, Natalia; Lachmann, Ingolf; Holzer, Max; Flach, Katharina; Brandner, Sebastian; Engelborghs, Sebastiaan; Teunissen, Charlotte E.; Zetterberg, Henrik; Luis Molinuevo, Jose; Mroczko, Barbara; Blennow, Kaj; et al. (Journal of Alzheimer's Disease, 2017)
BACKGROUND: Virtually nothing is known about a potential diagnostic role of non-phospho-epitopes of Tau (Non-P-Tau) in cerebrospinal fluid (CSF). OBJECTIVE: To establish and analytically and clinically characterize the first assay capable to measure concentrations of Non-P-Tau in human CSF. METHODS: An antibody (1G2) was developed that selectively binds to the Tau molecule non-phosphorylated at the positions T175 and T181, and was used in establishing a sandwich ELISA capable to measure Non-P-Tau in human CSF, following analytical and clinical validation of the method. RESULTS: The 1G2 antibody shows decreasing reactivity to tau peptides containing phosphorylation mainly at positions T175 and T181. Detection limit of the assay is 25 pg/ml; the coefficients of variation (CVs) of the optical densities of the repeated standard curves were between 3.6-15.9%. Median intra-assay imprecision of double measurements was 4.8%; inter-assay imprecision was in the range of 11.2% - 15.3%. Non-P-Tau concentrations are stable in the CSF samples sent to distinct laboratories under ambient temperature; inter-laboratory variation was approximately 30%. The Non-P-Tau CSF concentrations were highly significantly increased in patients with Alzheimer's disease in stage of mild cognitive impairment or dementia (AD/MCI, n = 58, 109.2±32.0 pg/mL) compared to the non-demented Controls (n = 42, 62.1±9.3 pg/mL, p < 0.001). At the cut-off of 78.3 pg/mL, the sensitivity and the specificity were 94.8% and 97.6%, respectively. CONCLUSION: For the first time, an assay is reported to reliably measure concentrations of non-phosphorylated Tau in human CSF.
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"Not suicidal": How valid is this clinical judgment? - Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2016)
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Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs - Hassan, Zurina; Bosch, Oliver G.; Singh, Darshan; Narayanan, Suresh; Kasinather, B. Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B.; Müller, Christian P. (Frontiers in Psychiatry, 2017)
A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug's properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ("Kratom"), synthetic cannabinoids (e.g., "Spice"), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.
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N-truncation and pyroglutaminylation enhances the opsonizing capacity of A?-peptides and facilitates phagocytosis by macrophages and microglia - Condic, Mateja; Oberstein, Timo; Herrmann, Martin; Reimann, Mareike Carola; Kornhuber, Johannes; Maier, Jan-Niklas; Spitzer, Philipp (Brain Behavior and Immunity, 2014)
Abnormal accumulations of amyloid-? (A?)-peptides are one of the pathological hallmarks of Alzheimer's disease (AD). The precursor of the A?-peptides, the amyloid precursor protein (APP), is also found in peripheral blood cells, but its function in these cells remains elusive. We previously observed that mononuclear phagocytes release A?-peptides during activation and phagocytosis, suggesting a physiologic role in inflammatory processes. Here, we show that supplementing the media with soluble N-terminally truncated A?(2-40) and A?(2-42) as well as A?(1-42) induced the phagocytosis of polystyrene particles (PSPs) by primary human monocytes. If the PSPs were pre-incubated with A?-peptides, phagocytosis was induced by all tested A?-peptide species. N-terminally truncated A?(x-42) induced the phagocytosis of PSPs significantly more effectively than did A?(x-40). Similarly, the phagocytosis of Escherichia coli by GM-CSF- and M-CSF-elicited macrophages as well as microglia was particularly facilitated by pre-incubation with N-terminally truncated A?(x-42). The proinflammatory polarization of monocytes was indicated by the reduced MSRI expression and IL-10 secretion after phagocytosis of PSPs coated with A?(1-42), A?(2-42) and A?(3p-42). Polarization of the macrophages by GM-CSF reduced the phagocytic activity, but it did not affect the capabilities of A?-peptides to opsonize prey. Taken together, A?-peptides support phagocytosis as soluble factors and act as opsonins. Differential effects among the A?-peptide variants point to distinct mechanisms of interaction among monocytes/macrophages, prey and A?-peptides. A proinflammatory polarization induced by the phagocytosis of A?-peptide coated particles may provide a model for the chronic inflammatory reaction and sustained plaque deposition in AD.
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Nutrition claims influence expectations about food attributes, attenuate activity in reward-associated brain regions during tasting, but do not impact pleasantness - Rramani, Qendresa; Barakat, Youssef; Jacob, George; Ohla, Kathrin; Lim, Shirley Xue Li; Schicker, Doris; Freiherr, Jessica; Saruco, Elodie; Pleger, Burkhard; Weber, Bernd; Schultz, Johannes (Brain and Behavior, 2022)
IntroductionNutrition claims are one of the most common tools used to improve food decisions. Previous research has shown that nutrition claims impact expectations; however, their effects on perceived pleasantness, valuation, and their neural correlates are not well understood. These claims may have both intended and unintended effects on food perception and valuation, which may compromise their effect on food decisions. MethodsWe investigated the effects of nutrition claims on expectations, perceptions, and valuation of milk-mix drinks in a behavioral (n = 110) and an fMRI (n = 39) study. In the behavioral study, we assessed the effects of a "fat-reduced" and a "protein-rich" nutrition claim on expected and perceived food attributes of otherwise equal food products. In the fMRI study, we investigated the effect of a "protein-rich" claim on taste pleasantness perception and valuation, and on their neural correlates during tasting and swallowing. ResultsWe found that both nutrition claims increased expected and perceived healthiness and decreased expected but not perceived taste pleasantness. The "protein-rich" claim increased expected but not perceived satiating quality ratings, while the "fat-reduced" claim decreased both expected and perceived satiating quality ratings. In the absence vs. presence of the "protein-rich" claim, we observed an increased activity in a cluster extending to the left nucleus accumbens during tasting and an increased functional connectivity between this cluster and a cluster in right middle frontal gyrus during swallowing. ConclusionAltogether, we found that nutrition claims impacted expectations and attenuated reward-related responses during tasting but did not negatively affect perceived pleasantness. Our findings support highlighting the presence of nutrients with positive associations and exposure to foods with nutrition claims to increase their acceptance. Our study offers insights that may be valuable in designing and optimizing the use of nutrition claims.
CRIS-Team WoS Importer:2022-12-30

Nutzung von Anschlussmaßnahmen nach stationärem Alkoholentzug: Annahmen zum Stand der Vernetzung im deutschen Suchthilfesystem - Reichl, Daniela; Enewoldsen, Niklas; Tegethoff, Paulina; Gendlina, Taisia; Saur, Sebastian; Lang, Catharina; Fuhrmann, Lukas; Weisel, Kiona; Berking, Matthias; Zink, Mathias; Ahnert, Andreas; Falkai, Peter; et al. (Sucht, 2023)
Aims: The present study addresses potential problems with treatment transition by investigating the use of aftercare treatments by inpatients after alcohol withdrawal treatment without immediate transition to rehabilitation. Methods: We analyzed the control group of the SmartAssistEntz project. Therefor, 181 individuals were interviewed three and six weeks, as well as three and six months after their withdrawal treatment, assessing information regarding the use and evaluation of different aftercare treatments. Results: Over the course of the study, more than half of the participants reported using at least one aftercare treatment. Mostly and most continuously used were drug counseling offers (20-35 % of the participants). Rehabilitation treatments were reported by 8-14 % of the participants six weeks after withdrawal treatment, and by 27-33 % six months thereafter. The treatments were mostly considered to be "helpful", whereby self-help groups performed worst. The reason for the lack of aftercare was mostly waiting time (12-22 % of the cases). The use of rehabilitation treatment during the first three months after withdrawal treatment was associated with a reduced risk of relapse. Conclusions: Particularly drug counseling offers seem to be a low-threshold and subjectively helpful measure following inpatient withdrawal treatment. At the same time, regarding abstinence, the visit of rehabilitation treatments seems to be decisive. Thus, their use should be promoted more intensely.
CRIS-Team Scopus Importer:2023-12-01
Keywords: aftercare treatment; alcohol; health care; withdrawal treatment

Olfactory-trigeminal Masking Effects - Ruda, Iryna; Muschenich, Franziska Sonja; Freiherr, Jessica (CHEMICAL SENSES, 2021)
CRIS-Team WoS Importer:2021-12-24

One year of general practice during the COVID-19 pandemic - presentation and evaluation of digital medical education - van der Keylen, Piet; Zeschick, Nikoletta; Langer, Amelie; Kühlein, Thomas; Roos, Marco (GMS Journal for Medical Education, 2022)
Background and teaching situation: The SARS-CoV-2 pandemic had a substantial didactic impact on medical teaching. In Erlangen, the lecture "General Practice" was offered asynchronously and digitally in an inverted-classroom concept. Contents were available via a learning platform. The lecture was presented using annotated videos, consolidation materials and control questions. A forum encouraged for discussions and feedback and collected in-depth aspects for a case-based video consultation. The aim of this work is to evaluate and critically examine the digital teaching concept during the SARS-CoV-2 pandemic.
CRIS-Team WoS Importer:2022-09-09

Oniomania: A Psychiatry-Historical Perspective Oniomanie: Eine psychiatrie-historische Perspektive - Demling, Joachim; Müller, Astrid (Sucht, 2023)
Objective: Psychiatry-historical perspective on the conceptualization and classification of "oniomania". Method: Focused narrative review. Results: The term "oniomania"was probably coined in the 19th century by the French psychiatrist Magnan, and later associated primarily with Kraepelin. Kraepelin and Bleuler described "oniomania"in short paragraphs of their psychiatric textbooks. The nosological classification occurred initially within the framework of the "degenerative theory"of the 19th century; at the beginning of the 20th century, Kraepelin referred to it as "pathological drives,"Bleuler, following Kraepelin, as "impulsive mania,"and later as "psychogenic disorders"and as "pathological reactions of thymopsychic nature". The term "oniomania"appears very rarely in the current literature. Instead, terms such as "shopping addiction,""pathological buying,"or "compulsive buying"are preferred. In the ICD-11, "compulsive buying-shopping disorder"is listed as an example in the category "other specified impulse control disorders". Neuropsychological findings, however, support its classification as a disorder due to addictive behavior. Conclusions: The label "oniomania"emerged more than 100 years ago and can be seen as a precursor to the ICD-11 term "compulsive buying-shopping disorder."Currently, the disorder is viewed as an impulse control disorder or behavioral addiction.
CRIS-Team Scopus Importer:2023-09-01
Keywords: addictive buying; compulsive buying; compulsive buying-shopping disorder; oniomania; pathological buying

Online shopping in treatment-seeking patients with buying-shopping disorder - Müller, Astrid; Steins-Loeber, Sabine; Trotzke, Patrick; Vogel, Birte; Georgiadou, Ekaterini; de Zwaan, Martina (Comprehensive Psychiatry, 2019)
Background and aims: With e-commerce becoming an important shopping activity, it has been argued that traditional buying-shopping disorder (BSD) migrates to the online retail market resulting in BSD predominantly online. The aims of the current study were to investigate how many patients with BSD report symptoms of online BSD, and to determine whether symptoms of probable online BSD are related to sociodemographic variables, anxiety, depression, and a higher severity of general BSD. Method: A post hoc analysis of pooled data collected within previous studies (n = 122 treatment-seeking patients with BSD; age Mdn = 42.50, range 20–68 years; 76% women) was conducted. Assessment included the short version of the Internet Addiction Test modified for online shopping sites (s-IATshop), the Pathological Buying Screener (PBS) as an instrument assessing BSD in general, regardless of the buying or shopping environment, and measures for anxiety and depression. Results: 33.6% of the sample met the s-IAT threshold for probable online BSD. Higher s-IAT scores were related to lower age and to a higher severity of anxiety, depression and general BSD. A hierarchical regression analysis with general BSD (PBS score) as dependent variable and partnership status, symptoms of anxiety, depression and online BSD (s-IAT-shop) as predictors indicated a significant positive association of probable online BSD with the severity of general BSD above and beyond anxiety and depression. Conclusion: The findings may encourage future studies addressing phenomenological characteristics, underlying features, associated comorbidity, and clinical relevance of online BSD.
CRIS-Team Scopus Importer:2019-09-20
Keywords: Buying addiction; Compulsive buying-shopping disorder; Internet-use disorder; Online buying-shopping disorder; Pathological buying

On the Automatic Classification of Reading Disorders - Maier, Andreas; Schafflhuber, Caroline; Bocklet, Tobias; Hönig, Florian Thomas; Kratz, Oliver; Horndasch, Stefanie; Nöth, Elmar; Moll, Gunther (Pattern Recognition in Information Systems, 2009)

Opioid receptors mediate the acquisition, but not the expression of mitragynine-induced conditioned place preference in rats - Yusoff, Nurul H. M.; Mansor, Sharif M.; Müller, Christian P.; Hassan, Zurina (Behavioural Brain Research, 2017)
Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats. In the first experiment we tested the effects of the opiate receptor antagonist naloxone (0.1, 0.3 and 1.0mg/kg) on the acquisition of mitragynine (10mg/kg)-induced CPP. In the second experiment, we tested the involvement of opiate receptors in the expression of mitragynine-induced CPP in rats. We found that naloxone suppresses the acquisition of mitragynine-induced CPP. This effect was already evident at a dose of naloxone (0.1mg/kg) which, by itself, had no conditioned place aversion (CPA) effect. Higher doses of naloxone induced a CPA and blocked mitragynine-induced CPP. In contrast, naloxone had no effect on the expression of mitragynine-induced CPP. These findings suggest that the acquisition, but not the expression of the reinforcing effects of mitragynine is mediated by opiate receptors.
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OPRM1 A118G and serum β-endorphin interact with sex and digit ratio (2D:4D) to influence risk and course of alcohol dependence - Gegenhuber, Bruno; Weinland, Christian; Kornhuber, Johannes; Mühle, Christiane; Lenz, Bernd (European Neuropsychopharmacology, 2018)
Activation of mesolimbic mu-opioid receptors by their endogenous ligand, β-endorphin, can mediate the rewarding effects of alcohol. However, there is conflicting evidence on the relationship between the mu-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) and alcohol dependence risk. Preclinical evidence suggests that sex and sex hormone-dependent prenatal brain organization may interact with the opioid system to influence alcohol drinking behavior. We genotyped 200 alcohol-dependent patients and 240 healthy individuals for the OPRM1 A118G SNP and measured serum β-endorphin level at recruitment and after acute withdrawal. We then determined the association between these factors and alcohol dependence risk and 24-month outcome in the context of both sex and second-to-fourth digit lengths ratio (2D:4D) - a biomarker of prenatal sex hormone levels. The OPRM1 A118G AA genotype associated with elevated risk of alcohol-related hospital readmission, more readmissions, and fewer days until first readmission in male patients only. After normalizing patient 2D:4D against control 2D:4D, we found that normalized 2D:4D ratios were lower in male 118G patients than male AA patients, suggesting prenatal androgens interact with OPRM1 to influence alcohol dependence risk. In addition, β-endorphin levels after acute withdrawal correlated negatively with withdrawal severity in females but not in males, which may indicate β-endorphin protects against withdrawal-induced stress in a sex-specific manner.
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Optimization of electronically monitored non-adherence in highly adherent renal transplant recipients by reducing the dosing frequency – a prospective single-center observational study - Lieb, Marietta; Schiffer, Mario; Erim, Yesim (Patient Preference and Adherence, 2020)
Background: Non-adherence (NA) after renal transplantation poses a major risk for allo-graft rejection, graft loss, and patient mortality. Yet, there is still ambiguity about its etiology and its possible relationships with patient-related factors. In order to prevent poor outcomes after transplantation, it is crucial to gain a more refined understanding of potential determi-nants, to identify patients at risk, and to intervene accordingly. The objective of this study was to assess potential risk factors of NA by prospectively applying electronic monitoring. Materials and Methods: This was a single-center prospective observational study. Prior to study initiation, sociodemographic, biomedical, and psychosocial variables (depression, health-related quality of life, self-efficacy, social support, attachment, experiences and attitudes towards immunosuppressive medication, emotional responses after organ transplantation, satisfaction with information about immunosuppressive medication, and perceptions and beliefs about medications) were assessed. Thereafter, immunosuppressive adherence behavior was measured prospectively via electronic monitoring (EM, VAICA©) during a 3-month period to receive the percentage frequency of Taking and Timing Adherence (±2h, ±30min) for each patient. Focus of this study was the phase of medication implementation. Results: A total of 78 patients participated in our study (mean age 55.28, 56% male). We found rates of 99.39% for Taking Adherence, 98.34% for Timing Adherence ±2h, and 93.34% for Timing Adherence ±30min, respectively. Multiple regression analyses revealed that the type of medication could significantly predict Taking Adherence. Patients receiving Advagraf© (once daily) depicted better Taking Adherence than patients receiving Prograf© (twice daily) (p=0.04). No associations were found for Timing Adherence (±2h, ±30min). Sociodemographic, biomedical, or psychosocial variables were not found to be associated with adherence behavior. Discussion: In highly adherent populations, only a few factors can be altered to improve adherence. Changing the immunosuppressive regimen from twice-daily to once-daily could be an option for optimizing adherence. However, risk factors for NA could be different in a less adherent population.
CRIS-Team Scopus Importer:2020-08-14
Keywords: Adherence; Electronic monitoring; Immunosuppressive medication; Patient-related factors; Psychosocial variables

Out of the woods: psychophysiological investigations on wood odors to estimate their suitability as ambient scents - Schreiner, Linda; Karacan, Brid; Blankenagel, Sonja; Packhaeuser, Kai; Freiherr, Jessica; Loos, Helene (Wood Science and Technology, 2020)
Wood has been an important raw material for centuries, and humans encounter it in the form of furniture and building materials or in products of daily use. The odors emanating from such wood-based materials can add another facet to their functionality by influencing human well-being and mood. Moreover, wood odors can be used in odor-enhanced environments to foster relaxation and stress recovery. The current study was conducted to assess the subjective evaluation of, and physiological responses to, wood odors and individual wood odor constituents. The subjects smelled the odors of pine needles oil, cedar wood oil, α-pinene, and thymoquinone and evaluated the odor percept and their subjective feelings. Heart rate, finger temperature, and skin conductance were monitored throughout the experiment. The results showed that wood odors were distinct regarding their pleasantness, familiarity, and intensity. All odors enhanced the subjective feelings of happiness and content. Though no odor-specific physiological effects became evident, certain physiological measures correlated with self-reports of happy and relaxed feelings and the intensity ratings of the odors. The present study provides a basis for further studies on the use of wood odors as ambient scents and helps understanding the influence of natural odors on humans.
CRIS-Team Scopus Importer:2020-09-11

Oxytocin blood concentrations in alcohol use disorder: A cross-sectional, longitudinal, and sex-separated study - Lenz, Bernd; Weinland, Christian; Bach, Patrick; Kiefer, Falk; Grinevich, Valery; Zoicas, Iulia; Kornhuber, Johannes; Mühle, Christiane (European Neuropsychopharmacology, 2021)
Alcohol use disorder (AUD) is a severe illness, for which we lack sufficient mechanistic understanding. Preliminary evidence associates AUD with the oxytocin (OXT) system. Here we investigated alterations in endogenous OXT blood concentrations in patients with AUD and their association with alcohol drinking and prospective course. In sex-separated analyses, OXT serum concentrations of 200 in-patients with AUD (56.5% male; baseline, 24–72 h of abstinence) were compared with those of 240 age-matched healthy controls (55.4% male), investigated longitudinally (follow-up, 5 days later), and tested for associations with alcohol drinking behavior and prospective 24-month alcohol-related hospital readmissions. At baseline, the patients showed increased OXT concentrations relative to controls (men, 156%, P < 0.001; women, 124%, P = 0.002). The elevations normalized at follow-up. In male patients, baseline OXT concentrations correlated positively with alcohol concentration at admission, the amount of alcohol consumption per drinking year, and the number of previous withdrawal treatments (Rho > 0.195, P < 0.044). In beverage type-specific analysis, baseline OXT concentrations correlated with liquor consumption positively in male and negatively in female patients (|Rho| > 0.277, P < 0.017). Higher baseline OXT concentrations predicted more readmissions and fewer days to the first readmission (|Rho| > 0.185, P < 0.050) in male patients. This study provides novel and sex-separated insights into the role of the OXT system in AUD. We identified a mechanism that might underlie the sex-separated choice of beverage type and established that increased OXT concentrations during early abstinence predict a worse outcome in male patients with AUD.
CRIS-Team Scopus Importer:2021-06-11
Keywords: Alcohol dependence; Alcohol use disorder; Alcoholic beverages; Alcoholism; Ethanol; Oxytocin; Patient readmission; Prospective studies

Oxytocin receptor DNA methylation in postpartum depression - Kimmel, Mary; Clive, Makena; Gispen, Fiona; Guintivano, Jerry; Brown, Tori; Cox, Olivia; Beckmann, Matthias; Kornhuber, Johannes; Fasching, Peter; Osborne, Lauren M.; Binder, Elisabeth; Payne, Jennifer L.; et al. (Psychoneuroendocrinology, 2016)
The oxytocin receptor (OXTR) is a key regulator of stress and anxiety and may be regulated by both psychosocial risk factors and gonadal hormones, making it an attractive candidate for study in postpartum depression (PPD). The objective of this study was to investigate both serum hormone and PPD specific DNA methylation variation in the OXTR. Illumina HM450 microarray data generated in a prospective PPD cohort identified significant associations (P=0.014) with PPD in an intronic region in the OXTR located 4bp proximal to an estrogen receptor (ER) binding region. Pyrosequencing confirmed moderate evidence for an interaction of CpGs in the region with childhood abuse status to mediate PPD. These CpGs located on chr3 at positions 8810078 and 8810069 exhibited significant associations with postpartum depression scores from an independent cohort of 240 women with no prior psychiatric history. Hormone analysis suggested a PPD specific negative correlation of DNA methylation in the region with serum estradiol levels. Estradiol levels and OXTR DNA methylation exhibited a significant interaction to associate with the ratio of allopregnanolone to progesterone. Cumulatively, the data corroborate our previous hypotheses of a PPD specific increased sensitivity of epigenetic reprogramming at estrogen target genes and suggests that OXTR epigenetic variation may be an important mediator of mood relevant neuroactive steroid production.
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P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy - Neyazi, Alexandra; Theilmann, Wiebke; Brandt, Claudia; Rantamaki, Tomi; Matsui, Nobuaki; Rhein, Mathias; Kornhuber, Johannes; Bajbouj, Malek; Sperling, Wolfgang; Bleich, Stefan; Frieling, Helge; Loescher, Wolfgang (Translational Psychiatry, 2018)
Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response. Our hypothesis was that the promoter methylation of p11, a multifunctional protein involved in both depressive-like states and antidepressant treatment responses, is differently regulated in ECT responders vs. nonresponders and thus be a putative biomarker of ECT response. The chronic mild stress model of MDD was adapted with the aim to obtain rats that are resistant to conventional antidepressant drugs (citalopram). Subsequently, electroconvulsive stimulation (ECS) was used to select responders and nonresponders, and compare p11 expression and promoter methylation. In the rat experiments we found that the gene promoter methylation and expression of p11 significantly correlate with the antidepressant effect of ECS. Next, we investigated the predictive properties of p11 promoter methylation in two clinical cohorts of patients with pharmacoresistant MDD. In a proof-of-concept clinical trial in 11 patients with refractory MDD, higher p11 promoter methylation was found in responders to ECT. This finding was replicated in an independent sample of 65 patients with pharmacoresistant MDD. This translational study successfully validated the first biomarker reliably predicting the responsiveness to ECT. Prescreening of this biomarker could help to identify patients eligible for first-line ECT treatment and also help to develop novel antidepressant treatment procedures for depressed patients resistant to all currently approved antidepressant treatments.
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P22-2-jD Mit hydrostatischem Hochdruck generierte Ganzzell- Tumorvakzine erzeugen in Kombination mit Strahlentherapie ein immunogenes Tumor-Mikromilieu - Rückert, Michael; Seitz, Christoph; Deloch, Lisa; Weiss, Eva-Maria; Utz, S; Izydor, Marika; Ebel, Nina; Schlücker, Eberhard; Fietkau, Rainer; Gaipl, Udo; Frey, Benjamin (2019)

Panic and comorbid depression and their associations with stress reactivity, interoceptive awareness and interoceptive accuracy of various bioparameters - Limmer, Jan; Kornhuber, Johannes; Martin, Alexandra (Journal of Affective Disorders, 2015)
While current theories on perception of interoceptive signals suggest impaired interoceptive processing in psychiatric disorders such as panic disorder or depression, heart-rate (HR) interoceptive accuracy (IAc) of panic patients under resting conditions is superior to that of healthy controls. Thus, in this study, we chose to assess further physiological parameters and comorbid depression in order to get information on how these potentially conflicting findings are linked together.We used a quasi-experimental laboratory design which included multi-parametric physiological data collection of 40 panic subjects and 53 matched no-panic controls, as well as experimental induction of stress and relaxation over a time-course.Stress reactivity, interoceptive awareness (IAw; from the Body Perception Questionnaire (BPQ)) and IAc (as correlation between self-estimation and physiological data) were major outcome variables. Self-estimation of bioparametrical change was measured via numeric rating scales.Panic subjects had stronger HR-reaction and more accurate HR-interoception. Concurrently, though, their IAc of skin conductance level, pulse amplitude and breathing amplitude was significantly lower than that of the control group. Interestingly, comorbid depression was found to be associated with increased IAw but attenuated IAc.Demand characteristics and a categorical approach to panic confine the results.The potentially conflicting findings coalesce, as panic was associated with an increase of the ability to perceive the fear-related parameter and a simultaneous decrease of the ability to perceive other parameters. The superordinate integration of afferent signals might be impaired.
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Paradoxical antidepressant effects of alcohol are related to acid sphingomyelinase and its control of sphingolipid homeostasis - Müller, Christiane; Kalinichenko, Liubov; Tiesel, Jens; Witt, Matthias; Stöckl, Thomas; Sprenger, Eva; Fuchser, Jens; Beckmann, Janine; Praetner, Marc; Huber, Sabine; Amato, Davide; Mühle, Christiane; et al. (Acta Neuropathologica, 2016)
Alcohol is a widely consumed drug that can lead to addiction and severe brain damage. However, alcohol is also used as self-medication for psychiatric problems, such as depression, frequently resulting in depression-alcoholism comorbidity. Here, we identify the first molecular mechanism for alcohol use with the goal to self-medicate and ameliorate the behavioral symptoms of a genetically induced innate depression. An induced over-expression of acid sphingomyelinase (ASM), as was observed in depressed patients, enhanced the consumption of alcohol in a mouse model of depression. ASM hyperactivity facilitates the establishment of the conditioned behavioral effects of alcohol, and thus drug memories. Opposite effects on drinking and alcohol reward learning were observed in animals with reduced ASM function. Importantly, free-choice alcohol drinking-but not forced alcohol exposure-reduces depression-like behavior selectively in depressed animals through the normalization of brain ASM activity. No such effects were observed in normal mice. ASM hyperactivity caused sphingolipid and subsequent monoamine transmitter hypo-activity in the brain. Free-choice alcohol drinking restores nucleus accumbens sphingolipid- and monoamine homeostasis selectively in depressed mice. A gene expression analysis suggested strong control of ASM on the expression of genes related to the regulation of pH, ion transmembrane transport, behavioral fear response, neuroprotection and neuropeptide signaling pathways. These findings suggest that the paradoxical antidepressant effects of alcohol in depressed organisms are mediated by ASM and its control of sphingolipid homeostasis. Both emerge as a new treatment target specifically for depression-induced alcoholism.
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Parenchymatous hematoma in patients with atraumatic subarachnoid hemorrhage: Characteristics, treatment, and clinical outcomes - Gerner, Stefan; Hülsbrink, Robert; Reichl, Jonathan; Mrochen, Anne; Eyüpoglu, Ilker Yasin; Brandner, Sebastian; Dörfler, Arnd; Engelhorn, Tobias; Kuramatsu, Joji; Schwab, Stefan; Huttner, Hagen (International Journal of Stroke, 2020)
Background: Data regarding the influence of concomitant parenchymatous hematoma (PH) on long-term outcomes in patients with atraumatic subarachnoid hemorrhage (SAH) are scarce. Further, it is not established if these patients benefit from surgical intervention. Aim: The aim of this study was to determine the influence of concomitant PH in SAH patients on functional long-term outcome, and whether these patients may benefit from surgical hematoma evacuation. Methods: Over a 5-year period, all consecutive patients with SAH treated at the Departments of Neurology, Neuroradiology, and Neurosurgery, at the University Hospital Erlangen (Germany) were recorded. In addition to the clinical and imaging characteristics of SAH, we documented the presence, location, and volume of PH as well as treatment parameters. Outcome assessment at 12 months included functional outcome (modified Rankin scale (mRS), favorable = 0–2), health-related quality of life, and long-term complications. For outcome analysis, a propensity score matching (ratio 1:1, caliper 0.1) was performed to compare SAH patients with and without PH. Sub-analyses were performed regarding PH treatment (surgical evacuation vs. conservative). Results: A total of 494 patients with atraumatic SAH were available. Eighty-five (17.2%) had PH on initial imaging. SAH patients with PH had a worse clinical condition on admission and had a greater extent of subarachnoid/intraventricular hemorrhage. Median PH volume was 11.0 ml (5.4–31.8) with largest volumes observed in patients with ruptured middle cerebral artery (MCA)-aneurysm (31.7 ml (16.3–43.2)). After propensity-score matching (PSM), patients with PH had worse functional outcomes at 12 months (modified Rankin scale (mRS) 0–2: PH 31.8% vs. ØPH57.7% p < 0.001), and a lower rate of self-reported health compared to patients without PH (EQ-5D VAS: PH 50(30–70) vs. ØPH 80(65–95); p < 0.001). In PH patients, surgical evacuation was associated with a higher rate of favorable outcome at 12 months compared to those treated conservatively (surgery 14/28 (50.0%) vs. conservative 14/57 (24.6%); adjusted odds-ratio (OR; 95%CI): 1.34 (1.08–1.66); p = 0.001), irrespective of aneurysm location. Subgroup-analysis revealed positive associations of surgical hematoma evacuation with outcome in subgroups with larger PH volumes (>10 ml; OR (95%CI): 1.39 (1.09–1.79)), frontal PH location (OR 1.59 (1.14–2.23)), and early surgery (within 600 min after onset; OR 1.42 (1.03–1.94)). Conclusions: Concomitant PH occurs frequently in patients with SAH and is associated with functional impairment after 1 year. Surgical evacuation of PH may improve outcomes in these patients, irrespective of aneurysm-location.
CRIS-Team Scopus Importer:2020-11-27
Keywords: Cerebral hemorrhage; complications; intracerebral hemorrahage; subarachnoid hemorrhage; surgery; treatment

Parenchymatous hemorrhage is associated with unfavorable longterm outcome in patients with atraumatic subarachnoid hemorrhage - Gerner, Stefan; Kuramatsu, J.; Reichl, J.; Eyüpoglu, Ilker Yasin; Buchfelder, Michael; Dörfler, Arnd; Struffert, Tobias; Schwab, Sibylle; Huttner, Hagen (2017)
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Parenting stress and the reliability of parental information in the diagnostics of children and adolescents with symptoms of psychiatric and behavioral disorders - Irlbauer-Müller, Viktoria; Eichler, Anna; Stemmler, Mark; Moll, Gunther; Kratz, Oliver (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2017)
Information from parents is regularly used in the diagnostic process of children and adolescents with psychiatric symptoms. But the reliability of this information is debatable, because the parents' own stress can distort their perceptions of the child's symptoms.For each of N = 68 children and adolescents (11-18 years) who were using mental health services for the first time, we evaluated the ratings of a parent and a professional clinician (internalizing, externalizing symptoms, total-problem score). In addition, parenting stress was scored on the Eltern-Belastungs-Inventars (EBI, Tröster, 2011), which measures both child-related stress and parent-related stress as well as total stress.Highly stressed parent ratings differed more from the clinicians' ratings than the ratings of less stressed parents. Additionally, correlations showed that higher parenting stress resulted in larger differences between the parent's and the clinician's assessments. Multiple regressions proved the predictive value of child-caused parenting stress for these differences. These results apply for internalizing symptoms, externalizing symptoms, and total-problem score.Parenting stress should be evaluated systematically in order to carefully assess the value of the information from parents and to determine how it should be included in diagnostic and therapeutical decisions.
EVALuna2:23890

PASSED: Brain atrophy in non-demented individuals in a long-term longitudinal study from two independent cohorts - Haas, Anna-Lena; Olm, Pauline; Utz, Janine; Siegmann, Eva-Maria; Spitzer, Philipp; Florvaag, Anna; Schmidt, Manuel; Dörfler, Arnd; Lewczuk, Piotr; Kornhuber, Johannes; Maler, Juan Manuel; Oberstein, Timo (Frontiers in Aging Neuroscience, 2023)
Introduction: Alzheimer’s disease (AD) is indicated by a decrease in amyloid beta 42 (Aβ42) level or the Aβ42/Aβ40 ratio, and by increased levels of Tau with phosphorylated threonine at position 181 (pTau181) in cerebrospinal fluid (CSF) years before the onset of clinical symptoms. However, once only pTau181 is increased, cognitive decline in individuals with subjective or mild cognitive impairment is slowed compared to individuals with AD. Instead of a decrease in Aβ42 levels, an increase in Aβ42 was observed in these individuals, leading to the proposal to refer to them as nondemented subjects with increased pTau-levels and Aβ surge with subtle cognitive deterioration (PASSED). In this study, we determined the longitudinal atrophy rates of AD, PASSED, and Biomarker-negative nondemented individuals of two independent cohorts to determine whether these groups can be distinguished by their longitudinal atrophy patterns or rates. Methods: Depending on their CSF-levels of pTau 181 (T), total Tau (tTau, N), Aβ42 or ratio of Aβ42/Aβ40 (A), 185 non-demented subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 62 non-demented subjects from Erlangen AD cohort were assigned to an ATN group (A–T–N–, A–T+N±, A+T–N±and A+T+N±) and underwent T1-weighted structural magnetic resonance imaging (sMRI). Longitudinal grey matter (GM) atrophy patterns were assessed with voxel-based morphometry (VBM) using the cat12 toolbox on spm12 (statistical parametric mapping) of MRI scans from individuals in the ADNI cohort with a mean follow-up of 2 and 5 years, respectively. The annualized atrophy rate for individuals in the Erlangen cohort was determined using region of interest analysis (ROI) in terms of a confirmatory analysis. Results: In the A–T+N± group, VBM did not identify any brain region that showed greater longitudinal atrophy than the A+T+N±, A+T+N± or biomarker negative control group. In contrast, marked longitudinal atrophy in the temporal lobe was evident in the A+T–N± group compared with A+T–N± and biomarker-negative subjects. The ROI in the angular gyrus identified by VBM analysis of the ADNI cohort did not discriminate better than the hippocampal volume and atrophy rate between AD and PASSED in the confirmatory analysis. Discussion: In this study, nondemented subjects with PASSED did not show a unique longitudinal atrophy pattern in comparison to nondemented subjects with AD. The nonsignificant atrophy rate compared with controls suggests that increased pTau181-levels without concomitant amyloidopathy did not indicate a neurodegenerative disorder.
CRIS-Team Scopus Importer:2023-03-24
Keywords: Alzheimer disease/physiopathology*; amyloid beta-peptides/cerebrospinal fluid*; ATN classification; longitudinal studies; magnetic resonance imaging; medial temporal lobe; SNAP; tau proteins/cerebrospinal fluid*

Patienten mit Alkoholstörungen im Kontext der Lebertransplantation - Erim, Yesim; Beckmann, M. B.; Beckebaum, Susanne; Paul, Andreas; Senf, Wolfgang (Ärztliche Psychotherapie und Psychosomatische Medizin, 2010)

Patient related factors influencing the utilization of the psycho-oncology service - Schieber, Katharina; Madl, Martina; Paslakis, Georgios; Erim, Yesim (2018)
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Patient-reported non-adherence and immunosuppressant trough levels are associated with rejection after renal transplantation - Scheel, Jennifer; Reber, Sandra Therese; Stößel, Lisa; Waldmann, Elisabeth; Jank, Sabine; Eckardt, Kai-Uwe; Grundmann, Franziska; Vitinius, Frank; De Zwaan, Martina; Bertram, Anna; Erim, Yesim (BMC Nephrology, 2017)
EVALuna2:3948

Patient's Experience with Living Donation: A Questionnaire-Based Survey of 144 Living Kidney Donors - Schieber, Katharina; Gaag, Sonja; Heller, Katharina; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2018)
Keywords: evaluation; consequences; psychosocial consequences; living donation; living kidney donation

Pavlovian-to-instrumental transfer in Anorexia Nervosa: A pilot study on conditioned learning and instrumental responding to low- and high-calorie food stimuli - Vogel, Verena; Dittrich, Marie; Horndasch, Stefanie; Kratz, Oliver; Moll, Gunther; Erim, Yesim; Paslakis, Georgios; Rauh, Elisabeth; Steins-Loeber, Sabine (European Journal of Neuroscience, 2019)
Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder-compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food-related conditioned responses and the influence of conditioned low-calorie and high-calorie food stimuli on instrumental responding for different foods. A Pavlovian-to-instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE-Q, EDI-2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low- and high-calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low-calorie food increased with increasing severity of eating disorder psychopathology suggesting weight-loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward-associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.
CRIS-Team Scopus Importer:2019-11-19
Keywords: appetitive conditioning; eating disorders; goal-directed behaviour; instrumental responding; PIT effect

Perceived discrimination among Syrian refugees in Germany and its associations with mental health - Viazminsky, Andre; Borho, Andrea; Morawa, Eva; Schmitt, Gregor Martin; Erim, Yesim (Global Public Health, 2022)
Discrimination is a crucial post migratory stressor but there is little research on perceived discrimination by Syrian refugees. This study aims to assess self-reported discrimination by Syrian refugees with a residence permit in Germany, determine its forms, places, and predictors, and explore its possible relation with mental health. Sociodemographics, migration-specific characteristics, traumatic life events, quality of life, perceived discrimination, depression, generalised anxiety disorder, post-traumatic symptoms, and somatic distress were assessed among 116 participants. More than one-third of the participants perceived discrimination in low frequency, and in general, perceived discrimination was confined to treatment with less courtesy or respect. Unfair treatment was perceived mostly while searching for accommodation and in the neighbourhood. Refugees attributed their experiences to their lack of language skills prior to national, religious, and racial causes. Lower age, higher number of completed years of education, and symptoms of posttraumatic stress disorder were significantly and substantially associated with perceived discrimination. Anxiety symptoms, number of traumatic experiences and gender may also be regarded as relevant predictors of perceived discrimination. Health care professionals must be aware of the links between discrimination and symptoms of mental disorders. Policymakers should address discrimination as a key refugee issue and risk to mental health.
CRIS-Team WoS Importer:2022-01-28

Perceived post-migration discrimination: the perspective of adolescents with migration background - Borho, Andrea; Morawa, Eva; Schug, Caterina; Erim, Yesim (European Child & Adolescent Psychiatry, 2022)
Discrimination has a negative impact on mental health and wellbeing of persons affected. The aim of the present study was to investigate perceived discrimination of migrant adolescents. Focus groups with migrant adolescents were conducted, audio-recorded and transcribed verbatim. The transcripts were analyzed using the manifest qualitative content analysis by Mayring. The foci of interest (persons discriminated against and by whom, where and how the discrimination took place, which behavioral and emotional reactions the affected persons showed to the experiences and which reasons they assumed for the discrimination) were determined based on the pre-defined guideline, and inductive subcategories were extracted from the transcripts and grouped into main categories. Five focus groups with students with migration background (n = 35, 13 females, mean age: 18.78, SD = 2.26, range 16-24) were conducted. The adolescents in our focus groups and their acquaintances (families and friends) experienced discrimination in Germany in several forms (verbal and non-verbal), places and on an individual as well as institutional level, with an impact on their emotional well-being. To combat discrimination, culturally sensitive information must be provided on the part of those affected as well as their perpetrators.
CRIS-Team WoS Importer:2022-09-30

Perception and evaluation of women's bodies in adolescents and adults with anorexia nervosa - Horndasch, Stefanie; Heinrich, Hartmut; Kratz, Oliver; Mai, Sandra; Graap, Holmer; Moll, Gunther (European archives of psychiatry and clinical neuroscience, 2015)
Body image disturbance in anorexia nervosa (AN) has been widely studied with regard to the patient's own body, but little is known about perception of or attitude towards other women's bodies in AN. The aim of the present study was to investigate how 20 girls aged 12-18 years and 19 adult women suffering from AN compared to 37 healthy adolescent girls and women estimate weight and attractiveness of women's bodies belonging to different BMI categories (BMI 13.8-61.3 kg/m²). Weight and attractiveness ratings of the participant's own body and information on physical comparisons were obtained, and effects on others' weight and attractiveness ratings investigated. Differential evaluation processes were found: AN patients estimated other women's weight higher than control participants. Patients showed a bias towards assessing extremely underweight women as more attractive and normal weight and overweight women as less attractive than healthy girls and women. These effects were more pronounced in adult than in adolescent AN patients. The tendency to engage in physical comparison with others significantly correlated with weight as well as attractiveness ratings in patients. A logistic regression model encompassing own attractiveness ratings, attractiveness bias towards strongly underweight others' bodies and the interaction of this bias with age as predictors differentiated best between AN patients and controls. Our results indicate that females suffering from AN and healthy girls and women perceive other women's bodies differently. Assessment of others' weight and attractiveness may contribute to the maintenance of dysfunctional physical comparison processes.
EVALuna2:23873

Performance of scientific cameras with different sensor types in measuring dynamic processes in fluorescence microscopy. - Jung, Jasmin; Weisenburger, S; Albert, S; Gilbert, Daniel; Friedrich, Oliver; Eulenburg, Volker; Kornhuber, Johannes; Groemer, Teja W. (Microscopy research and technique, 2013)
The plethora of available scientific cameras of different types challenges the biologically oriented experimenter when picking the appropriate camera for his experiment. In this study, we chose to investigate camera performances in a typical nonsingle molecule situation in life sciences, that is, quantitative measurements of fluorescence intensity changes from video data with typically skewed intensity distributions. Here, intensity profile dynamics of pH-sensors upon triggered changes of pH-environments in living cells served as a model system. The following camera types were tested: sCMOS, CCD (scientific and nonscientific) and EM-CCD (back- and front-illuminated). We found that although the EM-CCD cameras achieved the best absolute spatial SNR (signal-to-noise ratio) values, the sCMOS was at least of equal performance when the spatial SNR was related to the effective dynamic range, and it was superior in terms of temporal SNR. In the measurements of triggered intensity changes, the sCMOS camera had the advantage that it used the smallest fraction of its dynamic range when depicting intensity changes, and thus featured the best SNR at full usage of its dynamic range.

Peripheral Acid Sphingomyelinase Activity Is Associated with Biomarkers and Phenotypes of Alcohol Use and Dependence in Patients and Healthy Controls - Mühle, Christiane; Weinland, Christian; Gulbins, Erich; Lenz, Bernd; Kornhuber, Johannes (International Journal of Molecular Sciences, 2018)
By catalyzing the hydrolysis of sphingomyelin into ceramide, acid sphingomyelinase (ASM) changes the local composition of the plasma membrane with effects on receptor-mediated signaling. Altered enzyme activities have been noted in common human diseases, including alcohol dependence. However, the underlying mechanisms remain largely unresolved. Blood samples were collected from early-abstinent alcohol-dependent in-patients (n[♂] = 113, n[♀] = 87) and matched healthy controls (n[♂] = 133, n[♀] = 107), and analyzed for routine blood parameters and serum ASM activity. We confirmed increased secretory ASM activities in alcohol-dependent patients compared to healthy control subjects, which decreased slightly during detoxification. ASM activity correlated positively with blood alcohol concentration, withdrawal severity, biomarkers of alcohol dependence (liver enzyme activities of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase; homocysteine, carbohydrate-deficient transferrin; mean corpuscular volume, and creatine kinase). ASM activity correlated negatively with leukocyte and thrombocyte counts. ASM and gamma-glutamyl transferase were also associated in healthy subjects. Most effects were similar for males and females with different strengths. We describe previously unreported associations between ASM activity and markers of liver damage and myelosuppression. Further research should investigate whether this relationship is causal, or whether these parameters are part of a common pathway in order to gain insights into underlying mechanisms and develop clinical applications.
EVALuna2:211614

PERIPHERAL PULSE MEASUREMENTS FOR THE DETECTION OF SILENT ATRIAL FIBRILLATION: RESULTS FROM THE PROSPECTIVE, CONTROLLED TRIAL "KNOW YOUR PULSE POST STROKE" - Kallmünzer, Bernd; Macha, Kosmas; Wang, Ruihao; Siedler, Gabriela; Stoll, Svenja; Marsch, Armin; Gerner, Stefan; Winder, Klemens; Koehn, J.; Schwab, Stefan; Koehrmann, M. (INTERNATIONAL JOURNAL OF STROKE, 2020)
CRIS-Team WoS Importer:2021-01-22

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression - Brazdis, Razvan Marius; von Zimmermann, Claudia; Lenz, Bernd; Kornhuber, Johannes; Mühle, Christiane (International Journal of Molecular Sciences, 2024)
Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.
CRIS-Team Scopus Importer:2024-04-05
Keywords: affective disorder; anxiety; biomarker; GBA1; gene expression; major depressive disorder; MDD; PD; SNCA; UGCG

Personality driven alcohol and drug abuse: new mechanisms revealed - Skóra, Maria Nalberczak; Pattij, Tommy; Beroun, Anna; Kogias, Georgios; Mielenz, Dirk; de Vries, Taco; Radwanska, Kasia; Müller, Christian P. (Neuroscience and Biobehavioral Reviews, 2020)
While the majority of the regular consumers of alcohol controls their consumption well over life span and even takes instrumentalization benefits from it, a minority, but yet high total number of users develops an alcohol addiction. It has long been known that particular personality types are more addiction prone than others. Here we review recent progress in the understanding of neurobiological pathways that determine personality and facilitate drug abuse. Novel approaches to characterize personality traits leading to addiction proneness in social settings in mice are discussed. A common genetic and neurobiological base for the behavioural traits of sensation seeking or a depressed phenotype and escalating alcohol consumption are reviewed. Furthermore, recent progress on how social and cognitive factors, including impulsivity and decision making, act at brain level to make an individual more vulnerable to alcohol abuse, are discussed. Altogether, this review provides an update on brain mechanisms underlying a broad spectrum of personality traits that make an individual more prone to alcohol and drug abuse and addiction.
CRIS-Team Scopus Importer:2020-06-30
Keywords: addiction; alcohol; depression; drug abuse; drug instrumentalization; impulsivity; personality; sensation-seeking

Pharmacist-Led Medication Reviews to Identify and Collaboratively Resolve Drug-Related Problems in Psychiatry - A Controlled, Clinical Trial - Wolf, Carolin; Pauly, Anne; Mayr, Andreas; Groemer, Teja; Lenz, Bernd; Kornhuber, Johannes; Friedland, Kristina (PLoS ONE, 2015)
This prospective, controlled trial aimed to assess the effect of pharmacist-led medication reviews on the medication safety of psychiatric inpatients by the resolution of Drug-Related Problems (DRP). Both the therapy appropriateness measured with the Medication Appropriateness Index (MAI) and the number of unsolved DRP per patient were chosen as primary outcome measures.Depending on their time of admission, 269 psychiatric patients that were admitted to a psychiatric university hospital were allocated in control (09/2012-03/2013) or intervention group (05/2013-12/2013). In both groups, DRP were identified by comprehensive medication reviews by clinical pharmacists at admission, during the hospital stay, and at discharge. In the intervention group, recommendations for identified DRP were compiled by the pharmacists and discussed with the therapeutic team. In the control group, recommendations were not provided except for serious or life threatening DRP. As a primary outcome measure, the changes in therapy appropriateness from admission to discharge as well as from admission to three months after discharge (follow-up) assessed with the MAI were compared between both groups. The second primary outcome was the number of unsolved DRP per patient after completing the study protocol. The DRP type, the relevance and the potential of drugs to cause DRP were also evaluated.The intervention led to a reduced MAI score by 1.4 points per patient (95% confidence interval [CI]: 0.8-2.0) at discharge and 1.3 points (95% CI: 0.7-1.9) at follow-up compared with controls. The number of unsolved DRP in the intervention group was 1.8 (95% CI: 1.5-2.1) less than in control.The pharmaceutical medication reviews with interdisciplinary discussion of identified DRP appears to be a worthy strategy to improve medication safety in psychiatry as reflected by less unsolved DRP per patient and an enhanced appropriateness of therapy. The promising results of this trial likely warrant further research that evaluates direct clinical outcomes and health-related costs.Deutsches Register Klinischer Studien (DRKS), DRKS00006358.
EVALuna2:5531

Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells - Carpinteiro, Alexander; Edwards, Michael J.; Hoffmann, Markus; Kochs, Georg; Gripp, Barbara; Weigang, Sebastian; Adams, Constantin; Carpinteiro, Elisa; Gulbins, Anne; Keitsch, Simone; Sehl, Carolin; Soddemann, Matthias; et al. (Cell Reports Medicine, 2020)
The acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Here, we report that either pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram, or maprotiline or genetic downregulation of the enzyme prevents infection of cultured cells or freshy isolated human nasal epithelial cells with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vesicular stomatitis virus (VSV) pseudoviral particles (pp-VSV) presenting SARS-CoV-2 spike protein (pp-VSV-SARS-CoV-2 spike), a bona fide system mimicking SARS-CoV-2 infection. Infection activates acid sphingomyelinase and triggers a release of ceramide on the cell surface. Neutralization or consumption of surface ceramide reduces infection with pp-VSV-SARS-CoV-2 spike. Treating volunteers with a low dose of amitriptyline prevents infection of freshly isolated nasal epithelial cells with pp-VSV-SARS-CoV-2 spike. The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 infection.
CRIS-Team Scopus Importer:2020-12-04
Keywords: acid sphingomyelinase; amitriptyline; antidepressants; ceramide; escitalopram; fluoxetine; human nasal epithelial cells; infection; SARS-CoV-2

Pharmacological Inhibition of Amyloidogenic APP Processing and Knock-Down of APP in Primary Human Macrophages Impairs the Secretion of Cytokines - Spitzer, Philipp; Walter, Matthias; Göth, Caroline; Oberstein, Timo; Linning, Philipp; Knölker, Hans Joachim; Kornhuber, Johannes; Maler, Juan Manuel (Frontiers in Immunology, 2020)
It has been previously shown that the amyloid precursor protein (APP) support the innate immune defense as an immune receptor. Amyloid β (Aβ) peptides seem to have properties of an antimicrobial peptide and can act as opsonines. In APP-deficient mouse models, a reduced secretion of cytokines has been observed. Still, it is unclear whether this can be attributed to the lack of APP or to the missing secretion of Aβ peptides. We inhibited the secretion of Aβ peptides in primary human monocyte derived macrophages with the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine-t-butyl-ester (DAPT) or the β-secretase inhibitor GL-189. Alternatively, we knocked down APP by transfection with siRNA. We measured tumor necrosis factor α (TNFα), interleukin 6 (IL-6) and interleukin (IL-10) by enzyme linked immunosorbent assay (ELISA) and evaluated the phagocytotic activity by flow cytometry. We observed reduced concentrations of TNFα and IL-6 in the media of APPk/d macrophages and after inhibition of the β-, or γ-secretase, especially after additional immunological activation with lipopolysaccharide (LPS). Secretion of IL-10 was increased after pharmacological inhibition of APP processing when the macrophages were not immunologically activated but was decreased during LPS-induced inflammation in APPk/d macrophages. No changes of the phagocytotic activity were observed. We conclude that macrophage APP and Aβ peptides support the initiation of an immune response and are involved in the regulation of TNFα, IL-6, and IL-10 secretion by human monocyte-derived macrophages.
CRIS-Team Scopus Importer:2020-09-25
Keywords: Abeta; Alzheimer; amyloid; amyloid precursor protein; BACE; cytokine; immune system; secretase

Pharmacotherapy of schizophrenia: Mechanisms of antipsychotic accumulation, therapeutic action and failure - Chestnykh, Daria; Amato, Davide; Kornhuber, Johannes; Müller, Christian P. (Behavioural Brain Research, 2021)
Schizophrenia is a multi-dimensional disorder with a complex and mostly unknown etiology, leading to a severe decline in life quality. Antipsychotic drugs (APDs) remain beneficial interventions in the treatment of the disorder, but vary significantly in binding profile, clinical effects and adverse reactions. The present review summarizes the main principles of APD mechanisms of action with a particular focus on recent findings in APD accumulation and its role in the therapeutic efficacy and treatment failure. High and low doses of APDs were shown to be effective in different dimensions of antipsychotic-like behaviour in rodent models. Efficacy of the APDs correlates with high dopamine D2 receptor occupancy, which occurs quickly after drug administration. However, onset and peak of action are delayed up to several days or weeks. APD accumulation via acidic trapping in synaptic vesicles is considered to underlie the time course of APD action. Use-dependent exocytosis, co-release with dopamine and serotonin and inhibition of ion channels impact on the neuronal transmission and determine effects of APDs. Disruption in accumulating properties leads to diminished APD effects. In addition, long-term APD administration at therapeutic doses leads to treatment failure both in animal models and in humans. APD failure was associated with treatment induced neuroadaptations, including a decline in extracellular dopamine levels, dopamine transporter upregulation, and altered neuronal firing. However, enhanced synaptic vesicle release has also been reported. APD loss of efficacy may be reversed through inhibition of the dopamine transporter or switching the administration regimen from continuous to intermittent. Thus, manipulating the accumulation properties of APDs, changes in the administration regimen and doses, or co-administration with dopamine transporter inhibitors may be considered to yield benefits in the development of new effective strategies in the treatment of schizophrenia.
CRIS-Team Scopus Importer:2021-02-05
Keywords: Accumulation; Acidic trapping; Antipsychotics; Efficacy; Failure reversal; Treatment failure

Phenotype, neuropsychology and psychopathology of C9orf72 mutation carriers from the German FTLD-Consortium - Diehl-Schmid, J.; Rossmeier, C.; Straub, S.; Kelm, T.; Kornhuber, Johannes; Fliessbach, K.; Grimmer, T.; Kehl, A.; Otto, M.; Schroeter, M. L. (2016)
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Physical Activity and Body Composition Are Associated With Severity and Risk of Depression, and Serum Lipids - von Zimmermann, Claudia; Winkelmann, Merle; Richter-Schmidinger, Tanja; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Frontiers in Psychiatry, 2020)
Background: Physical activity and a healthy body composition are said to reduce the risk of major depressive disorder. Nonetheless, deeper insight is needed into which specific forms of physical activity (and their relation to body composition) are effective in improving and preventing depressive symptoms. Methods: We compared different self-reported physical activities of the Global Physical Activity Questionnaire and body composition measures between patients with a current major depressive episode (MDE; N = 130) and healthy control subjects (N = 61). These parameters were also tested for correlations with depression severity and serum lipid levels in patients and controls. Results: Patients with a current MDE reported significantly fewer hours spent on total physical activity, walking or bicycling for travel, and vigorous-intensity activities at leisure than healthy control subjects. More time spent on vigorous-intensity activities at work, less time spent on walking or bicycling for travel, higher body fat mass, and lower body muscle mass correlated significantly with stronger depression severity. Physical activity and body measures correlated significantly with serum lipid levels. Limitations: Self-reports of physical activity, only short-term follow-up of 20 days, cross-sectional study design without examination of causal role of exercise. Conclusions: More time spent on traveling by foot or by bike is especially associated with a lower risk of and milder depression. These results highlight the differential role of physical activity in depression.
CRIS-Team Scopus Importer:2020-06-30
Keywords: body composition; depression; mental health; physical activities and sports; serum lipid concentration

Physical activity and energy expenditure during depressive episodes of major depression - Wielopolski, Jan; Reich, Karin; Clepce, Marion; Fischer, Marie; Sperling, Wolfgang; Kornhuber, Johannes; Thürauf, Norbert (Journal of Affective Disorders, 2015)
Recent data suggest a substantial association between physical activity and depressive symptoms, but there is a lack of research evaluating the physical activity levels in patients suffering from unipolar depression across different stages of disease in an objective way. The aim of the present pilot study was to objectively examine physical activity levels of this patient group compared to healthy controls.Physical activity performance of 19 patients with major depressive episode and 19 healthy controls was assessed at three different time points using a multisensory armband device (SenseWear® Pro3 Armband) and was reported as total energy expenditure (TEE), active energy expenditure (EE), metabolic equivalents (METs), physical activity (PA) and time of lying down (LD), in each case over 24h.Over all measurements, depressive patients presented a significantly lower mean TEE and EE over 24h. Moreover, the patient group showed significantly shorter duration of PA and lower average MET over 24h. When depressive symptoms abated, physical activity parameters significantly increased in the patient group. Correlation analyses demonstrated a significant relation between depressive status/anhedonia and parameters of physical activity, especially in healthy subjects.Results represented valid data for inpatients only.Acute unipolar depression was associated with a significantly lower level of physical activity and showed a significant increase in parallel to clinical improvement. Electronic monitoring of physical activity may be an additional tool for evaluating and controlling therapeutic effects.
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Physiological Concentrations of Amyloid Beta Regulate Recycling of Synaptic Vesicles via Alpha7 Acetylcholine Receptor and CDK5/Calcineurin Signaling - Lazarevic, Vesna; Fienko, Sandra; Andres-Alonso, Maria; Anni, Daniela; Ivanova, Daniela; Montenegro-Venegas, Carolina; Gundelfinger, Eckart D.; Cousin, Michael A.; Fejtova, Anna (Frontiers in Molecular Neuroscience, 2017)
Despite the central role of amyloid β (Aβ) peptide in the etiopathogenesis of Alzheimer's disease (AD), its physiological function in healthy brain is still debated. It is well established that elevated levels of Aβ induce synaptic depression and dismantling, connected with neurotoxicity and neuronal loss. Growing evidence suggests a positive regulatory effect of Aβ on synaptic function and cognition; however the exact cellular and molecular correlates are still unclear. In this work, we tested the effect of physiological concentrations of Aβ species of endogenous origin on neurotransmitter release in rat cortical and hippocampal neurons grown in dissociated cultures. Modulation of production and degradation of the endogenous Aβ species as well as applications of the synthetic rodent Aβ40and Aβ42affected efficacy of neurotransmitter release from individual presynapses. Low picomolar Aβ40and Aβ42increased, while Aβ depletion or application of low micromolar concentration decreased synaptic vesicle recycling, showing a hormetic effect of Aβ on neurotransmitter release. These Aβ-mediated modulations required functional alpha7 acetylcholine receptors as well as extracellular and intracellular calcium, involved regulation of CDK5 and calcineurin signaling and increased recycling of synaptic vesicles. These data indicate that Aβ regulates neurotransmitter release from presynapse and suggest that failure of the normal physiological function of Aβ in the fine-tuning of SV cycling could disrupt synaptic function and homeostasis, which would, eventually, lead to cognitive decline and neurodegeneration.
EVALuna2:33406

Physiological effects of cigarette smoking in the limbic system revealed by 3 tesla magnetic resonance spectroscopy - Mennecke, Angelika; Gossler, Andrea; Hammen, Thilo; Dörfler, Arnd; Stadlbauer, Andreas; Roesch, Julie; Kornhuber, Johannes; Bleich, Stefan; Dölken, Marc; Thürauf, Norbert (Journal of Neural Transmission, 2014)
Several studies and recent models of effects of nicotine, the main addictive and psychoactive component in tobacco, point to action of the drug on the limbic system during maintenance of addiction, either direct or indirect via projections from the ventral tegmental area. The objective of this study was to demonstrate physiological effects of cigarette smoking on the hippocampus and the grey matter of the dorsal anterior cingulate cortex in the human brain with regard to addiction and withdrawal. This aim was achieved by group comparisons of results of magnetic resonance spectroscopy between non-smokers, smokers and smokers during withdrawal. 12 smokers and 12 non-smokers were measured with single voxel proton magnetic resonance spectroscopy for total N-acetyl aspartate, glutamate and glutamine, choline-containing compounds, myo-inositol and total creatine in the right and the left hippocampus and in the right and the left dorsal anterior cingulate cortex. Smokers were examined twice, first during regular cigarette smoking and second on the third day of nicotine withdrawal. The ratios to total creatine were used for better reliability. In our study, Glx/tCr was significantly increased and tCho/tCr was significantly decreased in the left cingulate cortex in smokers compared to non-smokers (p = 0.01, both). Six out of seven smokers showed normalization of the Glx/tCr in the left cingulate cortex during withdrawal. Although these results are preliminary due to the small sample size, our results confirm the assumption that cigarette smoking interferes directly or indirectly with the glutamate circuit in the dorsal anterior cingulate cortex.
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Plasma concentrations of the amyloid-? peptides in young volunteers: the influence of the APOE genotype - Zimmermann, Rüdiger; Huber, Ellen; Schamber, Christine; Lelental, Natalia; Mroczko, Barbara; Brandner, Sebastian; Maler, Juan Manuel; Oberstein, Timo; Szmitkowski, Maciej; Rauh, Manfred; Kornhuber, Johannes; Lewczuk, Piotr (Journal of Alzheimer's Disease, 2014)
Changes in the concentrations of amyloid-? (A?) in the body fluids are the earliest alterations observed in Alzheimer's disease (AD), however, there is a lack of data about how early these alterations occur, before the onset of the clinical symptoms. APOE genotype is the most recognized genetic risk/protective factor of AD, meaning that a group of non-demented persons carrying ?4 allele is enriched in the subjects who will develop AD, compared to the group of non-carriers. Therefore, we studied the plasma concentrations of A? peptides (A?1-42, A?1-40, A?x-42, and A?x-40), and the APOE genotype in 173 young volunteers (average age, 28 ± 7.6 years) without memory deficits, in order to see whether the non-demented group of subjects at risk already characterize with A? changes three-to-four decades before the age at which dementia usually occurs. We did not find statistically significant differences among the groups of ?4 carriers, ?3 homozygotes, and ?2 carriers. We conclude that the APOE genotype does not influence the metabolism of the A? peptides in young persons without memory deficits.
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Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer’s disease pathology and clinical disease progression - Clark, Christopher; Lewczuk, Piotr; Kornhuber, Johannes; Richiardi, Jonas; Maréchal, Bénédicte; Karikari, Thomas K.; Blennow, Kaj; Zetterberg, Henrik; Popp, Julius (Alzheimer's Research and Therapy, 2021)
Background: To assess the performance of plasma neurofilament light (NfL) and phosphorylated tau 181 (p-tau181) to inform about cerebral Alzheimer’s disease (AD) pathology and predict clinical progression in a memory clinic setting. Methods: Plasma NfL and p-tau181, along with established cerebrospinal fluid (CSF) biomarkers of AD pathology, were measured in participants with normal cognition (CN) and memory clinic patients with cognitive impairment (mild cognitive impairment and dementia, CI). Clinical and neuropsychological assessments were performed at inclusion and follow-up visits at 18 and 36 months. Multivariate analysis assessed associations of plasma NfL and p-tau181 levels with AD, single CSF biomarkers, hippocampal volume, and clinical measures of disease progression. Results: Plasma NfL levels were higher in CN participants with an AD CSF profile (defined by a CSF p-tau181/Aβ1–42 > 0.0779) as compared with CN non-AD, while p-tau181 plasma levels were higher in CI patients with AD. Plasma NfL levels correlated with CSF tau and p-tau181 in CN, and with CSF tau in CI patients. Plasma p-tau181 correlated with CSF p-tau181 in CN and with CSF tau, p-tau181, Aβ1–42, and Aβ1–42/Aβ1–40 in CI participants. Compared with a reference model, adding plasma p-tau181 improved the prediction of AD in CI patients while adding NfL did not. Adding p-tau181, but not NfL levels, to a reference model improved prediction of cognitive decline in CI participants. Conclusion: Plasma NfL indicates neurodegeneration while plasma p-tau181 levels can serve as a biomarker of cerebral AD pathology and cognitive decline. Their predictive performance depends on the presence of cognitive impairment.
CRIS-Team Scopus Importer:2021-04-09
Keywords: Alzheimer’s; Biomarkers; Neurofilament light; p-tau181; Plasma

Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease - Lewczuk, Piotr; Ermann, Natalia; Andreasson, Ulf; Schultheis, Christian; Podhorna, Jana; Spitzer, Philipp; Maler, Juan Manuel; Kornhuber, Johannes; Blennow, Kaj; Zetterberg, Henrik (Alzheimer's Research and Therapy, 2018)
BACKGROUND: A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer's disease (AD). METHODS: With a single molecule array method (Simoa, Quanterix), plasma NfL concentrations were measured in 99 subjects with AD at the stage of mild cognitive impairment (MCI-AD; n = 25) or at the stage of early dementia (ADD; n = 33), and in nondemented controls (n = 41); in all patients, the clinical diagnoses were in accordance with the results of the four core cerebrospinal fluid (CSF) biomarkers (amyloid β (Aβ)1-42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm. The influence of preanalytical storage procedures on the NfL in plasma was tested on samples exposed to six different conditions. RESULTS: NfL concentrations significantly increased in the samples exposed to more than one freezing/thawing cycle, and in those stored for 5 days at room temperature or at 4 °C. Compared with the control group of nondemented subjects (22.0 ± 12.4 pg/mL), the unadjusted plasma NfL concentration was highly significantly higher in the MCI-AD group (38.1 ± 15.9 pg/mL, p < 0.005) and even further elevated in the ADD group (49.1 ± 28.4 pg/mL; p < 0.001). A significant association between NfL and age (ρ = 0.65, p < 0.001) was observed; after correcting for age, the difference in NfL concentrations between AD and controls remained significant (p = 0.044). At the cutoff value of 25.7 pg/mL, unconditional sensitivity, specificity, and accuracy were 0.84, 0.78, and 0.82, respectively. Unadjusted correlation between plasma NfL and Mini Mental State Examination (MMSE) across all patients was moderate but significant (r = -0.49, p < 0.001). We observed an overall significant correlation between plasma NfL and the CSF biomarkers, but this correlation was not observed within the diagnostic groups. CONCLUSIONS: This study confirms increased concentrations of plasma NfL in patients with Alzheimer's disease compared with nondemented controls.
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Playback of 50-kHz ultrasonic vocalizations overcomes psychomotor deficits induced by sub-chronic haloperidol treatment in rats - Melo-Thomas, Liana; Tonelli, Luan C.; Müller, Christian P.; Woehr, Markus; Schwarting, Rainer K. W. (Psychopharmacology, 2020)
Rationale In rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism. Objectives We investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen. Methods In phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm. Results Sub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback. Conclusions This study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.
CRIS-Team WoS Importer:2020-05-29

Playing Tetris Lets You Rate Odors as Less Intense - Schadll, Stephan; Rodriguez-Raecke, Rea; Heim, Lennart; Freiherr, Jessica (Frontiers in Psychology, 2021)
Overweight and obesity are considered a huge problem in modern societies. Previous studies have shown that people who are regularly distracted by playing videogames or watching TV while eating are more likely to be overweight and that the number of people that are gaming worldwide is rising. Further, it has been established that both, watching TV or playing video games lead to an increased snack intake and a lower rating of perceived taste intensity. Since flavor perception is accomplished not only by the sense of taste but also the sense of smell, we investigated the influence of cognitive load created by playing a video game on odor intensity perception. The participants played a low or high difficulty version of Tetris while presented with odors of food and non-food items. A higher skin conductance response (SCR) along with a decrease in task performance verified that the higher difficulty level leads to a higher cognitive load. Our behavioral data indicates a significant decrease in intensity estimates of food odors and non-food odors during the high compared to low cognitive load condition. We conclude that odor intensity estimation is influenced by real-life cognitive tasks which might in turn lead to overeating while distracted.
CRIS-Team WoS Importer:2021-08-06

PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment - Kleineidam, Luca; Chouraki, Vincent; Próchnicki, Tomasz; van der Lee, Sven J.; Madrid-Márquez, Laura; Wagner-Thelen, Holger; Karaca, Ilker; Weinhold, Leonie; Wolfsgruber, Steffen; Boland, Anne; Martino Adami, Pamela V.; Lewczuk, Piotr; et al. (Acta Neuropathologica, 2020)
A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer's disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau181, total tau, and Aβ1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau181 levels in CSF. The effect size of the association of p.P522R with the cognitive decline and pTau181 was similar to that of APOE-ε4, the strongest genetic risk factor for AD. Interestingly, the protective effect of p.P522R was more pronounced in MCI patients with low Aβ1-42 levels suggesting a role of PLCG2 in the response to amyloid pathology. In line with this hypothesis, we observed no protective effect of the PLCG2 variant on the cognitive decline in population-based studies probably due to the lower prevalence of amyloid positivity in these samples compared to MCI patients. Concerning the potential biological underpinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD.
CRIS-Team Scopus Importer:2020-06-02
Keywords: Alzheimer’s disease; Cognitive decline; Mild cognitive impairment; Phospholipase C gamma 2; PLCG2

PLD3 in non-familial Alzheimer's disease - Heilmann, Stefanie; Drichel, Dmitriy; Clarimon, Jordi; Fernandez, Victoria; Lacour, Andre; Wagner, Holger; Thelen, Mathias; Hernandez, Isabel; Fortea, Juan; Alegret, Montserrat; Blesa, Rafael; Mauleon, Ana; et al. (Nature, 2015)
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Poly-GP in cerebrospinal fluid linksC9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD - Lehmer, Carina; Oeckl, Patrick; Weishaupt, Jochen H.; Volk, Alexander E.; Diehl-Schmid, Janine; Schroeter, Matthias L.; Lauer, Martin; Kornhuber, Johannes; Levin, Johannes; Fassbender, Klaus; Landwehrmeyer, Bernhard; Schludi, Martin H.; et al. (Embo Molecular Medicine, 2017)
TheC9orf72GGGGCC repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). Non-conventional repeat translation results in five dipeptide repeat proteins (DPRs), but their clinical utility, overall significance, and temporal course in the pathogenesis of c9ALS/FTD are unclear, although animal models support a gain-of-function mechanism. Here, we established a poly-GP immunoassay from cerebrospinal fluid (CSF) to identify and characterizeC9orf72patients. Significant poly-GP levels were already detectable in asymptomaticC9orf72mutation carriers compared to healthy controls and patients with other neurodegenerative diseases. The poly-GP levels in asymptomatic carriers were similar to symptomatic c9ALS/FTD cases. Poly-GP levels were not correlated with disease onset, clinical scores, and CSF levels of neurofilaments as a marker for axonal damage. Poly-GP determination in CSF revealed aC9orf72mutation carrier in our cohort and may thus be used as a diagnostic marker in addition to genetic testing to screen patients. Presymptomatic expression of poly-GP and likely other DPR species may contribute to disease onset and thus represents an alluring therapeutic target.
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Polytetrafluoroethylene (PTFE) suture vs fiberwire and polypropylene in flexor tendon repair - Polykandriotis, Elias; Ruppe, Florian; Niederkorn, Miriam; Polykandriotis, Ektor; Bräuer, Lars; Horch, Raymund E.; Arkudas, Andreas; Grüner, Johanna (Archives of Orthopaedic and Trauma Surgery, 2021)
Background In this study, we evaluate the value of novel suture material based on monofilamentous-extruded polyfluoroethylene (PTFE) compared to polypropylene (PPL) and Fiberwire (FW). Materials and methods 60 flexor tendons were harvested from fresh cadaveric upper extremities. 4-0 sutures strands were used in the PPL, FW and PTFE group. Knotting properties and mechanical characteristics of the suture materials were evaluated. A 4-strand locked cruciate (Adelaide) or a 6-strand (M-Tang) suture technique was applied as core sutures for a tendon repair. Two-way ANOVA tests were performed with the Bonferroni correction. Results Stable knotting was achieved with 5 throws with the PPL material, 7 throws for FW and 9 throws for PTFE. In the PPL group, linear tensile strength was 45.92 +/- 12.53 N, in the FW group 80.11 +/- 18.34 N and in the PTFE group 76.16 +/- 29.10 N. FW and PTFE are significantly stronger than PPL but show no significant difference among each other. Similar results were obtained in the subgroup comparisons for different repair techniques. The Adelaide and the M-Tang knotting technique showed no significant difference. Conclusion Fiberwire showed superior handling and knotting properties in comparison to PTFE. However, PTFE allows easier approximation of the stumps. In both, M-Tang and Adelaide repairs, PTFE was equal to FW in terms of repair strength. Both PTFE and FW provide for a robust tendon repair so that early active motion regimens for rehabilitation can be applied.
CRIS-Team WoS Importer:2021-05-07

Possible second motor neuron damage in neuromyelitis optica - Laemmer, A. B.; Maihöfner, Christian; Gölitz, Philipp; Schwab, Sibylle; Lee, D. H.; Linker, R. A.; Schramm, Axel (Clinical Neurophysiology, 2014)
EVALuna2:22245

Postexcitatory inhibition after transcranial magnetic stimulation of the motor cortex in patients with drug-induced parkinsonism and in healthy individuals - Masur, Harald; Althoff, Susanne; Erim, Yesim; Oberwittler, Christoph; Hornung, Wilhelm Peter (International Clinical Psychopharmacology, 1998)
Keywords: drug-induced parkinsonism; non-invasive magnetic stimulation of the brain; Parkinson's disease; postexcitatory inhibition; silent period

Posttraumatic stress and motivators of refugee aid volunteers and fulltime employees - Georgiadou, Ekaterini; Grimm, Theresa; Erim, Yesim (JOURNAL OF PSYCHOSOMATIC RESEARCH, 2019)
CRIS-Team WoS Importer:2019-06-21

Posttraumatic stress disorder after lung and heart transplantation - Erim, Yesim; Beckmann, M. B.; Sommerwerck, U.; Marggraf, G.; Azhari, P.; Senf, W. (Transplantationsmedizin, 2009)

Posttraumatic Stress Disorder, Quality of Life, and the Subjective Experience in Liver Transplant Recipients. - Erim, Yesim; Paslakis, Georgios; Beckmann, Mingo; Beckebaum, Susanne; Klein, Christian; Gräf, Jan (Progress in Transplantation, 2018)

Prävalenz und Prädiktoren für Rauschtrinken – Querschnittsbefragung repräsentativ für Niedersachsen - Donath, Carolin; Sack, Carolin; Pendergrass, Anna; Weiss, Maren; Baier, Dirk (Sucht, 2019)

Predicting attention deficit hyperactivity disorder using pregnancy and birth characteristics - Schwenke, Eva; Fasching, Peter; Faschingbauer, Florian; Pretscher, Jutta; Kehl, Sven; Peretz, Roberta; Keller, Andrea; Häberle, Lothar; Eichler, Anna; Irlbauer-Müller, Viktoria; Dammer, Ulf; Beckmann, Matthias; et al. (Archives of Gynecology and Obstetrics, 2018)
PURPOSE: The aim of this study was to evaluate maternal, prenatal, perinatal, and postpartum parameters as risk factors for the later development of an attention deficit hyperactivity disorder (ADHD) in the child. METHODS: Women who had given birth at Erlangen University Hospital between 1996 and 1999 were sent a questionnaire in 2009. The results of the questionnaire were correlated with the prospectively collected data for the births in 1996-1999. RESULTS: A total of 573 mother and child pairs were analyzed. Forty-four of the mothers reported that their child had ADHD (7.7%). No significant associations were found for the following parameters: mother's age; mother's educational level; number of the pregnancy; maternal weight before and at the end of pregnancy; mother's height; alcohol consumption during pregnancy; mode of delivery; gestational week; birthweight; umbilical artery blood values; Apgar score at 5 and 10 min; or breastfeeding. The parameters of smoking in pregnancy and an Apgar score lower than 7 after 1 min were significantly associated with a risk for later development of ADHD. CONCLUSIONS: This analysis of maternal, prenatal, perinatal, and postnatal parameters found that smoking in pregnancy and a low Apgar score 1 min after birth are associated with a significantly greater risk for the development of ADHD. Beyond the question of the causal mechanism involved, this is a relevant finding, since smoking during pregnancy is a preventable risk factor.
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Predicting disease progression in behavioral variant frontotemporal dementia - Anderl-Straub, Sarah; Lausser, Ludwig; Lombardi, Jolina; Uttner, Ingo; Fassbender, Klaus; Fliessbach, Klaus; Huppertz, Hans-Jurgen; Jahn, Holger; Kornhuber, Johannes; Obrig, Hellmuth; Schneider, Anja; Semler, Elisa; et al. (Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, 2021)
Introduction The behavioral variant of frontotemporal dementia (bvFTD) is a rare neurodegenerative disease. Reliable predictors of disease progression have not been sufficiently identified. We investigated multivariate magnetic resonance imaging (MRI) biomarker profiles for their predictive value of individual decline. Methods One hundred five bvFTD patients were recruited from the German frontotemporal lobar degeneration (FTLD) consortium study. After defining two groups ("fast progressors" vs. "slow progressors"), we investigated the predictive value of MR brain volumes for disease progression rates performing exhaustive screenings with multivariate classification models. Results We identified areas that predict disease progression rate within 1 year. Prediction measures revealed an overall accuracy of 80% across our 50 top classification models. Especially the pallidum, middle temporal gyrus, inferior frontal gyrus, cingulate gyrus, middle orbitofrontal gyrus, and insula occurred in these models. Discussion Based on the revealed marker combinations an individual prognosis seems to be feasible. This might be used in clinical studies on an individualized progression model.
CRIS-Team WoS Importer:2022-01-07

Prediction of major depressive disorder onset in college students - Ebert, David; Buntrock, Claudia; Mortier, Philippe; Auerbach, Randy; Weisel, Kiona K.; Kessler, Ronald C.; Cuijpers, Pim; Green, Jennifer G.; Kiekens, Glenn; Nock, Matthew K.; Demyttenaere, Koen; Bruffaerts, Ronny (Depression and Anxiety, 2019)
Background: Major depressive disorder (MDD) in college students is associated with substantial burden. Aims: To assess 1-year incidence of MDD among incoming freshmen and predictors of MDD-incidence in a representative sample of students. Method: Prospective cohort study of first-year college students (baseline: n = 2,519, 1-year follow-up: n = 958). Results: The incidence of MDD within the first year of college was 6.9% (SE = 0.8). The most important individual-level predictors of onset were prior suicide plans and/or attempts (OR = 9.5). The strongest population-level baseline predictors were history of childhood–adolescent trauma, stressful experience in the past 12 months, parental psychopathology, and other 12-month mental disorder. Multivariate cross-validated prediction (cross-validated AUC = 0.73) suggest that 36.1% of incident MDD cases in a replication sample would occur among the 10% of students at highest predicted risk (24.5% predicted incidence in this highest-risk subgroup). Conclusions: Screening at college entrance is a promising strategy to identify students at risk of MDD onset, which may improve the development and deployment of targeted preventive interventions.
CRIS-Team Scopus Importer:2019-05-02
Keywords: depression; epidemiology; health services; mood disorders; suicide/self-harm

Prediction of response to total sleep deprivation by autonomic heart rate parameters? - Rechlin, Thomas; Hegmann, Harald; Weis, Maria; Stemmler, Mark; Claus, Detlef; Kaschka, Wolfgang (Biological Psychiatry, 1995)
Keywords: Sleep deprivation; heart rate variability; autonomic parameters

Predictors for successful psychotherapy: Does migration status matter? - Kobel, Friederike; Erim, Yesim; Morawa, Eva (PLoS ONE, 2021)
Background We investigated, if migration status, and additional sociodemographic and clinical factors, are associated with somatization and depressiveness at admission and with remission after inpatient psychotherapy. Methods Multiple linear and binary logistic regression analyses were used to identify predictors for severity of somatoform and depressive symptoms at admission of inpatient psychotherapy (T0), and for remission after inpatient psychotherapy (T1). We tested the association between symptoms concerning somatization (PHQ-15: Patient-Health-Questionnaire Somatization Module) and depression (PHQ-9: Patient-Health-Questionnaire Depression Module) and several sociodemographic and clinical factors in 263 patients at admission. For remission after treatment, we additionally included severity of symptoms at admission, number of diagnoses and duration of treatment in the regression models. Remission after treatment was defined as response plus a post value of less than 10 points in the respective questionnaire. Clinical relevance was interpreted using effect sizes (regression coefficients, Odds Ratio (OR)) and Confidence Intervals (CI). Findings Significant and clinically relevant predictors for high symptom severity at T0 were lower education (β = -0.13, p = 0.04), pretreatment(s) (β = 0.205, p = 0.002) and migration status (β = 0.139, p = 0.023) for somatization, and potential clinically relevant predictors (|β|>0.1) for depression were living alone (β = -0.116, p = 0.083), pretreatment(s) (β = 0.118, p = 0.071) and migration status (β = 0.113, p = 0.069). At T1 patients with pretreatment(s) (OR = 0.284 [95% CI: 0.144, 0.560], p<0.001) and multiple diagnoses (OR = 0.678 [95% CI: 0.472, 0.973], p = 0.035) were significantly and clinically relevant less likely to show a remission of depressive symptoms. In addition, a potentially clinically meaningful effect of migration status on remission of depressive symptoms (OR = 0.562 [95% CI: 0.264, 1.198], p = 0.136) cannot be ruled out. For somatoform symptoms pretreatment(s) (OR = 0.403, [95% CI: 0.156, 1.041], p = 0.061) and education (OR = 1.603, [95% CI: 0.670, 3.839], p = 0.289) may be regarded as clinically relevant predictors for remission. Conclusion The results of our study suggest that migration status has a clinically relevant influence on severity of somatoform and depressive symptoms at admission. Clinical relevance of migration status can also be assumed regarding the remission of depression. Migration status and further factors affecting the effectiveness of the treatment should be analyzed in future research among larger samples with sufficient power to replicate these findings.
CRIS-Team Scopus Importer:2021-10-22

Predictors of cancer patients' utilization of psychooncological support: Examining patient´s attitude and physician´s recommendation - Goerling, Ute; Albus, Christian; Bergelt, Corinna; Erim, Yesim; Faller, Hermann; Geiser, Franziska; Hönig, Klaus; Hornemann, Beate; Maatouk, Imad; Stein, Barbara; Teufel, Martin; Wickert, Martin; et al. (Journal of Cancer Research and Clinical Oncology, 2023)
Purpose: Patients with cancer suffer from a wide range of psychological distress. Nevertheless, in the literature low utilization rates of psychooncological services are reported. Various factors may influence the utilization of professional support during inpatient care. Up to now it is unclear to what extent patients’ attitude towards psychooncological support and physicians’ recommendation for psychooncological care may influence the utilization. Methods: In a multicenter longitudinal observational study in Comprehensive Cancer Centers Germany, 1398 patients with mixed cancer diagnoses were assessed at baseline during their hospital stay with respect to psychooncological distress and the need for and use of psychooncological services. Results: Psychooncological support was used by almost 28.4% of patients up to this time. A positive attitude towards psychooncological support was reported by 41.6%. A recommendation of psychooncological support by a physician was received by 16.2%. These patients reported a significant higher level of distress compared to patients who did not received a recommendation. Multivariable logistic regression detected that the utilization rate was 3.79 times higher among patients with positive attitude towards psychooncological support (OR, 3.79; 95% CI 2.51–5.73, p < 0.001). Utilization was 4.21 times more likely among patients who received a physician´s recommendation (OR, 4.21; 95% CI 2.98–5.95, p < 0.001). Conclusion: The results of the study provide evidence of the relevance of giving more attention to psychooncological distress and attitudes towards psychooncological care. To reduce reservations, patients need low-threshold information about the psychooncological services offered.
CRIS-Team Scopus Importer:2023-11-24
Keywords: Attitude; Cancer; Physician´s recommendation; Psychooncological support; Utilization

Predictors of expressed, felt, and normative needs for informal caregiver counseling: Domestic care for people aged 65+ years - Scheuermann, Julia-Sophia; Grässel, Elmar; Pendergrass, Anna (Zeitschrift für Gerontologie und Geriatrie, 2022)
Background: Informal caregivers (CGs) often fail to recognize or express a need for informal caregiver counseling (ICC) but ICC is an essential but relatively rarely used support service for CGs. Objective: Our aim is to identify predictors of CGs’ need for ICC. Stirling et al.’s need model, which includes three needs (expressed, felt, and normative), serves as a theoretical basis. Material and methods: Analyses are based on cross-sectional data (n = 958) from the “Benefits of being a caregiver” study. Predictors of the need to use ICC were analyzed with binary logistic regression. A sensitivity analysis using multiple linear regression was performed for the metric value of normative needs. Results: We found that 6.8% of CGs currently or have recently used ICC. This expressed need was related to higher education and higher effort in instrumental activities; 24.1% of CGs reported an intention to use ICC in the future. This felt need was related to male gender, lower care level, more problem-focused coping, and a desire for more informal help. Objective need for ICC (normative need), which was related to a higher burden of care, less experienced benefits, and negative relationship quality, was reported by 21.4% of CGs. According to a sensitivity analysis, higher education, a desire for informal help, and living in separate households also predicted a normative need for counseling. Discussion: Current utilization is significantly lower than the subjectively perceived and objectively existing need for ICC. The identified predictors provide initial strategies for motivating more CGs to use ICC.
CRIS-Team Scopus Importer:2022-09-09
Keywords: Home care; Informal caregiver counseling; Informal caregivers; Needs; Utilization

Predictors of falls and hospital admissions in people with cognitive impairment in day-care: role of multimorbidity, polypharmacy, and potentially inappropriate medication - Scheel, Jennifer; Luttenberger, Katharina; Grässel, Elmar; Kratzer, André; Donath, Carolin (BMC Geriatrics, 2022)
Background Multimorbidity, polypharmacy, and potentially inappropriate medication (PIM) pose challenges for the care of people with cognitive impairment. The aim of the present study is to explore whether multimorbidity, polypharmacy, and PIM predict falls and hospital admissions in a sample of people with cognitive impairment in day-care centers in Germany. Methods We used data from the German day-care study (multicenter longitudinal study, n = 433). Multimorbidity was defined as >= 2 chronic diseases. Polypharmacy was defined as prescriptions to >= 5 drugs. Potentially inappropriate medication was defined as scoring on the PRISCUS list. Binary logistic regression analyses were computed to determine whether multimorbidity, polypharmacy, and potentially inappropriate medication at t0 predicted falls and hospital admissions as outcomes at t1 (six months later). Results The rate of multimorbidity and polypharmacy was 87.8% and 60.3%, respectively. 15.9% of the people with cognitive impairment received PIM / PRISCUS-listed drugs, 43.6% ACB-listed drugs, and 52.7% CNS depressant drugs. Falls and hospital admissions during follow-up were prevalent in 19.4% and 24.7% of the people with cognitive impairment. Both were significantly predicted by the total number of drugs (falls: OR = 1.152, p = 0.001, overall model: p < 0.001; hospital admissions: OR = 1.103, p = 0.020, overall model: p = 0.001), even if regression analyses were controlled for the number of comorbidities. Conclusions Polypharmacy and potentially inappropriate medication are highly prevalent in people with cognitive impairment in German day-care centers. The number of drugs and appropriateness of medication seem to be crucial for the risk of falls and hospital admissions. Polypharmacy and PIM should be critically reviewed by healthcare providers and avoided as much as and whenever possible.
CRIS-Team WoS Importer:2022-08-26

Predictors of institutionalization in users of day care facilities with mild cognitive impairment to moderate dementia - Spiegl, Klara; Luttenberger, Katharina; Grässel, Elmar; Becker, Linda; Scheel, Jennifer; Pendergrass, Anna (BMC Health Services Research, 2021)
Background: Most people with dementia wish to remain at home for as long as possible. Therefore, it is important to know the predictors of institutionalization, especially those that can be influenced. The aim of the present study is to identify predictors of the institutionalization of people with mild cognitive impairment (MCI) to moderate dementia who attend day care facilities (DCFs) throughout Germany.
CRIS-Team WoS Importer:2021-10-01

Predictors of intensity of use of adult day care centers in people with cognitive impairment - Wasic, Catharina; Grässel, Elmar; Luttenberger, Katharina; Donath, Carolin (Zeitschrift für Gerontologie und Geriatrie, 2021)
Background Adult day care is an established concept in Germany for people with cognitive impairment; however, only a small fraction of people in need for care actually use adult day care. Studies so far highlighted some predictors for the use of adult day care; however, it remains unclear which factors are associated with the intensity of use. Objective To identify relevant predictors for the intensity of use of adult day care using the Andersen healthcare utilization model. Material and methods Data used were obtained within the project dementia in day care with psychosocial MAKS interventions (DeTaMAKS), which studied adult day care users with cognitive impairments and their family caregivers. A logistic regression was performed to predict frequent or low use of adult day care. Results The following factors were significantly associated with higher intensity of use: civil status of adult care user being widowed or single, higher educational level of caregiver, higher care level, longer duration of adult day care use and more mental and behavioral symptoms of the adult day care user. The sensitivity analysis for cohabiting dyads additionally showed a higher intensity of use with a lower age of the caregiver and shorter distance between place of residence and adult day care but not with respect to educational level of the caregiver and mental and behavioral symptoms of the user. Conclusion The results show a need for adult day care, which increases with caregivers being employed and users living outside of permanent relationships. A short distance to the adult care center as well as flexible care options may increase the frequency of use.
CRIS-Team WoS Importer:2021-10-08

Predictors of Psychological Stress in Breast Cancer Patients - What Should Physicians and Nursing Staff Pay Attention to in an Oncological Setting? - Erim, Yesim; Beckmann, M.; Hoffmann, O.; Senf, W.; Kimmig, Rainer; Wimberger, P. (Geburtshilfe und Frauenheilkunde, 2011)
Keywords: breast cancer; psychooncology; anxiety; depression; need for psychosocial intervention

Predictors of the personal benefits and positive aspects of informal caregiving - Pendergrass, Anna; Mittelman, Mary; Grässel, Elmar; Özbe, Dominik; Karg, Nina (Aging & Mental Health, 2019)
Objective: We investigated a) the number of reported benefits in an informal caregiving situation and b) the factors that predict the caregiver's (CG's) experience of benefits. Method: In this cross-sectional study, we computed univariate analyses and a multiple regression analysis using a benefit score as the dependent variable. Participants were 734 informal CGs who provide care for a person with chronic care needs in Germany. We examined the CG's self-reported physical complaints (GBB-24), subjective burden (CSI), depressive symptoms (PHQ-9), quality of life (CarerQoL), and benefits (BIZA-D). Results: Most of the CGs (87.1%) experienced benefits in at least one field. A higher experience of benefits was significantly associated with: more depressive symptoms (r = 0.10), higher burden (r = 0.17), longer duration of care (r = 0.07), longer daily care time (r = 0.21), more physical complaints (r = 0.15), and a good quality of the relationship between CG and CR (eta = 0.13). In the multivariate regression analysis, a good relationship between the CG and CR (beta = .157, P < .001), an increased amount of care time (beta = .188, P < .001), and a higher level of burden (beta = .167, P < .001) were associated with greater CG's benefits. Conclusion: CG benefits are a very important, often experienced, but less-explored construct in caregiving research. Benefits do not seem to be on the opposite end of the same continuum as negative aspects of caregiving. Benefits appear to be a nearly distinct dimension in informal care settings.
CRIS-Team WoS Importer:2019-10-04

Predictors of the Quality of Life in oncologic Patients with special Consideration of different Time Intervals since the Diagnosis Condition - Morawa, Eva; Aderhold, Caroline; Paslakis, Georgios; Erim, Yesim (2017)
EVALuna2:214439

Prenatal alcohol exposure and the facial phenotype in adolescents: A study based on meconium ethyl glucuronide - Maschke, Janina; Roetner, Jakob; Goecke, Tamme; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Lenz, Bernd; Kornhuber, Johannes; Eichler, Anna (Brain Sciences, 2021)
Here, we explore the effects of prenatal alcohol exposure (PAE) in adolescence. We investigated associations between meconium ethyl glucoronide (EtG) and facial malformation. For 29 children (66/63 male/female; M = 13.3, SD = 0.32, 12–14 years), PAE was implemented by newborn meconium EtG and maternal self-reports during the third trimester. Cognitive development was operationalized by standardized scores (WISC V). The EtG cut-off values were set at ≥10 ng/g (n = 32, 24.8% EtG10+) and ≥112 ng/g (n = 20, 15.5% EtG112+). The craniofacial shape was measured using FAS Facial Photographic Analysis Software. EtG10+− and EtG112+-affected children exhibited a shorter palpebral fissure length (p = 0.031/p = 0.055). Lip circularity was smaller in EtG112+-affected children (p = 0.026). Maternal self-reports were not associated (p > 0.164). Lip circularity correlated with fluid reasoning (EtG10+ p = 0.031; EtG112+ p = 0.298) and working memory (EtG10+ p = 0.084; EtG112+ p = 0.144). The present study demonstrates visible effects of the facial phenotype in exposed adolescents. Facial malformation was associated with a child’s cognitive performance in the alcohol-exposed group. The EtG biomarker was a better predictor than maternal self-reports.
CRIS-Team Scopus Importer:2021-03-19
Keywords: Alcohol; Biomarker; Craniofacial shape; Ethyl glucuronide (EtG); Facial malformations; Inner canthal distance; Intrauterine alcohol exposure; Lip circularity; Meconium; Palpebral fissure length

Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children - Frey, Silke; Eichler, Anna; Stonawski, Valeska; Kriebel, Jennifer; Wahl, Simone; Gallati, Sabina; Goecke, Tamme W.; Fasching, Peter A.; Beckmann, Matthias W.; Kratz, Oliver; Moll, Gunther; Heinrich, Hartmut; et al. (Frontiers in Behavioral Neuroscience, 2018)
Prenatal alcohol exposure (PAE) is known to elicit a broad range of systemic effects, including neurophysiological alterations that result in adverse behavioral and cognitive outcomes. However, molecular pathways underlying these long-term intrauterine effects remain to be investigated. Here, we tested a hypothesis that PAE may lead to epigenetic alterations to the DNA resulting in attentional and cognitive alterations of the children. We report the results of the study that included 156 primary school children of the Franconian Cognition and Emotion Studies (FRANCES) cohort which were tested for an objective marker of PAE, ethyl glucuronide (EtG) in meconium at birth. Thirty-two newborns were found to be exposed to alcohol with EtG values above 30 ng/g (EtG+). Previously we described PAE being associated with lower IQ and smaller amplitude of the event-related potential component P3 in go trials (Go-P3), which indicates a reduced capacity of attentional resources. Whole-genome methylation analysis of the buccal cell DNA revealed 193 differentially methylated genes in children with positive meconium EtG, that were clustered into groups involved in epigenetic modifications, neurodegeneration, neurodevelopment, axon guidance and neuronal excitability. Furthermore, we detected mediation effects of the methylation changes in DPP10 and SLC16A9 genes on the EtG related cognitive and attention-related deficits. Our results suggest that system-wide epigenetic changes are involved in long-term effects of PAE. In particular, we show an epigenetic mediation of PAE effects on cognition and attention-related processes.
EVALuna2:36368

Prenatal and adult androgen activities in alcohol dependence - Lenz, Bernd; Mühle, Christiane; Braun, B.; Weinland, C.; Bouna-Pyrrou, Polyxeni; Behrens, Juliane; Kubis, S.; Mikolaiczik, Katrin; Muschler, M. -R.; Saigali, Sarah; Sibach, M.; Tanovska, P.; et al. (Acta Psychiatrica Scandinavica, 2017)
OBJECTIVE: Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. METHOD: We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). RESULTS: The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). CONCLUSION: Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.
EVALuna2:33408

Prenatal Androgen Influence on Addictive Behaviour in Adolescence Vorgeburtlicher Androgen- einfluss auf süchtiges Verhalten in der Adoleszenz - Lenz, Bernd; Eichler, Anna; Buchholz, Verena Nadine; Fasching, Peter; Kornhuber, Johannes (Sucht, 2021)
Background: Men consume alcohol, tobacco, and illicit drugs more often than women, and they are more prone to pathological gambling and addictive internet gaming. These sex differences are already found during adolescence. The consumption patterns are related to externalizing behavior. In addition to social influences, biological factors play a central role in the development of these differences between men and women. Prenatal exposure to androgens and estrogens shape the brain development with functional and structural effects that persist into adulthood. Intrauterine sex hormone exposure is related to maternal risk factors such as stress and substance use. Aim: In this narrative review, we discuss the potential impact of prenatal androgen exposure in the womb on the development of addictive behaviors and self-regulation in later life. In recent years, this issue has been addressed by animal experiments with direct modulation of prenatal androgenization and clinical association studies based on biomarkers such as the second-to-fourth finger lengths ratio (2D:4D). Results: The available body of literature suggests that reinforced brain androgenization during the intrauterine development increases the risk for addictive behaviors and deficits in self-regulation capacity in later life. Finally, we also discuss prevention strategies during pregnancy targeting this model and refer to the Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention study. This investigation is a subproject of the IMAC-Mind research collaborative project to improve mental health and reduce addiction risk in childhood and adolescence through mindfulness.
CRIS-Team Scopus Importer:2021-12-24
Keywords: addiction; adolescence; dependence; prenatal development; testosterone

Prenatal androgen receptor activation determines adult alcohol and water drinking in a sex-specific way - Huber, Sabine; Zoicas, Iulia; Reichel, Martin; Mühle, Christiane; Büttner, Christian; Ekici, Arif Bülent; Eulenburg, Volker; Lenz, Bernd; Kornhuber, Johannes; Müller, Christian P. (Addiction Biology, 2017)
Alcohol use disorders are major psychiatric disorders. Correlational studies in humans suggested organizational hormonal effects during embryonic development as a risk factor for adult alcohol dependence. Permanent changes can be induced by the activity of sex hormones, like testosterone. Here, we demonstrate a relationship between prenatal androgen receptor (AR)-activation and adult alcohol as well as water drinking in mice in a sex-dependent fashion. Prenatal AR inhibition using the antagonist flutamide decreased adult male alcohol consumption. In contrast, prenatal AR activation by dihydrotestosterone (DHT) led to an increase in adult alcohol consumption in females. These effects were different in adult water drinking, flutamide increased water consumption in females and DHT increased water consumption in males. Prenatal flutamide reduced locomotion and anxiety in adult males but was ineffective in females. We found that prenatal AR activation controls adult levels of monoaminergic modulatory transmitters in the brain and blood hormone levels in a sex-specific way. RNA-Seq analysis confirmed a prenatal AR mediated control of adult expression of alcohol drinking-related genes like Bdnf and Per2. These findings demonstrate that prenatal androgen activity is a risk factor for the establishment of alcohol consumption in adults by its organizational effects.
EVALuna2:4035

Prenatal androgen-receptor activity has organizational morphological effects in mice - Huber, Sabine; Lenz, Bernd; Kornhuber, Johannes; Müller, Christian P. (PLoS ONE, 2017)
Prenatal sex hormones exert organizational effects. It has been suggested that prenatal sex hormones affect adult morphological parameters, such as the finger length. Especially the second-to-fourth finger length (2D:4D) ratio has been implicated to be modified when exposed to higher androgen levels in utero. Here we show in a mouse model that experimental manipulation of the prenatal androgen level, by blocking the androgen receptor with flutamide or activating the androgen receptor with dihydrotestosterone (DHT), leads to changes in the length of the fingers of all paws in males and females. In addition to that, also total paw length and the 2D:4D ratio was affected. In males treated with DHT, the 2D:4D ratio was increased, while flutamide-treatment in females led to a reduced 2D:4D ratio. We also measured other parameters, such as head size, body length and tail length and demonstrate that body morphology is affected by prenatal androgen exposure with more prominent effects in females. Another factor that is thought to be influenced by early androgens is handedness. We tested mice for handedness, but did not find a significant effect of the prenatal treatment. These findings demonstrate that prenatal androgen activity is involved in the development of body morphology and might be a useful marker for prenatal androgen exposure.
EVALuna2:33379

Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5 - Plank, Anne-Christine; Frey, Stefan; Basedow, Lukas Andreas; Solati, Jalal; Canneva, Fabio; von Hörsten, Stephan; Kratz, Oliver; Moll, Gunther; Golub, Yulia (Translational Psychiatry, 2021)
In our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.
CRIS-Team Scopus Importer:2021-04-09

Prenatal testosterone activity determines adult alcohol drinking and morphology in mice - Huber, Sabine; Lenz, Bernd; Kornhuber, Johannes; Müller, Christian P. (2016)
EVALuna2:33260

Presynaptic vesicular accumulation is required for antipsychotic efficacy in psychotic-like rats - Uzuneser, Taygun; Weiss, Eva Maria; Dahlmanns, Jana; Kalinichenko, Liubov; Amato, Davide; Kornhuber, Johannes; Alzheimer, Christian; Hellmann, Jan; Kaindl, Jonas; Hübner, Harald; Löber, Stefan; Gmeiner, Peter; et al. (Journal of Psychopharmacology, 2021)
Background: The therapeutic effects of antipsychotic drugs (APDs) are mainly attributed to their postsynaptic inhibitory functions on the dopamine D2 receptor, which, however, cannot explain the delayed onset of full therapeutic efficacy. It was previously shown that APDs accumulate in presynaptic vesicles during chronic treatment and are released like neurotransmitters in an activity-dependent manner triggering an auto-inhibitory feedback mechanism. Although closely mirroring therapeutic action onset, the functional consequence of the APD accumulation process remained unclear. Aims: Here we tested whether the accumulation of the APD haloperidol (HAL) is required for full therapeutic action in psychotic-like rats. Methods: We designed a HAL analog compound (HAL-F), which lacks the accumulation property of HAL, but retains its postsynaptic inhibitory action on dopamine D2 receptors. Results/outcomes: By perfusing LysoTracker fluorophore-stained cultured hippocampal neurons, we confirmed the accumulation of HAL and the non-accumulation of HAL-F. In an amphetamine hypersensitization psychosis-like model in rats, we found that subchronic intracerebroventricularly delivered HAL (0.1 mg/kg/day), but not HAL-F (0.3–1.5 mg/kg/day), attenuates psychotic-like behavior in rats. Conclusions/interpretation: These findings suggest the presynaptic accumulation of HAL may serve as an essential prerequisite for its full antipsychotic action and may explain the time course of APD action. Targeting accumulation properties of APDs may, thus, become a new strategy to improve APD action.
CRIS-Team Scopus Importer:2020-12-11
Keywords: behavior; Haloperidol; presynaptic accumulation; schizophrenia

Prevalence and Modifiable Determinants of Non-Adherence in Adult Kidney Transplant Recipients in a German Sample - Reber, Sandra Therese; Morawa, Eva; Stößel, Lisa; Jank, Sabine; Vitinius, Frank; Eckardt, Kai-Uwe; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2016)
EVALuna2:3905

Prevalence, Comorbidity and Severity of Psychosomatic Disorders in Outpatients with Turkish Migration Background - Erim, Yesim; Morawa, Eva; Ozdemir, Dilsad Foto; Senf, Wolfgang (Psychotherapie Psychosomatik Medizinische Psychologie, 2011)
Keywords: immigrants; mental disorders; prevalence; comorbidity; SCID