Prevalence of COVID-19 and Psychotropic Drug Treatment in Psychiatric In-patients in Germany in 2020: Results from a Nationwide Pilot Survey - Mueller, Juliane K.; Ahrens, Kira F.; Bauer, Michael; Baune, Bernhard T.; Borgwardt, Stefan; Deckert, Jürgen; Domschke, Katharina; Ellwanger, Regina; Fallgatter, Andreas; Frodl, Thomas; Gallinat, Jürgen; Gottschalk, René; et al. (Pharmacopsychiatry, 2023)
Introduction In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of COVID-19 and an increased mortality have been described. Conversely, observations of lower COVID-19 incidences in psychiatric in-patients suggested protective effects of psychiatric treatment and/or psychotropic drugs against COVID-19. Methods A retrospective multi-center study was conducted in 24 German psychiatric university hospitals. Between April and December 2020 (the first and partly second wave of COVID-19), the effects of COVID-19 were assessed on psychiatric in-patient care, the incidence and course of a SARS-CoV-2 infection, and treatment with psychotropic drugs. Results Patients (n=36,322) were admitted to the hospitals. Mandatory SARS-CoV-2 tests before/during admission were reported by 23 hospitals (95.8%), while 18 (75%) conducted regular testing during the hospital stay. Two hundred thirty-two (0.6%) patients were tested SARS-CoV-2-positive. Thirty-seven (16%) patients were receiving medical treatment for COVID-19 at the psychiatric hospital, ten (4.3%) were transferred to an intermediate/intensive care unit, and three (1.3%) died. The most common prescription for SARS-CoV-2-positive patients was for second-generation antipsychotics (n=79, 28.2%) and antidepressants (SSRIs (n=38, 13.5%), mirtazapine (n=36, 12.9%) and SNRIs (n=29, 10.4%)). Discussion Contrary to previous studies, our results showed a low number of infections and mortality in SARS-CoV-2-positive psychiatric patients. Several preventive measures seem effective to protect this vulnerable group. Our observations are compatible with the hypothesis of a protective effect of psychotropic drugs against COVID-19 as the overall mortality and need for specific medical treatment was low.
CRIS-Team Scopus Importer:2023-11-24
Keywords: COVID-19; psychiatry; psychotropic drugs; SARS-CoV-2

Prevalence of Mental Distress Among Syrian Refugees With Residence Permission in Germany: A Registry-Based Study. - Georgiadou, Ekaterini; Zbidat, Ali; Schmitt, Gregor M.; Erim, Yesim (Frontiers in Psychiatry, 2018)
Background: High rates of prevalence of mental distress among the Syrian refugee population have been repeatedly confirmed. However, little is known about the influence of length of stay, living conditions, and residence permission in the host country or about the duration of the escape journey and travel conditions on mental health in this refugee population. This study examines the mental health of Syrian refugees, taking into account the circumstances in their country of origin and host country, as well as their escape conditions. Methods: This investigation formed part of a registry-based study. A sample of 518 adult Syrian refugees in Erlangen, Germany, who have residence permission was identified. The response rate was 38.6%; a total of 200 Syrian refugees thus participated in the study. The respondents were investigated for post-traumatic stress disorder (ETI), depression (PHQ-9), generalized anxiety (GAD-7) and post-migration variables. Results: The prevalence of participants who had personally experienced and/or witnessed traumatic events was 75.3%. Symptoms of PTSD were found in 11.4% of the participants. Moderate to severe depression was confirmed in 14.5% and moderate to severe generalized anxiety in 13.5% of the sample. The criteria for at least one diagnosis were met by 30.5% of the participants. More severe PTSD symptoms were associated with older age, shorter validity of the residence permit, larger number of traumatic events (TEs) and higher generalized anxiety symptoms. Depression symptoms were associated with younger age, shorter duration of escape journey, larger number of TEs and higher generalized anxiety symptoms. Generalized anxiety symptoms correlated with female gender, PTSD, and depression symptoms. Conclusions: These findings suggest that Syrian refugees in Germany are a vulnerable population, especially if they have experienced and/or witnessed multiple traumatic events. However, post-migration conditions and positive future prospects in the host country can be protective factors for this population.
EVALuna2:214429

Prevalence of Mental Distress Among Syrian Refugees With Residence Permission in Germany: A Registry-Based Study - Georgiadou, Ekaterini; Zbidat, Ali; Schmitt, Gregor Martin; Erim, Yesim (Frontiers in Psychiatry, 2018)

Prevalence of mental distress in Syrian refugees with residence permission in Germany - Erim, Yesim; Zbidat, A.; Schmitt, G. M.; Georgiadou, Ekaterini (2018)
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Prevalence of the apolipoprotein E ?4 allele in amyloid ? positive subjects across the spectrum of Alzheimer's disease - Mattsson, Niklas; Groot, Colin; Jansen, Willemijn J.; Landau, Susan M.; Villemagne, Victor L.; Engelborghs, Sebastiaan; Mintun, Mark M.; Lleo, Alberto; Molinuevo, Jose Luis; Jagust, William J.; Frisoni, Giovanni B.; Ivanoiu, Adrian; et al. (Alzheimers & Dementia, 2018)
Apolipoprotein E (APOE) ?4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid ? (A?) pathology.We included 3451 A?+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ?4 prevalence in relation to age, sex, education, and geographical location.The APOE ?4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A?+ cognitively normal and A?+ mild cognitive impairment (P < .05) but not in A?+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education.The APOE ?4 prevalence in AD was higher than that in previous studies, which did not require presence of A? pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
EVALuna2:92001

Processing of food stimuli in anorexia nervosa: An ERP-study comparing adolescents and adults - Stonawski, Valeska; Mai-Lippold, Sandra A.; Graap, Holmer; Moll, Gunther; Kratz, Oliver; Van Doren, Jessica; Horndasch, Stefanie (European Eating Disorders Review, 2023)
Background: Anorexia nervosa (AN) is associated with altered processing of disorder-relevant stimuli. Event-related potentials (ERP) – such as the Late Positive Potential (LPP) – give information about the underlying mechanisms of central nervous stimulus processing. Methods: Patients with AN (22 adolescents, 23 adults) and healthy controls (HCs; 17 adolescents, 24 adults) were included. Neutral, low, and high calorie food-images were rated for valence and arousal; EEG activity was recorded and LPPs (early: 350–700 ms; late: 800–1200 ms) were extracted. Effects of patient status, age group, and stimulus category were analyzed via mixed 2 × 2 × 3-AN(C)OVAs. Results: Patients with AN rated high calorie stimuli lower in valence and higher in arousal than HCs. Controlling for hunger, food stimuli elicited higher early LPPs than neutral ones in patients and HCs. For the late LPP, patients with AN showed larger amplitudes. Conclusion: Results suggest a highly automatic attentional bias towards low-calorie foods. Patients with AN seem to have more intense cognitive processing independent of stimulus material. More research is needed to validate and clarify differences between early and late LPP measures as well as the operationalization and relevance of hunger status.
CRIS-Team Scopus Importer:2023-10-27
Keywords: adulthood; anorexia nervosa; childhood; food; LPP

Professional and volunteer refugee aid workers–depressive symptoms and their predictors, experienced traumatic events, ptsd, burdens, engagement motivators and support needs - Borho, Andrea; Georgiadou, Ekaterini; Grimm, Theresa; Morawa, Eva; Silbermann, Andrea; Nißlbeck, Winfried; Erim, Yesim (International Journal of Environmental Research and Public Health, 2019)
In 2016, the Department of Psychosomatic Medicine and Psychotherapy of the University Hospital of Erlangen started conducting training for professional and voluntary aid workers. In total, 149 aid workers took part in the training courses, of which 135 completed the corresponding questionnaires. Engagement motivators, perceived distress in refugee work and training needs were examined. Moreover, depressive symptoms, the prevalence of traumatic experiences and symptoms of posttraumatic stress disorder were explored. Participants named helping others as the highest motivating factor for their work with refugees and communication problems as the main burden. Thirteen aid workers (10.1%) showed clinically relevant depressive symptoms. In total, 91.4% of refugee aid workers had experienced at least one traumatic event personally or as a witness but only three (3.6%) fulfilled the psychometric requirements of a PTSD diagnosis. These three participants all belonged to the professional aid workers (6.3%). More severe symptoms of depression were significantly associated with female gender (β = 0.315, p = 0.001), higher perceived burdens of refugee work (β = 0.294, p = 0.002), and a larger number of experienced traumatic events (β = 0.357, p < 0.001). According to our results, we recommend psychological trainings and regular screenings for psychological stress in order to counteract possible mental illnesses.
CRIS-Team Scopus Importer:2019-11-29
Keywords: Burdens; Depression; Engagement motivators; Germany; PTSD; Refugee aid workers; Support needs; Trainings; Traumatic experiences

Progesterone serum levels correlate negatively with craving in female postmenopausal in-patients with alcohol use disorder: A sex- and menopausal status-separated study - Weinland, Christian; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2021)
Objective: Alcohol use disorder (AUD) shows a high prevalence and often takes a severe and chronic course. However, the underlying mechanisms still need to be better understood. There is increasing evidence for a role of sex hormones in AUD and for the importance of sex-separated concepts in addiction research. Nevertheless, only few data give insight into how progesterone is involved in AUD. Method: Serum progesterone levels were measured at baseline (during early abstinence) in 186 in-patients with AUD (19% premenopausal females, 20% postmenopausal females, 61% males) and at median 5 days later. They were compared with those of 233 healthy control subjects (24% premenopausal females, 19% postmenopausal females, 57% males). We quantified craving with the Obsessive Compulsive Drinking Scale (OCDS) and visual analogue scales (VAS). Alcohol-related hospital readmissions within a 24-month period following initial in-patient treatment were recorded. We conducted analyses separately for sex and for menopausal status in female participants. Results: Postmenopausal females with AUD reported higher craving than premenopausal females. In postmenopausal females, higher baseline progesterone levels correlated with lower OCDS total craving and VAS craving, i.e., lower state craving and lower average, maximum, and less frequent craving during withdrawal. In males with AUD, progesterone levels at baseline tended to be higher than in controls and declined to follow-up. Alcohol-related readmissions were not significantly associated with serum progesterone levels. Conclusion: We provide first evidence that progesterone levels correlate with craving in females with AUD.
CRIS-Team Scopus Importer:2021-04-23
Keywords: AUD; Craving; Progesterone; Sex hormones

Prognostic influence of witness/victim experiences and PTSD-specific symptoms on working and educational capacity: a comparison between two groups of individuals post-trauma - Mueller, Helge H.; Möller, Sebastian; Hilger, York; Sperling, Wolfgang (Annals of General Psychiatry, 2015)
Trauma exposure depends of the type of trauma and can result in the development of posttraumatic stress disorder (PTSD). The type of traumatization (such as Holocaust experiences and other sources of trauma) and specific symptoms of PTSD have influences on the outcome, and specific symptoms of PTSD influence personal and professional outcomes. Another factor is the role of the victim in their traumatization. Some patients are actively traumatized through being victims of torture, while others are passively traumatized by witnessing the traumatization of others.We compared two groups of victim/witness trauma sufferers (PTSD vs. Holocaust-experience PTSD (HE-PTSD)) with regard to PTSD symptoms, educational and working capacity, and functional outcome parameters.HE-PTSD survivors with victim/witness trauma experience showed substantially more specific PTSD symptoms and higher symptom-specific intensities but had high social function and education levels. The intensity and type of intrusive memories and sociodemographic factors do not seem to have a prognostic influence on working or educational outcomes.Identifying the combined victim/witness experience seems to play an important prognostic role in the assessment of PTSD victims. Further studies should consider these findings within other specific traumatization groups.
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Prognostic value of cta-derived left ventricular mass in neonates with congenital heart disease - Ellmann, Stephan; Nickel, Julie-Marie; Heiß, Rafael; El Amrani, Nouhayla; Wüst, Wolfgang; Rompel, Oliver; Rueffer, Andre; Cesnjevar, Robert; Dittrich, Sven; Uder, Michael; May, Matthias (Diagnostics, 2021)
For therapeutic decisions regarding uni-or biventricular surgical repair in congenital heart disease (CHD), left ventricular mass (LVM) is an important factor. The aim of this retrospective study was to determine the LVM of infants with CHD in thoracic computed tomography angiographies (CTAs) and to evaluate its usefulness as a prognostic parameter, with special attention paid to hypoplastic left heart (HLH) patients. Manual segmentation of the left ventricular endo-and epicardial volumes was performed in CTAs of 132 infants. LVMs were determined from these volumes and normalized to body surface area. LVMs of patients with different types of CHD were compared to each other using analyses of variances (ANOVA). An LVM cutoff for discrimination between uni-and biventricular repair was determined using receiver operating characteristics. Survival rates were calculated using Kaplan–Meier statistics. Patients with a clinical diagnosis of an HLH had significantly lower mean LVM (21.88 g/m2) compared to patients without applicable disease (50.22 g/m2; p < 0.0001) and compared to other CHDs, including persistent truncus arteriosus, left ventricular outflow tract obstruction, transposition of the great arteries, pulmonary artery stenosis or atresia, and double-outlet right ventricle (all, p < 0.05). The LVM cutoff for uni-vs. biventricular surgery was 33.9 g/m2 (sensitivity: 82.3%; specificity: 73.7%; PPV: 94.9%). In a subanalysis of HLH patients, a sensitivity of 50.0%, specificity of 100%, PPV of 100%, and NPV of 83.3% was determined. Patient survival was not significantly different between the surgical approaches or between patients with LVM above or below the cutoff. LVM can be measured in chest CTA of newborns with CHD and can be used as a prognostic factor.
CRIS-Team Scopus Importer:2021-07-30
Keywords: Cardiac computed tomography; Computed tomography angiography; Congenital heart disease; Heart imaging; Heart surgery; Hypoplastic left heart

Prominent Non-Memory Deficits in Alzheimer's Disease Are Associated with Faster Disease Progression - Scheltens, Nienke M. E.; Tijms, Betty M.; Heymans, Martijn W.; Rabinovici, Gil D.; Cohn-Sheehy, Brendan; Miller, Bruce L.; Kramer, Joel H.; Wolfsgruber, Steffen; Wagner, Michael; Kornhuber, Johannes; Peters, Oliver; Scheltens, Philip; et al. (Journal of Alzheimer's Disease, 2018)
BACKGROUND: Alzheimer's disease (AD) is a heterogeneous disorder. OBJECTIVE: To investigate whether cognitive AD subtypes are associated with different rates of disease progression. METHODS: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses. RESULTS: Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; pinteraction<0.001; CDR sob 1.3±0.1; pinteraction<0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00-1.85, p = 0.05). CONCLUSIONS: AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment.
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Prospective, randomized, double-blind, placebo-controlled phase IIa clinical trial on the effects of an estrogen-progestin combination as add-on to inpatient psychotherapy in adult female patients suffering from anorexia nervosa - Paslakis, Georgios; Maas, Stefanie; Gebhardt, Bernd; Mayr, Andreas; Rauh, Manfred; Erim, Yesim (BMC Psychiatry, 2018)

Prospective single-centre clinical observational study on electronically monitored medication non-adherence, its psychosocial risk factors and lifestyle behaviours after heart transplantation: A study protocol - Lieb, Marietta; Weyand, Michael; Seidl, Margot; Erim, Yesim (BMJ Open, 2020)
Introduction In heart transplant recipients (HTRs), non-adherence (NA) to immunosuppressive (IS) medication and to recommended lifestyle behaviours are a common phenomenon and associated with higher risk of allograft rejection, organ loss and mortality. Risk factors for NA are highly diverse and still insufficiently researched. Precise measures of NA and an accurate understanding of its aetiology are of undisputable importance to detect patients at risk and intervene accordingly. The aim of this study is to assess the accuracy and concordance of different measures for NA as well as to determine potential risk factors. Methods and analysis This is a single-centre prospective observational trial. HTRs who are at least aged 18 are no less than 6 months post-transplant and receive tacrolimus (Prograf or Advagraf), cyclosporine (Sandimmun) or everolimus (Certican) as their prescribed IS medication are eligible for participation. We only include patients during the phase of medication implementation. At study enrolment, we assess depression, health-related quality of life, self-efficacy, social support, attachment, experiences and attitudes towards IS medication, emotional responses after transplantation, satisfaction with information about IS medication and perceptions and beliefs about medications. We further ask patients to rate their lifestyle behaviours concerning alcohol, smoking, diet, physical activity, sun protection and appointment keeping via questionnaires. Three different measurement methods for NA are applied at T0: self-reports, physician's estimates and IS trough levels. NA is monitored prospectively using an electronic multicompartment pillbox (MEMS, VAICA) over a 3-month period. Meanwhile, participants receive phone calls every second week to obtain additional self-reports, resulting in a total of seven measurement points. Ethics and dissemination The study was approved by the Clinical Ethics Committee of the University Hospital Erlangen (Friedrich-Alexander-University, Erlangen-Nürnberg). Written informed consent is attained from all participants. The results of this study will be published in peer-reviewed journals and presented at conferences. Trial registration number DRKS00020496.
CRIS-Team Scopus Importer:2020-10-23
Keywords: cardiology; statistics & research methods; transplant medicine

Protective factors of depressive symptoms in adult cancer patients: The role of sense of coherence and posttraumatic growth in different time spans since diagnosis - Aderhold, Caroline; Morawa, Eva; Paslakis, Georgios; Erim, Yesim (Journal of Psychosocial Oncology, 2019)
Purpose: The purpose of this study was to investigate the impact of posttraumatic growth (PTG) and sense of coherence (SOC) as protective factors on depressive symptoms at different time spans after cancer diagnosis. Design: In a cross-sectional study, adult cancer patients were recruited from the tumor clinics of the University Hospital in Erlangen (Germany) and from peer-support groups for cancer survivors. Sample: Participants included 157 adult patients with primary cancer or in remission (53.5% female; mean age: 58.0 ± 14.1 years; mean time since diagnosis: 46.7 ± 72.8 months) with various forms of cancer. Methods: Multiple linear regression analyses were conducted. The patients were divided into two groups (≤1 year and >1 year since diagnosis) to test the impact of PTG and SOC on depressive symptoms at different time intervals after diagnosis. The Posttraumatic Growth Inventory (PTGI), Sense of Coherence Scale (SOC-13), and Hospital Anxiety and Depression Scale (HADS) were applied. Findings: After controlling for major demographic and clinical variables, SOC (β = –.489, p <.001) was found to be the only significant predictor for depressive symptoms ≤ 1 year after diagnosis; >1 year after diagnosis, SOC (β = –.571, p <.001), PTG (β = –.318, p =.002), and metastatic cancer (β =.231, p =.023) were significant predictors of depressive symptoms (high levels of SOC as well as PTG, and having no metastatic cancer were associated with low manifestations of depressive symptoms). Conclusions: These findings suggest that SOC may be a protective factor against depressive symptoms in both the short as well as in the long term after cancer diagnosis, but PTG only in the long term. Implications for psychosocial providers or policy: To prevent the development of depressive symptoms in cancer patients, individuals with a low SOC should be detected and should receive psychological assistance.
CRIS-Team Scopus Importer:2019-07-16
Keywords: cancer; depression; posttraumatic growth; sense of coherence

Proteomic analysis reveals brain Rab35 as a potential biomarker of mitragynine withdrawal in rats - Hassan, Rahimah; Othman, Nurulhasanah; Mansor, Sharif M.; Müller, Christian P.; Hassan, Zurina (Brain Research Bulletin, 2021)
Mitragyna speciosa, also known as kratom, has been used for mitigating the severity of opioid withdrawal in humans. Its main indole alkaloid, mitragynine, has been considered as a pharmacotherapy for pain conditions and opioid replacement therapy. However, at high doses, chronic mitragynine may also have an addiction potential. The effects of chronic action of mitragynine in the brain are still unknown. The present study developed a mitragynine withdrawal model in rats and used it for a proteomic analysis of mitragynine withdrawal effects. Mitragynine (30 mg/kg, i.p.) was administered daily over a period of 14 days and then withdrawn. A proteomic analysis revealed that from a total of 1524 proteins identified, 31 proteins were upregulated, and 3 proteins were downregulated in the mitragynine withdrawal model. The Rab35 protein expression increased most profoundly in the mitragynine withdrawal group as compared to vehicle group. Therefore, it is proposed that Rab35 in the brain might be considered as a potential biomarker during mitragynine withdrawal and might be valuable target protein in developing new pharmacotherapies in the future.
CRIS-Team Scopus Importer:2021-05-14
Keywords: Kratom; Mitragynine; Protein expression; Proteomic; Withdrawal model

Psychiatric Therapy in the Native Language - Erim, Yesim; Koch, Eckhardt (Psychiatrische Praxis, 2011)

Psychoeducational intervention and problem-solving training for relapse prevention and stabilization in alcoholic patients prior to liver transplantation - Erim, Yesim; et al. (Psychotherapie Psychosomatik Medizinische Psychologie, 2004)

Psychoedukation Angst bei stationären Patienten - Evaluation des kognitiv-verhaltenstherapeutischen Gruppenprogramms „PAsta" - Summ, Elisabeth; Frieling, Helge; Gruß, Barbara; Stemmler, Mark; Bleich, Stefan; Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2009)
Hintergrund: Ziel der vorliegenden Studie war es, ein psychoedukatives Gruppenprogramm für stationär behandelte Patienten mit heterogenen Angststörungen zu entwickeln und zu evaluieren. Methode: 28 stationär behandelte Patienten nahmen zusätzlich zur psychiatrischen Standardtherapie an psychoedukativen Gruppensitzungen teil. Die Ergebnisse dieser Gruppe wurden mit 13 Patienten, die nur die Standardtherapie erhielten (Kontrolle) im Prä-Post-Design bezüglich Krankheitswissen, psychischer Gesundheit und Selbstwirksamkeit verglichen. Ergebnisse: Die Psychoedukationsgruppe konnte sich signifikant im Krankheitswissen steigern (d = 0,80). Behandlungseffekte zwischen 0,12 und 0,60 zeigen sich in der psychischen Gesundheit vor allem in der depressiven, aber auch in der Angst-Symptomatik. Erste Ansätze im Aufbau von Selbstwirksamkeit (d = 0,20) sind erkennbar. Schlussfolgerung: Das Hauptziel einer Verbesserung des Krankheitswissens konnte durch das Gruppenprogramm erreicht werden. Insgesamt bestätigen die Studienergebnisse die Bedeutung psychoedukativer Interventionen in der stationären Behandlung schwerstbeeinträchtigter Patienten mit Ängsten.
Keywords: Angststörungen; Psychoedukation; kognitiv-behaviorale Gruppentherapie; Evaluation

Psychogenic nonepileptic seizures: clinical characteristics and outcome - Volbers, Bastian; Walther, Katrin; Kurzbuch, Katrin; Erdmann, Laura; Gollwitzer, Stephanie; Lang, Johannes; Onugoren, Muejgan Dogan; Schwarz, Michael; Schwab, Stefan; Hamer, Hajo (Brain and Behavior, 2022)
Background: Clinical characteristics, outpatient situation, and outcome in patients with psychogenic nonepileptic seizures (PNES) remain to be elucidated. Methods: Patients diagnosed with PNES after video-electroencephalography (EEG) monitoring (VEM) 03/2000–01/2016 at the Erlangen Epilepsy Center were surveyed between June 2016 and February 2017. Primary outcome was PNES cessation defined as no PNES episodes within > = 12 months prior to the interview. Secondary outcome variables included quality of life (QoL) and dependency. Sensitivity analysis included patients with proven PNES during VEM without comorbid epilepsy. Results: Ninety-nine patients were included (median age 38 (interquartile range (IQR 29–52)) years; 68 (69%) females, follow-up 4 (IQR 2.1–7.7) years). Twenty-eight (28%) patients suffered from comorbid epilepsy. Twenty-five (25%) patients reported PNES cessation. Older age at symptom onset (odds ratio (OR) related to PNES cessation: 0.95 (95% CI 0.90–0.99)), comorbid epilepsy (OR 0.16 (95% CI 0.03–0.83)), anxiety disorder (OR 0.15 (95% CI 0.04–0.61)), and tongue biting (OR 0.22 (95% CI 0.03–0.91)) remained independently associated with ongoing PNES activity after adjustment. Sensitivity analysis (n = 63) revealed depressive disorder (OR 0.03 (95% CI 0.003–0.34)) instead of anxiety as independent predictor, while this seemed relevant only in patients older than 26 years at onset (OR 0.04 (95% CI 0.002–0.78) versus OR 0.21 (95% CI 0.02–1.84) in patients younger than 26 years). PNES cessation was associated with increased median QoL (8 (IQR 7–9) versus 5.5 (IQR 4–7); p <.001) and an increased frequency of financial independency (14 (56%) versus 21 (28%); p =.01). Conclusions: We found poor outcomes in PNES especially in older patients at onset with comorbid depressive disorder. Comorbid epilepsy also seems to be a major risk factor of ongoing PNES activity, which in turn affects patients’ daily living.
CRIS-Team Scopus Importer:2022-04-22
Keywords: activities of daily living; mental disorders; nonepileptic seizures; patient-relevant outcome; prognosis

Psychological and physical quality of life in actual versus potential liver living donors: A prospective, controlled, multicentric study - Kröncke, S.; Erim, Yesim; Beckmann, M.; Nadalin, S.; Paul, A.; Fischer, L.; Nashan, B.; Senf, W.; Schulz, K. H. (Transplantationsmedizin, 2009)

Psychological processing of a kidney transplantation, perceived quality of life, and immunosuppressant medication adherence - Scheel, Jennifer Felicia; Schieber, Katharina; Reber, Sandra Therese; Jank, Sabine; Eckardt, Kai-Uwe; Grundmann, Franziska; Vitinius, Frank; De Zwaan, Martina; Bertram, Anna; Erim, Yesim (Patient Preference and Adherence, 2019)
Introduction: Though psychosocial well-being and quality of life generally improve after transplantation, a relevant proportion of patients suffers from psychosocial problems. Further analysis of the psychological coping after kidney transplantation is needed to identify patients at risk. The aim of this study was to examine the psychological response after kidney transplantation and its associations with health-related quality of life and immunosuppressant medication adherence.
CRIS-Team WoS Importer:2019-06-04

Psychological strain in urgent indications for living donor liver transplantation - Erim, Yesim; Beckmann, Mingo Bianca; Kroencke, Sylvia; Valentin-Gamazo, Camino; Malago, Massimo; Bröring, Dieter C.; Rogiers, Xavier; Frilling, Andrea; Broelsch, Christoph E.; Schulz, Karl-Heinz (Liver Transplantation, 2007)

Psychometric properties of the German Penn Alcohol Craving Scale - Nakovics, Helmut; Hoffmann, Sabine; Koopmann, Anne; Bach, Patrick; Abel, Martin; Sommer, Wolfgang H.; Kiefer, Falk; Weinland, Christian; von Zimmermann, Claudia; Siegmann, Eva-Maria; Kornhuber, Johannes; Mühle, Christiane; et al. (Alcohol and Alcoholism, 2023)
Craving for alcohol is an important diagnostic criterion in alcohol use disorder (AUD) and an established predictor of future relapse. The 5-item Penn Alcohol Craving Scale (PACS) is one of the most widely used questionnaires to quantify craving and has been translated into different languages. It is assumed that the PACS constitutes one factor, although theoretical considerations suggest an additional second factor. We conducted stability and factor analyses (principal component and confirmatory factor analyses) of the German PACS (PACS-G) in samples of patients with AUD from the following three German study sites: Erlangen, N = 188 (mean age: 47.1 years, 43.5% female); Mannheim, N = 440 (45.5 years, 28.6% female); Hannover, N = 107 (48.1 years, 48.6% female). In our samples, the 2-factor solution of the PACS-G version is more stable than the internationally assumed 1-factor solution. The resulting two PACS-G subscores ‘difficulty to resist’ (items 4 and 5) and ‘thoughts about alcohol’ (items 1, 2, and 3) have an internal consistency (Cronbach’s alpha) of 0.80 ≤ α ≤ 0.90, m = 0.86 and 0.86 ≤ α ≤ 0.91, m = 0.89 with an overlap of R2 = 62%. We found good convergent validity assessed via the Craving Automatized Scale-Alcohol and the Obsessive-Compulsive Drinking Scale, but also correlations with depression and anxiety assessed via the Beck’s Depression and Anxiety Inventories. This study is the first to provide evidence for a 2-factor solution (‘difficulty to resist’ and ‘thoughts about alcohol’) underlying the PACS-G version.
CRIS-Team Scopus Importer:2023-12-15
Keywords: alcohol dependence; alcohol use disorder; craving

Psychooncological counseling and treatment as part of the Comprehensive Cancer Center (CCC): Multicenter study to detect the psycho-oncological needs, indications and using - Buettner-Teleaga, A.; Weis, J.; Goerling, U.; Hornemann, B.; Erim, Yesim; Beckmann, Matthias; Senf, B.; Gresch, C.; Schulz-Kindermann, K.; Friedrich, H. -C.; Albus, C.; Geiser, F.; et al. (2016)
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Psychopharmakologische Behandlung von Menschen mit schwerer Demenz - Diehl, Kristina; Kratzer, André; Donath, Carolin; Maas, Renke; Fromm, Martin; Kornhuber, Johannes; Grässel, Elmar (Deutsches Ärzteblatt international, 2022)
CRIS-Team Scopus Importer:2022-11-25

Psychosocial Aspects of Organ Transplantation - de Zwaan, Martina; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2018)

Psychosocial burden and working conditions during the COVID-19 pandemic in Germany: The VOICE survey among 3678 health care workers in hospitals - Morawa, Eva; Schug, Caterina; Geiser, Franziska; Beschoner, Petra; Jerg-Bretzke, Lucia; Albus, Christian; Weidner, Kerstin; Hiebel, Nina; Borho, Andrea; Erim, Yesim (Journal of psychosomatic research, 2021)
Objective: The aim of this cross-sectional web-based study was to examine self-reported mental distress, psychosocial burdens, working conditions and potential risk and protective factors for depressive and anxiety symptoms during the COVID-19 pandemic in health care workers (HCW). Methods: In the largest survey on mental health of HCW conducted during the first wave of COVID-19 in Europe (N = 8071 HCW), we investigated depressive (Patient Health Questionnaire-2, PHQ-2), and anxiety symptoms (Generalized Anxiety Disorder-2, GAD-2), working conditions, and psychosocial burden of 3678 HCW of three health care professions in hospitals: physicians (n = 1061), nurses (n = 1275), and medical technical assistants (MTA, n = 1342). Results: The prevalence of clinically significant levels of depressive and anxiety symptoms was 17.4% and 17.8% for physicians, 21.6% and 19.0% for nurses, and 23.0% and 20.1% for MTA, respectively. All three professions demonstrated significantly elevated PHQ-2 and GAD-2 scores, when compared with general German population before the pandemic, but lower scores in relation to that during the pandemic. Multiple linear regression analyses revealed that higher levels of depressive symptoms were associated with insufficient recovery during leisure time, increased alcohol consumption, and less trust in colleagues in difficult situations at work. In addition, elevated anxiety scores were related to increased fear of becoming infected with COVID-19. Conclusion: During the pandemic HCW demonstrated a lower burden of mental distress compared to the general population. Nevertheless, a high percentage of HCW demonstrates psychosocial distress, so that the establishment of regular mental health screening and prevention programmes for HCW is indicated.
CRIS-Team Scopus Importer:2021-03-26
Keywords: Anxiety; COVID-19; Depression; Health care; Mental health; Working conditions

Psychosocial Diagnosis and Treatment Before and After Organ Transplantation - Zwaan, Martina de; Erim, Yesim; Kröncke, Sylvia; Vitinius, Frank; Buchholz, Angela; Nöhre, Mariel (Deutsches Ärzteblatt international, 2023)
BACKGROUND: This new clinical practice guideline concerns the psychosocial diagnosis and treatment of patients before and after organ transplantation. Its objective is to establish standards and to issue evidence-based recommendations that will help to optimize decision making in psychosocial diagnosis and treatment. METHODS: For each key question, the literature was systematically searched in at least two databases (Medline, Ovid, Cochrane Library, and CENTRAL). The end date of each search was between August 2018 and November 2019, depending on the question. The literature search was also updated to capture recent publications, by using a selective approach. RESULTS: Lack of adherence to immunosuppressant drugs can be expected in 25-30% of patients and increases the odds of organ loss after kidney transplantation (odds ratio 7.1). Psychosocial interventions can significantly improve adherence. Metaanalyses have shown that adherence was achieved 10-20% more frequently in the intervention group than in the control group. 13-40% of patients suffer from depression after transplantation; mortality in this group is 65% higher. The guideline group therefore recommends that experts in psychosomatic medicine, psychiatry, and psychology (mental health professionals) should be involved in patient care throughout the transplantation process. CONCLUSION: The care of patients before and after organ transplantation should be multidisciplinary. Nonadherence rates and comorbid mental disorders are common and associated with poorer outcomes after transplantation. Interventions to improve adherence are effective, although the pertinent studies display marked heterogeneity and a high risk of bias.
CRIS-Team Scopus Importer:2023-08-25

Psychosocial distress and utilization of professional psychological care in cancer patients: An observational study in National Comprehensive Cancer Centers (CCCs) in Germany. - Weis, Joachim; Hoenig, Klaus; Bergelt, Corinna; Faller, Hermann H.; Brechtel, Anette; Hornemann, Beate; Stein, Barbara; Teufel, Martin; Goerling, Ute; Erim, Yesim; Geiser, Franziska; Niecke, Alexander; et al. (Psycho-Oncology, 2018)

Psychosocial Evaluation of Transplant Patients - Recommendations for the Guidelines for Organ Transplantation - Kroencke, Sylvia; Greif-Higer, Gertrud; Albert, Wolfgang; De Zwaan, Martina; Erim, Yesim; Eser-Valeri, Daniela; Papachristou, Christina; Petersen, Irene; Schulz, Karl-Heinz; Tigges-Limmer, Katharina; Vitinius, Frank; Ziegler, Kristin; et al. (Psychotherapie Psychosomatik Medizinische Psychologie, 2018)
Keywords: organ transplantation; psychosocial evaluation; recommendations

Psychosocial impact of living donation - Erim, Yesim; Senf, Wolfgang; Heitfeld, M. (Transplantation Proceedings, 2003)

Psychosocial impact of prognostic genetic testing in the care of uveal melanoma patients: protocol of a controlled prospective clinical observational study - Erim, Yesim; Scheel, Jennifer; Breidenstein, Anja; Metz, Claudia H. D.; Lohmann, Dietmar; Friederich, Hans-Christoph; Tagay, Sefik (BMC Cancer, 2016)
EVALuna2:24030

Psychosocial impact of prognostic genetic testing in uveal melanoma patients: a controlled prospective clinical observational study - Lieb, Marietta; Tagay, Sefik; Breidenstein, Anja; Hepp, Tobias; Le Guin, Claudia H.D.; Scheel, Jennifer Felicia; Lohmann, Dietmar R.; Bornfeld, Norbert; Teufel, Martin; Erim, Yesim (BMC Psychology, 2020)
BACKGROUND: The risk of metastases in uveal melanoma can accurately be estimated through genetic analysis of the tumor. A growing number of patients decide to receive information on their prognosis, although this can be extremely burdensome. Studies on the psychosocial impact of testing are sparse. The objective of this study was to examine traits of patients opting for prognostication, to investigate its psychosocial impact and the use of psycho-oncological services over time. We further examined characteristics of patients utilizing these services and risk factors of prolonged psychological distress. DESIGN AND METHODS: This study is a non-randomized controlled prospective clinical observational trial. Patients availing for prognostication formed the test group, while those who opted out constituted the observational group. The psychosocial impact of genetic testing was assessed with the following variables: resilience, social support, fear of tumor progression, depression, general distress, health-related quality of life, estimation of the perceived risk, and the utilization of psycho-oncological interventions. Data were assessed at five different time points over a period of 12 months. We applied binary logistic regression analysis, multiple linear regressions and a mixed model. RESULTS: Of 175 patients, 63 decided to obtain prognostic information. Treatment method (enucleation > brachytherapy), lower social support and higher general distress could significantly predict patient's choice for prognostic testing. After result announcement, perceived risk of metastases was significantly increased in patients with poor prognosis, while it decreased in those with good prognosis. Overall, a significant decrease over time appeared concerning fear of progression, general distress, depression and anxiety. Mental quality of life increased over time. The utilization of psycho-oncological interventions increased significantly after prognostication; however, this was equivalent in the test and observational groups. Female sex, higher general distress and higher anxiety predicted greater use of psycho-oncological interventions. DISCUSSION: Availing of prognostic testing is not associated with poorer subsequent psychological well-being. It rather may help to alleviate distress and promote a more realistic risk perception. However, psychological support should be available to all patients, independent of prognosis and treatment, especially considering that patients with low social support and high distress increasingly opt for prognostication.
CRIS-Team Scopus Importer:2020-02-11
Keywords: Controlled prospective clinical observation trial; Prognostic genetic testing; Psycho-oncological intervention; Psychosocial impact; Uveal melanoma

Psychosocial impact of the covid‐19 pandemic on healthcare workers and initial areas of action for intervention and prevention—the egepan/voice study - Jerg‐bretzke, Lucia; Kempf, Maximilian; Jarczok, Marc Nicolas; Weimer, Katja; Hirning, Christian; Gündel, Harald; Erim, Yesim; Morawa, Eva; Geiser, Franziska; Hiebel, Nina; Weidner, Kerstin; Albus, Christian; et al. (International Journal of Environmental Research and Public Health, 2021)
Introduction: Epidemics lead to an increase in occupational stress and psychological strain among healthcare workers. However, the impact of a pandemic outbreak on healthcare systems is yet to be clearly defined. Therefore, this work aims to describe and analyze specific areas of workload among different groups of healthcare workers during the first wave of the COVID‐19 pandemic. Methods: A sample of N = 8088 persons working in the German‐speaking healthcare sector participated in the VOICE/egePan online survey, which addressed the impact of the COVID‐ 19 pandemic during the second quarter of 2020. We used 15 self‐constructed items, based on the work of Matsuishi et al. (2012), to identify potential COVID‐19‐specific topics. Results: N = 7542 records of healthcare workers were analyzed. Of these, 60.80% reported, retrospectively, an increase in stress since the outbreak of the pandemic. Problem areas tended to be indicated more frequently by the women surveyed than by the men. Nurses, paramedics and medical technicians reported the highest fear of infecting others while physicians reported the highest fear of physical or mental exhaustion. With respect to age, older respondents indicated less fear and felt more protected. Men and people living alone were more likely to use dysfunctional coping strategies. Migrants reported a higher fear of becoming infected or infecting others as well as they reported about increased levels of smoking. Discussion: Retrospectively, the COVID‐19 pandemic led to an increase in stress among healthcare workers. Problem areas have different focuses with regard to different living situations, environmental conditions and professions. In order to lay the best basis for healthy and efficient work, it seems necessary to take measures especially tailored to the needs of different groups of healthcare workers.
CRIS-Team Scopus Importer:2021-10-22
Keywords: COVID‐19; Healthcare workers; Mental health; Occupational stress

Psychosocial Multi-component Intervention for People with Dementia: Comparison with and without Robotic Assistance - Dirks, Kaja; Wasic, Catharina; Grassel, E. (ZEITSCHRIFT FUR GERONTOLOGIE UND GERIATRIE, 2022)
CRIS-Team WoS Importer:2022-09-16

Psycho-social support needs, depression and utilization of psychological/psychiatric treatment in cancer patients in Germany: A register-based cross-cultural study - Morawa, Eva; Erim, Yesim (2018)
EVALuna2:214431

Psychosocial Variables Associated with Immunosuppressive Medication Non-Adherence after Renal Transplantation. - Scheel, Jennifer Felicia; Schieber, Katharina; Reber, Sandra; Stoessel, Lisa; Waldmann, Elisabeth; Jank, Sabine; Eckardt, Kai-Uwe; Grundmann, Franziska; Vitinius, Frank; de Zwaan, Martina; Bertram, Anna; Erim, Yesim (Frontiers in Psychiatry, 2018)

Psychosomatic aspects of living donor liver transplantation - Erim, Yesim; Beckmann, M.; Gerken, G.; Paul, A.; Senf, W.; Beckebaum, S. (Chirurg, 2010)
Keywords: Transplantation; Liver; Living donor; Donor; Psychosomatic medicine

Psychosomatic Aspects of Organ Transplantation - Erim, Yesim; Beckmann, Mingo; Klein, Christian; Paul, Andreas; Beckebaum, Susanne (Psychotherapie Psychosomatik Medizinische Psychologie, 2013)

Psychosomatic Case Conference Activity during Acute internal Medical Treatment for severe Anorexia Nervosa - Gerlach, G.; Jochum, C.; Gerken, G.; Erim, Yesim; Senf, W. (Psychotherapie Psychosomatik Medizinische Psychologie, 2011)

Psychosomatic Evaluation of Patients Awaiting Lung Transplantation - Erim, Yesim; Beckmann, M.; Marggraf, G.; Senf, W. (Transplantation Proceedings, 2009)
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Psychosomatic evaluation of transplant candidates: transplant evaluation rating scale objectifies the clinical decision - Beckmann, M.; Kroencke, S.; Schulz, K. -H.; Erim, Yesim (Transplant International, 2010)

Psychosomatic medicine and transplant patients - what is known and what is needed - Bernd, Johann; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2001)
Keywords: organ transplantation; psychiatric morbidity; compliance social support; prognostic psychosocial factors; psychotherapeutic interventions

Psychosomatische Betreuung von Transplantationspatienten - Erim, Yesim; Köllner, Volker (Praxis der Psychotherapie, ein integratives Lehrbuch der Psychiatrie, 2.-5. Auflage, 2011)

Psychotherapie mit Migranten - Erim, Yesim (Praxis der Psychotherapie, ein integratives Lehrbuch der Psychotherapie, 2011)

Psychotherapy and Religion: A Representative Survey Among Psychotherapists in Southern Germany - Marquardt, Michael; Demling, Joachim (Psychotherapie Psychosomatik Medizinische Psychologie, 2016)
Objective: Religion and spirituality play an appreciable role as a problem area or as a resource for patients with mental disorders. It is therefore of interest what attitudes psychotherapists assume towards this complex range of issues in their work, but also in their personal lives. The majority of empirical studies on this subject originate from the USA, with little data being available from Europe and Germany. Our own survey among practising psychotherapists was designed to elucidate these questions. Method and Study Population: A cross-sectional study was conducted in the form of a written survey of all accessible practising psychotherapists in the area of Northern Bavaria (Franconian administrative districts; n=1 081, return rate 65%). Results: Around two-thirds of the therapists consider religion to be an important subject in psychotherapy, but only one-fifth of them routinely take a history of the patients' religious beliefs. The therapists' own closeness to religion correlates positively with the tendency to incorporate religion in their therapy. In around one-third of the therapists, religion holds an important place within their own world view, although significantly fewer psychotherapists than the general population of Franconia are bound to a specific confession. Around one-quarter had at least once consulted a pastor due to a patient, while each seventh therapist had at least once actively mediated contact to a pastor. Conclusions: Religion is a subject that is relevant for therapeutic practice, but a history of religious beliefs is rarely taken on a routine basis. The incorporation of religion into psychotherapy correlates with religious characteristics of the therapists ("personal bias"). There appears to be a "religiosity gap" between psychotherapists and the general population. Advanced training on the subject of "religion/spirituality" and increased consideration in supervision may counteract the danger of religious needs and religion-related resources of patients being neglected.
EVALuna:34141

Psychotherapy for minority patients. Cross cultural affairs in psychotherapy - Erim, Yesim; Senf, Wolfgang (Psychotherapeut, 2002)
Keywords: immigrants; cross-cultural psychotherapy; cross-cultural psychodynamics; knowledge of specific cultural issues; culture sensitive interventions

Psychotherapy with Immigrants and Traumatized Refugees - Erim, Yesim; Morawa, Eva (Psychotherapie Psychosomatik Medizinische Psychologie, 2016)
EVALuna2:24044

Publisher Correction: Gene expression imputation across multiple brain regions provides insights into schizophrenia risk (Nature Genetics, (2019), 51, 4, (659-674), 10.1038/s41588-019-0364-4) - Huckins, Laura M.; Dobbyn, Amanda; Hoffman, Gabriel; Wang, Weiqing; Pardiñas, Antonio F.; T. Nguyen, Hoang; Girdhar, Kiran; Boocock, James; Roussos, Panos; Fromer, Menachem; Kramer, Robin; Domenici, Enrico; et al. (Nature Genetics, 2019)
In the HTML version of the article originally published, the author group ‘The Schizophrenia Working Group of the Psychiatric Genomics Consortium’ was displayed incorrectly. The error has been corrected in the HTML version of the article.
CRIS-Team Scopus Importer:2019-05-28

Pulsed Arterial Spin Labeling and Segmented Brain Volumetry in the Diagnostic Evaluation of Frontotemporal Dementia, Alzheimer’s Disease and Mild Cognitive Impairment - Marterstock, Dominique; Knott, Michael; Lang, Stefan; Oberstein, Timo; Kornhuber, Johannes; Dörfler, Arnd; Schmidt, Manuel; Hölter, Philip (Tomography, 2022)
Background: Previous studies suggest that brain atrophy can not only be defined by its morphological extent, but also by the cerebral blood flow (CBF) within a certain area of the brain, including white and gray matter. The aim of this study is to investigate known atrophy patterns in different forms of dementia and to compare segmented brain volumetrics and pulsed arterial spin labeling (pASL) data to explore the correlation between brain maps with atrophy and this non-contrast-enhanced brain-perfusion method. Methods: Our study comprised 17 patients with diagnosed cognitive impairment (five Alzheimer’s disease = AD, five frontotemporal dementia = FTD, seven mild cognitive impairment = MCI) and 19 healthy control subjects (CO). All patients and controls underwent 4D-pASL brain-perfusion MR imaging and T1w MPRAGE. The data were assessed regarding relative brain volume on the basis of 286 brain regions, and absolute and relative cerebral blood flow (CBF/rCBF) were derived from pASL data in the corresponding brain regions. Mini-Mental State Examination (MMSE) was performed to assess cognitive functions. Results: FTD patients demonstrated significant brain atrophy in 43 brain regions compared to CO. Patients with MCI showed significant brain atrophy in 18 brain regions compared to CO, whereas AD patients only showed six brain regions with significant brain atrophy compared to CO. There was good correlation of brain atrophy and pASL perfusion data in five brain regions of patients with diagnosed FTD, especially in the superior temporal gyrus (r = 0.900, p = 0.037), the inferior frontal white matter (pars orbitalis; r = 0.968, p = 0.007) and the thalami (r = 0.810, p = 0.015). Patients with MCI demonstrated a correlation in one brain region (left inferior fronto-occipital fasciculus; r = 0.786, p = 0.036), whereas patients with diagnosed AD revealed no correlation. Conclusions: pASL can detect affected brain regions in cognitive impairment and corresponds with brain atrophy, especially for patients suffering from FTD and MCI. However, there was no correlation of perfusion alterations and brain atrophy in AD. pASL perfusion might thus represent a promising tool for noninvasive brain-perfusion evaluation in specific dementia subtypes as a complimentary imaging-based bio marker in addition to brain volumetry.
CRIS-Team Scopus Importer:2022-02-11
Keywords: Alzheimer’s disease; Brain volumetry; Dementia; Frontotemporal dementia; Mild cognitive impairment; Pulsed arterial spin labeling

Quality of life and psychiatric complications after adult living donor liver transplantation - Erim, Yesim; Beckmann, Mingo; Valentin-Gamazo, Camino; Malago, Massimo; Frilling, Andrea; Schlaak, Joerg F.; Gerken, Guido; Broelsch, Christoph E.; Senf, Wolfgang (Liver Transplantation, 2006)

Quality of Life and Sense of Coherence in Cancer Patients of German, Turkish and Polish Origin—A Cross-Sectional Study - Lieb, Marietta; Erim, Yesim; Morawa, Eva (International Journal of Environmental Research and Public Health, 2023)
Background: Due to a variety of symptoms and side-effects of cancer treatment, quality of life can be considerably impaired in cancer patients. Especially, cancer patients with a migration background seem to be at risk. The objective of our study is to investigate the quality of life and sense of coherence in adult cancer patients of German, Turkish and Polish origin. Methods: We assessed sociodemographic, migration-specific and cancer-related parameters. Quality of life was measured via the EORTC QLQ-C30, sense of coherence was measured with the SOC-13. Results: We included 227 patients in the study (59.5% native Germans, 40.5% with migration background). Native Germans did not differ in quality of life compared to all migrants. However, more nausea and vomiting (NV) and higher appetite loss (AP) was found in Turkish migrants compared to Polish migrants and native Germans. For sense of coherence, we observed significantly higher scores for native Germans compared to all migrants. Turkish migrants had significantly lower scores compared to native Germans. Conclusions: A Turkish migration background seems to play an important role in the perception of symptoms, especially of nausea and vomiting and appetite loss. Culture-specific aspects should be considered in cancer care.
CRIS-Team Scopus Importer:2023-02-24
Keywords: cancer; German; migration background; Polish; quality of life; sense of coherence; Turkish

Quality of life assessment in family members of patients with chronic wounds - Erfurt-Berge, Cornelia; Ronicke, Moritz; Richter-Schmidinger, Tanja; Walther, Felix; Renner, Regina (European Journal of Dermatology, 2019)
Familial caregivers are often directly involved in treatment of patients with chronic wounds, however, less is known about their personal impairment, and specific support is lacking for these important members of the therapeutic team regarding wound care. The aim of this study was to investigate the influence of wound care provided by family members on their quality of life, and to create a suitable questionnaire to describe the affected personal aspects. A five-part questionnaire, named ELWA, was created by the authors and answered by 30 familial caregivers of 30 respective patients with chronic leg ulcers. One third of the caregivers reported receiving no medical advice about detailed wound care at all. A lack of information regarding details of the disease correlated with personal strain. Additional costs, anxiety, frustration, and reduced spare-time activities were among the top-rated factors affecting quality of life of family members. The results from this newly created questionnaire point out the needs of familial caregivers of patients with chronic wounds and may help to establish individual support. Implementation of clinical treatment strategies is planned through multicentre application.
CRIS-Team Scopus Importer:2019-12-13
Keywords: chronic wounds; family member; leg ulcer; quality of life; wound care

Quantifying progression in primary progressive aphasia with structural neuroimaging - Lombardi, Jolina; Mayer, Benjamin; Semler, Elisa; Anderl-Straub, Sarah; Uttner, Ingo; Kassubek, Jan; Diehl-Schmid, Janine; Danek, Adrian; Levin, Johannes; Fassbender, Klaus; Fliessbach, Klaus; Schneider, Anja; et al. (Alzheimers & Dementia, 2021)
Introduction: The term primary progressive aphasia (PPA) sums up the non-fluent (nfv), the semantic (sv), and the logopenic (lv) variant. Up to now, there is only limited data available concerning magnetic resonance imaging volumetry to monitor disease progression. Methods: Structural brain imaging and an extensive assessment were applied at baseline and up to 4-year(s) follow-up in 269 participants. With automated atlas-based volumetry 56 brain regions were assessed. Atrophy progression served to calculate sample sizes for therapeutic trials. Results: At baseline highest atrophy appeared in parts of the left frontal lobe for nfvPPA (–17%) and of the left temporal lobe for svPPA (–34%) and lvPPA (–24%). Severest progression within 1-year follow-up occurred in the basal ganglia in nfvPPA (–7%), in the hippocampus/amygdala in svPPA (–9%), and in (medial) temporal regions in lvPPA (–6%). Conclusion: PPA presents as a left-dominant, mostly gray matter sensitive disease with considerable atrophy at baseline that proceeds variant-specific.
CRIS-Team Scopus Importer:2021-04-16
Keywords: atlas-based volumetry; disease progression; frontotemporal dementia; longitudinal magnetic resonance imaging; primary progressive aphasia; sample size calculation

Quantile-based classification of Alzheimer's disease, frontotemporal dementia and asymptomatic controls from SPECT data - Geller, Dieter; Platsch, Günther; Kornhuber, Johannes; Kuwert, Torsten; Merhof, Dorit (2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop, NSS/MIC/RTSD 2016, 2017)
Nuclear imaging techniques, namely single photon emission computed tomography (SPECT) and positron emission tomography (PET), are commonly used for the study of neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). Many methods have been proposed to identify different types of dementia based on SPECT and PET images. In order to cope with the low number of datasets compared to the high number of independent variables (voxels of the dataset), they either perform a dimensionality reduction prior to classification, which implies identical influence of all available datasets, or try to extract the relevant variables for the prediction, which may be affected by statistical fluctuation resulting from mislabeled data or intrinsic noise within data samples. In order to overcome these limitations, this paper presents an alternative method for classification of SPECT image data of asymptomatic controls (HC), AD and FTD participants. The proposed method produces a voxel mask that weights or ignores voxels according to their relevance for classification. The algorithm is based on quantiles and is less sensitive to the non-Gaussian statistical distribution of the classes to separate, which is a very desirable in case of dementia classification. Special care is taken to assess the robustness of the proposed approach. The classification accuracy assessed with bootstrap resampling is presented and the robustness against outliers and misdiagnosed training samples is investigated and compared with a PCA-MVA based approach. As a result, the proposed approach shows comparable results with respect to robustness, but better classification accuracy than PCA-based approaches.
CRIS-Team Scopus Importer:2023-03-23
Keywords: Alzheimer's disease; Frontotemporal dementia; Quantile-based classification; SPECT

Quantitative EEG may predict weaning failure in ventilated patients on the neurological intensive care unit - Welte, Tamara; Gabriel, Maria; Hopfengaertner, Ruediger; Rampp, Stefan; Gollwitzer, Stephanie; Lang, Johannes; Stritzelberger, Jenny; Reindl, Caroline; Madzar, Dominik; Sprügel, Maximilian; Huttner, Hagen; Kuramatsu, Joji; et al. (Scientific Reports, 2022)
Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann–Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients.
CRIS-Team Scopus Importer:2022-05-20

Quantitative validation of the n-butanol sniffin’ sticks threshold pens. - Denzer, Melanie; Gailer, Stefan; Kern, David W.; Schumm, L. Philip; Thürauf, Norbert; Kornhuber, Johannes; Büttner, Andrea; Beauchamp, Jonathan (Chemosensory Perception, 2014)
Odorant pens are used by medical practitioners and researchers to assess olfactory dysfunction. Despite their routine use, there are currently no data on the gas-phase odorant concentrations released from the pen tips or whether these concentrations scale linearly with the aqueous-phase concentrations inside the pens. The commercially available Sniffin’ Sticks odor threshold test containing n-butanol was chosen for evaluation. The gas-phase concentration of n-butanol at the tip of each pen was measured directly in a new set of pens via proton-transfer-reaction mass spectrometry (PTR-MS). Measurements were additionally made on the same pens after 6 months and two older pen sets, namely a 3-year-old (used) and 4-year-old (new) set. Furthermore, application-related tests were made to determine the performance of the pens during routine use and under stress. These data demonstrate that the gas-phase n-butanol concentrations of the threshold pens are linear over the entire set, both for brand-new pens and 6 months later; this reflects the expected performance that was previously only assumed. Furthermore, the application–simulation tests demonstrated a good performance of the pens when used according to their intended protocol. Measurements of the older pen sets suggest that storage conditions are more critical than usage for pen stability. The present findings confirm that the n-butanol odorant pens are an appropriate tool for threshold testing, provided they are stored and handled correctly.<br

Quantitative validation of the n-butanol Sniffin' Sticks threshold pens - Denzer, Melanie; Gailer, Stefan; Kern, David W.; Schumm, L. Philip; Thürauf, Norbert; Kornhuber, Johannes; Büttner, Andrea; Beauchamp, Jonathan (Chemosensory Perception, 2014)
Odorant pens are used by medical practitioners and researchers to assess olfactory dysfunction. Despite their routine use, there are currently no data on the gas-phase odorant concentrations released from the pen tips or whether these concentrations scale linearly with the aqueous-phase concentrations inside the pens. The commercially available Sniffin' Sticks odor threshold test containing n-butanol was chosen for evaluation. The gas-phase concentration of n-butanol at the tip of each pen was measured directly in a new set of pens via proton-transfer-reaction mass spectrometry (PTR-MS). Measurements were additionally made on the same pens after 6 months and two older pen sets, namely a 3-year-old (used) and 4-year-old (new) set. Furthermore, application-related tests were made to determine the performance of the pens during routine use and under stress. These data demonstrate that the gas-phase n-butanol concentrations of the threshold pens are linear over the entire set, both for brand-new pens and 6 months later; this reflects the expected performance that was previously only assumed. Furthermore, the application-simulation tests demonstrated a good performance of the pens when used according to their intended protocol. Measurements of the older pen sets suggest that storage conditions are more critical than usage for pen stability. The present findings confirm that the n-butanol odorant pens are an appropriate tool for threshold testing, provided they are stored and handled correctly. © 2014 The Author(s).
UnivIS-Import:2015-04-14:Pub.2014.nat.dchph.llmch.quanti
Keywords: n-Butanol; Odor threshold test; Olfaction; PTR-MS; Sniffin' Sticks

Randomized controlled trial of pregabalin for analgesia after surgical treatment of intervertebral disc disease in dogs - Schmierer, Philipp A.; Tuensmeyer, Julia; Tipold, Andrea; Hartnack-Wilhelm, Sonja; Lesczuk, Piotr; Kaestner, Sabine B. R. (Veterinary Surgery, 2020)
Objective: To assess the effect of perioperative pregabalin on pain behavior in dogs after intervertebral disc surgery. Study design: Prospective, randomized, controlled clinical trial with a blinded observer. Animals: Forty-six client-owned dogs undergoing intervertebral disc surgery. Methods: Dogs were randomly assigned to two groups, with the placebo group receiving opioids alone and the pregabalin group receiving opioids plus pregabalin. Opioid analgesia consisted of 0.6 mg/kg l-methadone given intravenously at anesthetic induction, followed by 0.2 mg/kg given at 8, 16, and 24 hours after extubation and fentanyl patches applied at the end of surgery. Pregabalin was given orally (4 mg/kg) 1 hour before anesthesia, followed by postoperative treatment three times per day (4 mg/kg) for 5 days. The outcome measures were the treatment-group differences in peri-incisional mechanical sensitivity and Glasgow Composite Measure Pain Scale (CMPS-SF) assessed during the first 5 postoperative days. Pregabalin serum concentrations were measured after 24, 72, and 120 hours. Results: Pregabalin reduced pain levels in the treatment group by a mean of 2.5 CMPS-SF units (95% confidence interval [CI] = −3.19 to −1.83, P <.001) compared with the control group during the study period. Pregabalin increased the mechanical nociceptive threshold by a mean of 6.89 N per day (95% CI = 1.87-11.92, P <.001) and of 7.52 N per day (95% CI = 2.29-12.77, P <.001) during the study period, depending on location. Mean levels of serum pregabalin were 5.1, 4.71, and 3.68 μg/mL at 24, 72, and 120 hours postoperatively, respectively. Conclusion: Postoperative signs of pain after surgical treatment of intervertebral disc herniation (IVDH) were reduced when dogs received perioperative pregabalin rather than opioids alone. Clinical significance: Perioperative pregabalin reduces postoperative pain after surgical treatment of IVDH.
CRIS-Team Scopus Importer:2020-05-12

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease - Sims, Rebecca; Van Der Lee, Sven J.; Naj, Adam C.; Bellenguez, Celine; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W.; Boland, Anne; Raybould, Rachel; Bis, Joshua C.; Martin, Eden R.; Grenier-Boley, Benjamin; et al. (Nature Genetics, 2017)
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases= 0.0059, MAFcontrols= 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases= 0.011, MAFcontrols= 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases= 0.0143, MAFcontrols= 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
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Rasgrf2 controls dopaminergic adaptations to alcohol in mice - Easton, Alanna C.; Rotter-Neubert, Andrea; Lourdusamy, Anbarasu; Desrivieres, Sylvane; Fernandez-Medarde, Alberto; Biermann, Teresa; Fernandes, Cathy; Santos, Eugenio; Kornhuber, Johannes; Schumann, Gunter; Mueller, Christian P. (Brain Research Bulletin, 2014)
Alcohol abuse leads to serious health problems with no effective treatment available. Recent evidence suggests a role for ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) in alcoholism. Rasgrf2 is a calcium sensor and MAPK/ERK activating protein, which has been linked to neurotransmitter release and monoaminergic receptor adaptations. Rasgrf2 knock out (KO) mice do not develop a dopamine response in the nucleus accumbens after an alcohol challenge and show a reduced consumption of alcohol. The present study aims to further characterise the role of Rasgrf2 in dopaminergic activation beyond the nucleus accumbens following alcohol treatment. Using in vivo microdialysis we found that alcohol induces alterations in dopamine levels in the dorsal striatum between wildtype (WT) and Rasgrf2 KO mice. There was no difference in the expression of dopamine transporter (DAT), dopamine receptor regulating factor (DRRF), or dopamine D2 receptor (DRD2) mRNA in the brain between Rasgrf2 KO and WT mice. After sub-chronic alcohol treatment, DAT and DRRF, but not DRD2 mRNA expression differed between WT and Rasgrf2 KO mice. Brain adaptations were positively correlated with splenic expression levels. These data suggest that Rasgrf2 controls dopaminergic signalling and adaptations to alcohol also in other brain regions, beyond the nucleus accumbens.
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Rasgrf2 controls noradrenergic involvement in the acute and subchronic effects of alcohol in the brain - Easton, Alanna C.; Rotter-Neubert, Andrea; Lourdusamy, Anbarasu; Desrivieres, Sylvane; Fernandez-Medarde, Alberto; Biermann, Teresa; Fernandes, Cathy; Santos, Eugenio; Kornhuber, Johannes; Schumann, Gunter; Mueller, Christian P. (Psychopharmacology, 2014)
Alcohol addiction is a major psychiatric disease, and yet, the underlying molecular adaptations in the brain remain unclear. Recent evidence suggests a functional role for the ras-specific guanine-nucleotide releasing factor 2 (Rasgrf2) in alcoholism. Rasgrf2(-/-) mice consume less alcohol and show entirely absent dopamine responses to an alcohol challenge compared to wild types (WT).In order to further investigate how Rasgrf2 modifies the acute and subchronic effects of alcohol in the brain, we investigated its effects on the noradrenergic and serotonergic systems.We measured noradrenaline and serotonin activity in the brain by in vivo microdialysis and RNA expression by chip analysis and RT-PCR after acute and sub-chronic alcohol exposure in Rasgrf2(-/-) and WT mice.In vivo microdialysis showed a significantly reduced noradrenergic response and an absent serotonergic response in the nucleus accumbens (NAcc) and caudate putamen (CPu) after an alcohol challenge in Rasgrf2(-/-) mice. A co-expression analysis showed that there is a high correlation between Rasgrf2 and ?2 adrenoceptor RNA expression in the ventral striatum in naïve animals. Accordingly, we further assessed the role of Rasgrf2 in the response of the noradrenergic system to subchronic alcohol exposure. A decrease in ?1 adrenoceptor gene expression was seen in Rasgrf2(+/+), but not Rasgrf2(-/-) mice following alcohol exposure. Conversely, alcohol resulted in a decrease in both ?2 and ?2 adrenoceptor gene expression in knockout but not WT Rasgrf2 mice.These findings suggest that adaptations in the noradrenergic system contribute to the Rasgrf2 enhanced risk of alcoholism.
EVALuna2:23658

Rationale, Mission and Vision for a National Centre of Affective Disorders in Germany - Reif, Andreas; Baune, Bernhard T.; Deckert, Jurgen; Juckel, Georg; Kittel-Schneider, Sarah; Kircher, Tilo; Kornhuber, Johannes; Rupprecht, Rainer; Bauer, Michael (Pharmacopsychiatry, 2021)
Affective disorders are common, complex disorders representing one of the major challenges to global health in the 21st century. To mitigate the burden of disease, substantial public health efforts need to be undertaken since research on the causes and adequate treatment requires multidisciplinary approaches. These should integrate translational, and clinical research, aided by technological advancements in collecting and analysing comprehensive data. Here we present the rationale, concept, mission and vision of the recently founded National Centre of Affective Disorders (NCAD) in Germany. NCAD founding partners build on their previous successful cooperation within the German Research Network for Mental Disorders funded by the Federal Ministry of Education and Research (BMBF). They form an internationally pre-eminent network of integrative excellence, leading in science and contributing significantly to the improved care of affective disorder patients. The partners will provide complementary structures and innovative methods across the entire translational continuum from bench to clinical and real-world settings. The vision of the NCAD is to foster cross-disciplinary research from basic neuroscience to public mental health by close translational collaboration between academia, non-university research institutions, and international partners, including industry, to deliver cutting-edge research, innovative clinical services and evidence-based training to young clinicians and scientists. The mission is to accomplish research in a highly translational manner, especially with respect to clinical studies in a trans-sectoral way. This approach aims to ensure continuous improvement in the treatment and care provided to patients and an interdisciplinary environment for high-level research and education in affective disorders.
CRIS-Team WoS Importer:2021-12-24

Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms - Gerkin, Richard C.; Ohla, Kathrin; Veldhuizen, Maria G.; Joseph, Paule V.; Kelly, Christine E.; Bakke, Alyssa J.; Steele, Kimberley E.; Farruggia, Michael C.; Pellegrino, Robert; Pepino, Marta Y.; Bouysset, Cédric; Soler, Graciela M.; et al. (Chemical Senses, 2021)
In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19−; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points; C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for 50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
CRIS-Team Scopus Importer:2021-03-26
Keywords: Anosmia; Chemosensory; Coronavirus; Hyposmia; Olfactory; Prediction

Reconceptualization of the Erlangen Score for the Assessment of Dementia Risk: The ERlangen Score - Utz, Janine; Olm, Pauline; Jablonowski, Johannes; Siegmann, Eva-Maria; Spitzer, Philipp; Lewczuk, Piotr; Kornhuber, Johannes; Maler, Juan Manuel; Oberstein, Timo (Journal of Alzheimer's Disease, 2023)
BACKGROUND: The established Erlangen Score (ES) for the interpretation of cerebrospinal fluid (CSF) biomarkers in the diagnostics of Alzheimer's disease (AD) uses markers of amyloidopathy and tauopathy, equally weighted to form an easy-interpretable ordinal scale. However, these biomarkers are not equally predictive for AD. OBJECTIVE: The higher weighting of the Aβ42/Aβ40 ratio, as a reconceptualized ERlangen Score (ERS), was tested for advantages in diagnostic performance. METHODS: Non-demented subjects (N = 154) with a mean follow up of 5 years were assigned to a group ranging from 0 to 4 in ES or ERS. Psychometric trajectories and dementia risk were assessed. RESULTS: The distribution of subjects between ES and ERS among the groups differed considerably, as grouping allocated 32 subjects to ES group 2, but only 2 to ERS group 2. The discriminative accuracy between the ES (AUC 73.2%, 95% CI [64.2, 82.2]) and ERS (AUC 72.0%, 95% CI [63.1, 81.0]) for dementia risk showed no significant difference. Without consideration of the Aβ42/Aβ40 ratio in ES grouping, the optimal cut-off of the ES shifted to ≥2. CONCLUSIONS: The ERS showed advantages over the ES in test interpretation with comparable overall test performance, as fewer cases were allocated to the intermediate risk group. The established cut-off of ≥2 can be maintained for the ERS, whereas it must be adjusted for the ES when determining the Aβ42/Aβ40 ratio.
CRIS-Team Scopus Importer:2023-11-10
Keywords: Alzheimer’s disease; dementia risk; Erlangen Score; longitudinal study; neuropsychological trajectories

Reference Interval Estimation from Mixed Distributions using Truncation Points and the Kolmogorov-Smirnov Distance (kosmic) - Zierk, Jakob; Arzideh, Farhad; Kapsner, Lorenz; Prokosch, Hans-Ulrich; Metzler, Markus; Rauh, Manfred (Scientific Reports, 2020)
Appropriate reference intervals are essential when using laboratory test results to guide medical decisions. Conventional approaches for the establishment of reference intervals rely on large samples from healthy and homogenous reference populations. However, this approach is associated with substantial financial and logistic challenges, subject to ethical restrictions in children, and limited in older individuals due to the high prevalence of chronic morbidities and medication. We implemented an indirect method for reference interval estimation, which uses mixed physiological and abnormal test results from clinical information systems, to overcome these restrictions. The algorithm minimizes the difference between an estimated parametrical distribution and a truncated part of the observed distribution, specifically, the Kolmogorov-Smirnov-distance between a hypothetical Gaussian distribution and the observed distribution of test results after Box-Cox-transformation. Simulations of common laboratory tests with increasing proportions of abnormal test results show reliable reference interval estimations even in challenging simulation scenarios, when <20% test results are abnormal. Additionally, reference intervals generated using samples from a university hospital’s laboratory information system, with a gradually increasing proportion of abnormal test results remained stable, even if samples from units with a substantial prevalence of pathologies were included. A high-performance open-source C++ implementation is available at https://gitlab.miracum.org/kosmic.
CRIS-Team Scopus Importer:2020-02-14

Refining the picture of reduced alerting responses in ADHD - a single-trial analysis of event-related potentials - Heinrich, Hartmut; Busch, Katrin; Studer, Petra; Erbe, Karlheinz; Moll, Gunther; Kratz, Oliver (Neuroscience Letters, 2014)
In attention-deficit/hyperactivity disorder (ADHD), a reduced phasic alerting response (event-related potential component P3 to cue stimuli) has been reported for different subtypes and task types in a series of studies. In order to get a refined picture of this attentional deficit, which is based on the analysis of averaged event-related potentials, we studied the distribution of single-trial cue-P3 amplitudes and the relation between the cue-P3 and the neural state (EEG spectral analysis) when expecting the stimulus. Brain electrical activity was recorded in children of different ADHD subtypes (combined type, predominantly inattentive) and typically developing children while conducting the attention network test. In children with ADHD of the combined type, smaller cue-P3 amplitudes in the averaged signal were due to a larger portion of single trials with reduced cue-P3 amplitudes whereas maximum amplitudes did not differ from typically developing children. In this ADHD subtype, larger activity in the upper theta/lower alpha range (5.5-10.5Hz) was strongly associated with the range (difference between 0.9 quantile and 0.1 quantile) of the cue-P3 amplitude in single trials (correlation coefficient r=0.77) indicating a suboptimal neural state before stimulus presentation. In children with ADHD of the predominantly inattentive subtype, single-trial P3 amplitudes were comparable at lower quantiles but maximum amplitudes were reduced. This result pattern indicates an intact triggering of the cue-P3 but a reduced capacity of resource allocation for the predominantly inattentive subtype. Though findings are limited by a relative small sample size, the cue-P3 may be considered as a neurophysiological marker of alerting deficits in ADHD reflecting different underlying mechanisms in ADHD subtypes.
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Regulation of Neuronal Stem Cell Proliferation in the Hippocampus by Endothelial Ceramide - Gulbins, Anne; Grassme, Heike; Hoehn, Richard; Wilker, Barbara; Soddemann, Matthias; Kohnen, Marcus; Edwards, Michael J.; Kornhuber, Johannes; Gulbins, Erich (Cellular Physiology and Biochemistry, 2016)
Major depressive disorder is one of the most common diseases in western countries. The disease is mainly defined by its psychiatric symptoms. However, the disease has also many symptoms outside the central nervous system, in particular cardiovascular symptoms. Recent studies demonstrated that the acid sphingomyelinase/ceramide system plays an important role in the development of major depressive disorder and functions as a target of antidepressants.Here, we investigated (i) whether ceramide accumulates in endothelial cells in the neurogenetic zone of the hippocampus after glucocorticosterone-mediated stress, (ii) whether ceramide is released into the extracellular space of the hippocampus and (iii) whether extracellular ceramide inhibits neuronal proliferation. Ceramide was determined in endothelial cell culture supernatants or extracellular hippocampus extracts by a kinase assay. Endothelial ceramide in the hippocampus was analyzed by confocal microscopy of brain sections stained with Cy3-labelled anti-ceramide antibodies and FITC-Isolectin B4. Neuronal proliferation was measured by incubation of pheochromocytoma neuronal cells with culture supernatants and extracellular hippocampus extracts.Treatment of cultured endothelial cells with glucocorticosterone induces a release of ceramide into the supernatant. Likewise, treatment of mice with glucocorticosterone triggers a release of ceramide into the extracellular space of the hippocampus. The release of ceramide is inhibited by concomitant treatment with the antidepressant amitriptyline, which also inhibits the activity of the acid sphingomyelinase. Studies employing confocal microscopy revealed that ceramide is formed and accumulates exclusively in endothelial cells in the hippocampus of stressed mice, a process that was again prevented by co-application of amitriptyline. Ceramide released in the culture supernatant or into the extracellular space of the hippocampus reduced proliferation of neurons in vitro.The data suggest a novel model for the pathogenesis of major depressive disorder, i.e. the release of ceramide-enriched microvesicles from endothelial cells that negatively affect neuronal proliferation in the hippocampus, but may also induce cardiovascular disease and other systemic symptoms of patients with major depressive disorder.
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Relationship between working conditions and mental health of migrants and refugees/asylum seekers vs. natives in Europe: a systematic review - Herold, Regina; Lieb, Marietta; Borho, Andrea; Voss, Amanda; Unverzagt, Susanne; Morawa, Eva; Erim, Yesim (International Archives of Occupational and Environmental Health, 2023)
Objective: Migrants and refugees/asylum seekers make up a significant proportion of the European workforce. They often suffer from poor working conditions, which might impact mental health. The main objective of this systematic review was to summarize and analyze existing research on working conditions of migrants and refugees/asylum seekers in European host countries and compare them to those of natives. Furthermore, the relationship between working conditions and mental health of migrants/refugees/asylum seekers and natives will be compared. Methods: Three electronic databases (PubMed/MEDLINE, PsycInfo and CINAHL) were systematically searched for eligible articles using quantitative study designs written in English, German, French, Italian, Polish, Spanish or Turkish and published from January 1, 2016 to October 27, 2022. Primary health outcomes were diagnosed psychiatric and psychological disorders, suicide (attempts), psychiatric and psychological symptoms, and perceived distress. Secondary health outcomes were more general concepts of mental health such as well-being, life satisfaction and quality of life. Screening, data extraction and the methodological quality assessment of primary studies by using the Newcastle–Ottawa Scale were done independently by two reviewers. The results of the primary studies were summarized descriptively. Migrants and refugees/asylum seekers were compared with natives in terms of the association between working conditions and mental health. Results: Migrants and refugees often face disadvantages at work concerning organizational (low-skilled work, overqualification, fixed-term contracts, shift work, lower reward levels) and social conditions (discrimination experiences) in contrast to natives. Most unfavorable working conditions are associated with worse mental health for migrants as well as for natives. Conclusions: Even if the results are to be taken with caution, it is necessary to control and improve the working conditions of migrants and refugees/asylum seekers and adapt them to those of the native population to maintain their mental health and thus their labor force.
CRIS-Team Scopus Importer:2023-09-01
Keywords: Asylum seekers; Europe; Mental health; Migrants; Refugees; Well-being

Relationship of serum beta-synuclein with blood biomarkers and brain atrophy - Oeckl, Patrick; Anderl-Straub, Sarah; Danek, Adrian; Diehl-Schmid, Janine; Fassbender, Klaus; Fliessbach, Klaus; Halbgebauer, Steffen; Huppertz, Hans Jürgen; Jahn, Holger; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, Bernhard; et al. (Alzheimers & Dementia, 2022)
Background: Recent data support beta-synuclein as a blood biomarker to study synaptic degeneration in Alzheimer's disease (AD). Methods: We provide a detailed comparison of serum beta-synuclein immunoprecipitation – mass spectrometry (IP-MS) with the established blood markers phosphorylated tau 181 (p-tau181) (Simoa) and neurofilament light (NfL) (Ella) in the German FTLD consortium cohort (n = 374) and its relation to brain atrophy (magnetic resonance imaging) and cognitive scores. Results: Serum beta-synuclein was increased in AD but not in frontotemporal lobar degeneration (FTLD) syndromes. Beta-synuclein correlated with atrophy in temporal brain structures and was associated with cognitive impairment. Serum p-tau181 showed the most specific changes in AD but the lowest correlation with structural alterations. NfL was elevated in all diseases and correlated with frontal and temporal brain atrophy. Discussion: Serum beta-synuclein changes differ from those of NfL and p-tau181 and are strongly related to AD, most likely reflecting temporal synaptic degeneration. Beta-synuclein can complement the existing panel of blood markers, thereby providing information on synaptic alterations. Highlights: Blood beta-synuclein is increased in Alzheimer's disease (AD) but not in frontotemporal lobar degeneration (FTLD) syndromes. Blood beta-synuclein correlates with temporal brain atrophy in AD. Blood beta-synuclein correlates with cognitive impairment in AD. The pattern of blood beta-synuclein changes in the investigated diseases is different to phosphorylated tau 181 (p-tau181) and neurofilament light (NfL).
CRIS-Team Scopus Importer:2022-10-07
Keywords: Alzheimer's disease; beta-synuclein; blood biomarker; brain atrophy; dementia; frontotemporal lobar degeneration; FTLD; NfL; p-tau181; synaptic degeneration

Religiosity and sense of coherence - Protective factors of mental health and well-being? - Tagay, Sefik; Erim, Yesim; Braehler, Elmar; Senf, Wolfgang (Zeitschrift für Medizinische Psychologie, 2006)
Keywords: Life satisfaction; PTSD; Mental health; Sense of coherence; Religiosity

Religiosity, Guilt, Altruism and Forgiveness in Alcohol Dependence: Results of a Cross-sectional and Prospective Cohort Study - Braun, Birgit; Weinland, Christian; Kornhuber, Johannes; Lenz, Bernd (Alcohol and Alcoholism, 2018)
Aims: To compare religious denomination, religiosity, guilt, altruism and forgiveness between alcohol-dependent patients and healthy control subjects and to prospectively investigate their relationship to the disorder's 24-month course following in-patient withdrawal treatment. Method: This study in Franconia (a mainly Christian protestant region of southern Germany) applied six questionnaires to evaluate religiosity, guilt, altruism and forgiveness in 166 alcohol-dependent in-patients during withdrawal and compared findings with that of 240 healthy controls. Results: Compared to controls religious denomination was more frequently reported by the patients (OR = 1.72, P = 0.014) and patients showed higher guilt (P < 0.001). The subjective attainability of altruism was lower in patients than in controls (P = 0.015). Higher scores on scale of inter-religious private practice predicted earlier (Rho = -0.184, P = 0.021) and more frequent alcohol-related readmissions during the follow-up (Rho = 0.207, P = 0.009). Higher religious affiliation was related to earlier (Rho = -0.214, P = 0.008) and more frequent alcohol-related readmissions (Rho = 0189, P = 0.020). Lower values of subjective attainability of altruism predicted a worse outcome (earlier [Rho = 0.231, P = 0.003] and more frequent readmissions [Rho = -0.223, P = 0.004]). The sex-specific analyses show that some of the associations are stronger in women and others are stronger in men; however, these gender differences are small and possibly biased by multiple hypothesis testing. Conclusions: We identified religious denomination, private religious practice, religious affiliation, guilt and reduced attainability of altruism as risk factors for alcohol dependence and a worse follow-up outcome. Our findings may help to establish future preventive and therapeutic strategies.
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Remember, Avert, Prevent: Franz Ludwig Berthold Kihn - A Typology of "Euthanasia" - Braun, B.; Frewer, Andreas; Kornhuber, Johannes (Fortschritte der Neurologie - Psychiatrie, 2015)
The current debate on assisted suicide provides the occasion for calling to mind the role of Berthold Kihn as a psychiatrist under National Socialism. With a historical presentation of a typology of euthanasia, the Academic Psychiatry of Erlangen together with the Medical Ethics would like to sensitize discussions on assisted suicide by drawing attention to the start and end of Kihn's scientific career.Relevant archive material, primary and secondary literature were analyzed and evaluated.As Assistant and Senior Physician at the Psychiatric and Neurological Hospital of the University of Erlangen, Kihn lectured on "the elimination of the inferiors". As Director of the Psychiatric and Neurological Hospital of Jena University, Kihn selected psychiatric patients to be murdered under the "T4 action". Kihn participated in drafting a "Euthanasia Law". Despite his involvement in the murder of mentally ill, Kihn returned to Erlangen as a "Soviet Zone refugee", where a Denazification Court considered him a "hanger-on". Kihn was reintegrated in the academic faculty of the Friedrich-Alexander-University and headed a private clinic. On 21.01.1963, the State's Attorney Nuremberg-Fuerth dropped the criminal procedure against Kihn–officially due to a lack of proof of punishable guilt.An appropriate medical historical contextualization can represent an important condition for an adequate medical ethical debate on physician-assisted suicide and the involvement of psychiatrists. FINAL COMMENT: The analysis of Kihn's patterns of thought and argumentation can help sensitize those involved in debates on physician-assisted suicide and highlights the critical role of psychiatry as a discipline in this context.
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Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels - Osborne, Lauren; Clive, Makena; Kimmel, Mary; Gispen, Fiona; Guintivano, Jerry; Brown, Tori; Cox, Olivia; Judy, Jennifer; Meilman, Samantha; Braier, Aviva; Beckmann, Matthias; Kornhuber, Johannes; et al. (Neuropsychopharmacology, 2016)
DNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood. The objective of this study was to replicate the predictive efficacy of the previously established model in women with and without a previous psychiatric diagnosis and to understand the effects of changing hormone levels on PPD biomarker loci. Using a statistical model trained on DNA methylation data from N=51 high-risk women, we prospectively predicted PPD status in an independent N=51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B, with an area under the receiver operator characteristic curve (AUC) of 0.81 (95% CI: 0.69-0.92, p<5 × 10(-4)). Modeling DNA methylation of these genes in N=240 women without a previous psychiatric diagnosis resulted in a cross-sectional prediction of PPD status with an AUC of 0.81 (95% CI: 0.68-0.93, p=0.01). TTC9B and HP1BP3 DNA methylation at early antenatal time points showed moderate evidence for association to the change in estradiol and allopregnanolone over the course of pregnancy, suggesting that epigenetic variation at these loci may be important for mediating hormonal sensitivity. In addition both loci showed PPD-specific trajectories with age, possibly mediated by age-associated hormonal changes. The data add to the growing body of evidence suggesting that PPD is mediated by differential gene expression and epigenetic sensitivity to pregnancy hormones and that modeling proxies of this sensitivity enable accurate prediction of PPD.
EVALuna2:23791

Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample - Bey, Katharina; Lennertz, Leonhard; Markett, Sebastian; Petrovsky, Nadine; Gallinat, Juergen; Gruender, Gerhard; Spreckelmeyer, Katja N.; Wienker, Thomas F.; Mobascher, Arian; Dahmen, Norbert; Thürauf, Norbert; Kornhuber, Johannes; et al. (European Neuropsychopharmacology, 2016)
Harm avoidance is a personality trait characterized by excessive worrying and fear of uncertainty, which has repeatedly been related to anxiety disorders. Converging lines of research in rodents and humans point towards an involvement of the nicotinic cholinergic system in the modulation of anxiety. Most notably, the rs1044396 polymorphism in the CHRNA4 gene, which codes for the ?4 subunit of the nicotinic acetylcholine receptor, has been linked to negative emotionality traits including harm avoidance in a recent study. Against this background, we investigated the association between harm avoidance and the rs1044396 polymorphism using data from N=1673 healthy subjects, which were collected in the context of the German multi-centre study ?Genetics of Nicotine Dependence and Neurobiological Phenotypes?. Homozygous carriers of the C-allele showed significantly higher levels of harm avoidance than homozygous T-allele carriers, with heterozygous subjects exhibiting intermediate scores. The effect was neither modulated by age or gender nor by smoking status. By replicating previous findings in a large population-based sample for the first time, the present study adds to the growing evidence suggesting an involvement of nicotinic cholinergic mechanism in anxiety and negative emotionality, which may pose an effective target for medical treatment.
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Repurposing antidepressants inhibiting the sphingomyelinase acid/ceramide system against COVID-19: current evidence and potential mechanisms - Hoertel, Nicolas; Sanchez-Rico, Marina; Cougoule, Celine; Gulbins, Erich; Kornhuber, Johannes; Carpinteiro, Alexander; Becker, Katrin Anne; Reiersen, Angela M.; Lenze, Eric J.; Seftel, David; Lemogne, Cedric; Limosin, Frederic (Molecular Psychiatry, 2021)
CRIS-Team Scopus Importer:2021-08-27

Resection of dominant fusiform gyrus is associated with decline of naming function when temporal lobe epilepsy manifests after the age of five: A voxel-based lesion-symptom mapping study - Reindl, Caroline; Allgäuer, Andrea; Kleiser, Benedict; Onugoren, Müjgan Dogan; Lang, Johannes; Welte, Tamara; Stritzelberger, Jenny; Winder, Klemens; Schwarz, Michael; Gollwitzer, Stephanie; Trollmann, Regina; Rösch, Julie; et al. (NeuroImage: Clinical, 2022)
Objective: To determine patients’ characteristics and regions in the temporal lobe where resections lead to a decline in picture naming. Methods: 311 patients with left hemispheric dominance for language were included who underwent epilepsy surgery at the Epilepsy Center of Erlangen and whose picture naming scores (Boston Naming Test, BNT) were available preoperatively and 6-months postoperatively. Surgical lesions were mapped to an averaged template based on preoperative and postoperative MRI using voxel-based lesion-symptom mapping (VBLSM). Postoperative brain shifts were corrected. The relationship between lesioned brain areas and the presence of a postoperative naming decline was examined voxel-wise while controlling for effects of overall lesion size at first in the total cohort and then restricted to temporal lobe resections. Results: In VBLSM in the total sample, a decline in BNT score was significantly related to left temporal surgery. When only considering patients with left temporal lobe resections (n = 121), 40 (33.1%) significantly worsened in BNT postoperatively. VBLSM including all patients with left temporal resections generated no significant results within the temporal lobe. However, naming decline of patients with epilepsy onset after 5 years of age was significantly associated with resections in the left inferior temporal (extent of BNT decline range: 10.8− 14.4%) and fusiform gyrus (decline range: 12.1−18.4%). Significance: Resections in the posterior part of the dominant fusiform and inferior temporal gyrus was associated with a risk of deterioration in naming performance at six months after surgery in patients with epilepsy onset after 5 years of age but not with earlier epilepsy onset.
CRIS-Team Scopus Importer:2022-08-19
Keywords: Basal temporal language area; Epilepsy surgery; Gyrus fusiformis; Lesion localization; Naming; Neuropsychological outcome

Resilience and quality of life in 161 living kidney donors before nephrectomy and in the aftermath of donation: a naturalistic single center study - Erim, Yesim; Kahraman, Yeliz; Vitinius, Frank; Beckmann, Mingo; Kroencke, Sylvia; Witzke, Oliver (BMC Nephrology, 2015)
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Resilience, Fear of Progression and Psychosocial Distress in Patients with Breast Cancer and Gynecological Tumors Seeking a Second Opinion. - Krebs, Jessica; Wasner, Sonja; Egloffstein, Sainab; Lux, Michael P.; Morawa, Eva; Beckmann, Matthias; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2018)

Resource activation and therapeutic success in in-patient and day-care psychosomatic treatment - Groß, Lisa Johanna; Stemmler, Mark; Erim, Yesim; de Zwaan, Martina (Psychotherapie Psychosomatik Medizinische Psychologie, 2015)
EVALuna:29527

Responder Analysis of a Multicomponent Non-Pharmacological Intervention (MAKS) for People With Cognitive Impairment in the German Day-Care Study (DeTaMAKS) - Luttenberger, Katharina; Grässel, Elmar; Behrndt, Elisa-Marie; Özbe, Dominik; Donath, Carolin; Scheel, Jennifer Felicia (Frontiers in Psychiatry, 2019)
Background: Multicomponent non-pharmacological therapies have been shown to be effective at reducing cognitive symptoms and slowing deterioration in abilities to perform activities of daily living (ADL) in individuals with cognitive impairment. However, little is known about response rates and predictors of response.
CRIS-Team WoS Importer:2019-09-06

Ressourcenaktivierung in der klinischen Psychologie und Psychotherapie. Überblick über theoretische Hintergründe und aktuelle Forschungsansätze - Groß, Lisa Johanna; Stemmler, Mark; Zwaan, Martina (Fortschritte der Neurologie - Psychiatrie, 2012)
Ziel des vorliegenden Artikels ist es, einen Überblick über theoretische Hintergründe und aktuelle Forschungsansätze der Ressourcenarbeit in der klinischen Psychologie und Psychotherapie zu geben. Ressourcenaktivierung gilt als wichtiger allgemeiner Wirkfaktor der Psychotherapie. Unter Ressourcenaktivierung wird im Allgemeinen ein expliziter Fokus auf die Ressourcen und Potenziale von Klienten verstanden. Nach einer Darstellung der Verwendung des Ressourcenbegriffs werden Überlegungen zur therapeutischen Haltung, Prinzipien der Ressourcenaktivierung, Ansätze zur Ressourcendiagnostik sowie unterschiedliche Forschungsansätze präsentiert. Aktuelle Forschungsarbeiten beschäftigen sich vor allem mit der Erforschung der Zusammenhänge von Ressourcenaktivierung und Prozessvariablen im Rahmen der ambulanten psychotherapeutischen Behandlung.

Results of a factor analysis of items regarding COVID-19 pandemic-specific workload among medical staff in Germany - Jerg-Bretzke, L.; Kempf, M.; Jarczok, M.; Kilian, R.; Weimer, K.; Guendel, H.; Morawa, Eva; Hiebel, N.; Schmiedgen, S.; Albus, C.; Beschoner, P. (EUROPEAN PSYCHIATRY, 2021)
CRIS-Team WoS Importer:2021-09-24

Results of a Representative Survey on the Psychosocial Evaluation Before Living Donor Kidney Transplantation in Germany - De Zwaan, Martina; Erim, Yesim; Greif-Higer, Gertrud; Kroencke, Sylvia; Burgmer, Markus; Vitinius, Frank; Kunze, Sabine; Berth, Hendrik (Psychotherapie Psychosomatik Medizinische Psychologie, 2017)
Aim Since there is no consensus about how to perform the predonation psychosocial evaluation of living kidney donor candidates, this is conducted differently in German transplant centers. Thus, the goal of the study was to learn more about how psychosocial evaluations are currently conducted in German transplant centers. Methods The psychosocial evaluators of the 38 transplant centers performing kidney transplantations in 2015 were contacted and asked to participate in an anonymous online survey. Results Psychosocial evaluators from 28 (75%) transplant centers responded. In only 30 (4%) of the evaluations contraindications for donation were reported. In most centers the psychosocial evaluation was performed after the completion of all medical tests. The evaluations were realized after only short waiting periods and were reported to be time-consuming. Financial reimbursement was mainly realized by internal cost allocation. In most centers the evaluators used semi-structured interviews. Still, there was limited consensus about structure and content of the psychosocial evaluation. Conclusion Standardization of the psychosocial evaluation process could be helpful to enable comparisons between transplant centers and to achieve equal opportunities for the potential living kidney donors and recipients.
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Results of the Voice Study: Stress and working conditions in the health system in a long-term comparison between occupational groups - Platzek, P. -S.; Jerg-Bretzke, L.; Erim, Yesim; Geiser, F.; Beschoner, P. (EUROPEAN PSYCHIATRY, 2022)
CRIS-Team WoS Importer:2023-03-17

Return to work after cancer: Improved mental health in working cancer survivors - Lieb, Marietta; Wuensch, Alexander; Schieber, Katharina; Bergelt, Corinna; Faller, Hermann; Geiser, Franziska; Goerling, Ute; Hoenig, Klaus; Hornemann, Beate; Maatouk, Imad; Niecke, Alexander; Stein, Barbara; et al. (Psycho-Oncology, 2022)
Objective Aim of the study was to compare working and non-working patients over a period of 12 months regarding socio-demographic, cancer-specific and mental health parameters. Methods This study was conducted as part of a Germany-wide longitudinal survey among 1398 patients in 13 national Comprehensive Cancer Centers. The sample used for analysis consisted of n = 430 cancer patients younger than 65 years (age M = 52.4 years, SD = 8.1; 67.0% females). Socio-demographic, cancer-specific and mental health parameters (Depression: Patient Health Questionnaire, Anxiety: Generalized Anxiety Disorder Scale, Distress: Distress Thermometer) were assessed at baseline during hospitalization and at 12 months follow-up. Results 73.7% of all patients (n = 317) have returned to work after one year. While working and non-working patients did not differ in socio-demographic parameters, there were significant differences in the presence of metastases, tumor and treatment status. Mixed analysis of variances revealed significant interactions between working status and time for depression (p = 0.009), anxiety (p = 0.003) and distress (p = 0.007). Non-working patients reported higher levels of depression, anxiety and distress than working patients over time. A logistic regression showed significant associations between lower depression (p = 0.019), lower distress (p = 0.033) and the absence of a tumor (p = 0.015) with working status. Conclusions The majority of cancer survivors returned to work. Non-working patients had higher levels of depression, anxiety and distress than working patients. After controlling for cancer-specific factors, mental health parameters were still independently associated with working status. Return to work can thus be associated with an improved mental health in cancer survivors. In order to establish causality, further research is necessary.
CRIS-Team WoS Importer:2022-01-21

Rewiring of neuronal networks during synaptic silencing - Wrosch, Jana Katharina; Von Einem, Vicky; Breininger, Katharina; Dahlmanns, Marc; Maier, Andreas; Kornhuber, Johannes; Groemer, Teja Wolfgang (Scientific Reports, 2017)
Analyzing the connectivity of neuronal networks, based on functional brain imaging data, has yielded new insight into brain circuitry, bringing functional and effective networks into the focus of interest for understanding complex neurological and psychiatric disorders. However, the analysis of network changes, based on the activity of individual neurons, is hindered by the lack of suitable meaningful and reproducible methodologies. Here, we used calcium imaging, statistical spike time analysis and a powerful classification model to reconstruct effective networks of primary rat hippocampal neurons in vitro. This method enables the calculation of network parameters, such as propagation probability, path length, and clustering behavior through the measurement of synaptic activity at the single-cell level, thus providing a fuller understanding of how changes at single synapses translate to an entire population of neurons. We demonstrate that our methodology can detect the known effects of drug-induced neuronal inactivity and can be used to investigate the extensive rewiring processes affecting population-wide connectivity patterns after periods of induced neuronal inactivity.
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Rezension: Sexualisierte Gewalt gegen Kinder: Hintergründe - Zusammenhänge - Erklärungen - Schulte, Katharina Louisa (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2023)
CRIS-Team Scopus Importer:2023-12-08

Rheumatoid vasculitis of the central nervous system - Lee, D. H.; Blinzler, C.; Stöckl, Thomas; Engelhorn, Tobias; Buslei, R.; Schwab, Sibylle; Linker, Ralf (Der Nervenarzt, 2015)
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Ribavirin with either standard or pegylated interferon to treat recurrent hepatitis C after liver transplantation - Cicinnati, Vito; Iacob, Speranta; Klein, C.G.; Baba, H.A.; Sotiropoulos, Georgios C.; Hilgard, P.; Erim, Yesim; Broelsch, Christoph E.; Gerken, Guido; Beckebaum, Susanne (Alimentary Pharmacology & Therapeutics, 2007)

Riluzole attenuates the efficacy of glutamatergic transmission by interfering with the size of the readily releasable neurotransmitter pool - Lazarevic, Vesna; Yang, Yunting; Ivanova, Daniela; Fejtová, Anna; Svenningsson, Per (Neuropharmacology, 2018)
Riluzole is a potent neuroprotective agent which primarily inhibits excitatory neurotransmission interfering with presynaptic release, uptake and postsynaptic actions of glutamate by mechanisms that are not well understood. Riluzole and related prodrugs with improved blood brain barrier penetrance, are shown to be effective for the treatment of amyotrophic lateral sclerosis, ataxias, epilepsy and mood disorders. Our study was undertaken to decipher molecular and subcellular mechanisms of riluzole's antiglutamatergic effect, particularly focusing on presynaptic active zone structure and function. Applying multifarious live cell imaging techniques and amperometric glutamate recordings, we measured the impact of riluzole on presynaptic activity, synaptic vesicle recycling and glutamate release. Our in vitro and in vivo data revealed a unique mechanism whereby riluzole reduces the efficacy of glutamatergic transmission by selectively lowering the size of the readily releasable pool. This effect was correlated with the inhibition of protein kinase C-dependent Munc18-1 phosphorylation which is known to interfere with neurotransmitter release.
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Risk of Death in Individuals Hospitalized for COVID-19 With and Without Psychiatric Disorders: An Observational Multicenter Study in France. - Hoertel, Nicolas; Sanchez-Rico, Marina; de la Muela, Pedro; Abellán, Miriam; Blanco, Carlos; Leboyer, Marion; Cougoule, Celine; Gulbins, Erich; Kornhuber, Johannes; Carpinteiro, Alexander; Becker, Katrin Anne; Vernet, Raphaël; et al. (Biological Psychiatry Global Open Science, 2023)
BACKGROUND: Prior research suggests that psychiatric disorders could be linked to increased mortality among patients with COVID-19. However, whether all or specific psychiatric disorders are intrinsic risk factors of death in COVID-19 or whether these associations reflect the greater prevalence of medical risk factors in people with psychiatric disorders has yet to be evaluated. METHODS: We performed an observational, multicenter, retrospective cohort study to examine the association between psychiatric disorders and mortality among patients hospitalized for laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals. RESULTS: Of 15,168 adult patients, 857 (5.7%) had an ICD-10 diagnosis of psychiatric disorder. Over a mean follow-up period of 14.6 days (SD = 17.9), 326 of 857 (38.0%) patients with a diagnosis of psychiatric disorder died compared with 1276 of 14,311 (8.9%) patients without such a diagnosis (odds ratio 6.27, 95% CI 5.40-7.28, p < .01). When adjusting for age, sex, hospital, current smoking status, and medications according to compassionate use or as part of a clinical trial, this association remained significant (adjusted odds ratio 3.27, 95% CI 2.78-3.85, p < .01). However, additional adjustments for obesity and number of medical conditions resulted in a nonsignificant association (adjusted odds ratio 1.02, 95% CI 0.84-1.23, p = .86). Exploratory analyses after the same adjustments suggested that a diagnosis of mood disorders was significantly associated with reduced mortality, which might be explained by the use of antidepressants. CONCLUSIONS: These findings suggest that the increased risk of COVID-19-related mortality in individuals with psychiatric disorders hospitalized for COVID-19 might be explained by the greater number of medical conditions and the higher prevalence of obesity in this population and not by the underlying psychiatric disease.
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RISK REDUCTION OF HOSPITAL ADMISSIONS FOR PEOPLE WITH DEMENTIA IN SHARED-HOUSING ARRANGEMENTS: THE DEMWG STUDY - Wolf-Ostermann, Karin; Stiefler, Susanne; Schmidt, Annika; Friedrich, Anna-Carina; Grässel, Elmar; Donath, Carolin; Scheel, Jennifer; Kratzer, André (INNOVATION IN AGING, 2022)
CRIS-Team WoS Importer:2023-03-10

Risperidone inhibits voltage-gated sodium channels - Brauner, Jan M.; Heßler, Sabine; Groemer, Teja W.; Alzheimer, Christian; Huth, Tobias (European Journal of Pharmacology, 2014)
In contrast to several other antipsychotic drugs, the effects of the atypical antipsychotic risperidone on voltage-gated sodium channels have not been characterized yet, despite its wide clinical use. Here we performed whole-cell voltage-clamp recordings to analyze the effects of risperidone on voltage-dependent sodium currents of N1E-115 mouse neuroblastoma cells carried by either endogenous sodium channels or transfected NaV1.6 channels. Risperidone inhibited both endogenous and NaV1.6-mediated sodium currents at concentrations that are expected around active synaptic release sites owing to its strong accumulation in synaptic vesicles. When determined for pharmacologically isolated NaV1.6, risperidone inhibited peak inward currents with an IC50 of 49 µM. Channel block occurred in a state-dependent fashion with risperidone displaying a fourfold higher affinity for the inactivated state than for the resting state. As a consequence of the low state dependence, risperidone produced only a small, but significant leftward shift of the steady-state inactivation curve and it required concentrations >= 30 µM to significantly slow the time course of recovery from inactivation. Risperidone (10 µM) gave rise to a pronounced use-dependent block when sodium currents were elicited by trains of brief voltage pulses at higher frequencies. Our data suggest that, compared to other antipsychotic drugs as well as to local anesthetics and sodium channel-targeting anticonvulsants, risperidone displays an unusual blocking profile where a rather low degree of state dependence is associated with a prominent use-dependent block.
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Role of Acid Sphingomyelinase in the Regulation of Social Behavior and Memory - Zoicas, Iulia; Reichel, Martin; Gulbins, Erich; Kornhuber, Johannes (PLoS ONE, 2016)
Major depressive disorder is often associated with deficits in social and cognitive functioning. Mice transgenic for acid sphingomyelinase (t-ASM) were previously shown to have a depressive-like phenotype, which could be normalized by antidepressant treatment. Here, we investigated whether t-ASM mice show deficits in social behavior and memory performance, and whether these possible deficits might be normalized by amitriptyline treatment. Our results revealed that ASM overexpression altered the behavior of mice in a sex-dependent manner. As such, t-ASM female, but not male, mice showed an impaired social preference and a depressive- and anxiogenic-like phenotype, which could be normalized by amitriptyline treatment. Both male and female t-ASM mice showed unaltered preference for social novelty, novel object recognition, and social and object discrimination abilities. Amitriptyline treatment impaired novel object recognition and object discrimination abilities in female, but not in male, wild-type mice, while female t-ASM mice showed unaltered novel object recognition and object discrimination abilities. This study suggests that female t-ASM mice represent a model of depression with comorbid anxiety and social deficits, without memory impairments. It further suggests that ASM overexpression has a protective role against the detrimental effects of amitriptyline on female, but not on male, non-social (object) memory.
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Role of hypothalamus-pituitary-adrenal axis modulation in the stress-resilient phenotype of DPP4-deficient rats - Golub, Yulia; Schildbach, Eva-Maria; Touma, Chadi; Kratz, Oliver; Moll, Gunther; von Hörsten, Stephan; Canneva, Fabio (Behavioural Brain Research, 2019)
BACKGROUND: Dipeptidyl peptidase 4 (DPP4, CD26) is a moonlighting enzyme responsible for the proteolytic inactivation of neuropeptide Y (NPY), a peptide known for its anxiolytic effect in the central nervous system. Our previous work revealed a stress-resilient phenotype and a potentiation of short-term fear extinction in a congenic rat model deficient for DPP4 activity (DPP4mut). Here, we investigated neuroendocrine mechanisms underlying the phenotype of the DPP4mut animals. We studied the function of the hypothalamus-pituitary-adrenal (HPA) axis including the expression levels of its key genes and explored the possibility of structural NPY system changes. METHODS AND RESULTS: We find decreased expression of Nr3c1 (glucocorticoid receptor - GR) and Fkbp5 (FK506 binding protein 5) in the amygdala and the hypothalamus of the DPP4mut rats, as well as the lower stress-induced peripheral corticosterone (CORT) levels. We detect no significant alterations in basal and DEX-induced CORT levels in the DPP4mut animals. The abundance of NPY-ergic neurons in the basolateral amygdala, dentate gyrus and hippocampus did not differ between the DPP4mut and their wild type littermates. CONCLUSION: DPP4mut rats show blunted CORT response in line with their lower behavioral stress-response profile. These results are consistent with the hypothesis that increased central NPY levels elevate the threshold of stress response. We suggest that changes in the expression levels of key HPA axis genes (Nr3c1 and Fkbp5) are a consequence of the altered stress-perception of DPP4mut animals, thus further contributing to the stress-resilient phenotype.
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Role of the mesolimbic dopamine system in relief learning - Mayer, Dana; Kahl, Evelyn; Uzuneser, Taygun; Fendt, Markus (Neuropsychopharmacology, 2018)
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system. The present study shows that a specific part of the mesolimbic dopamine system, the projection from the posterior medial ventral tegmental area (pmVTA) to the nucleus accumbens shell (AcbSh), is activated by aversive electric stimuli. 6-OHDA lesions of the pmVTA blocked relief learning but fear learning and safety learning were not affected. Chemogenetic silencing of the pmVTA-AcbSh projection using the DREADD approach, as well as intra-AcbSh injections of the dopamine D2/3 receptor antagonist raclopride inhibited relief learning. Taken together, the present data demonstrate that the dopaminergic pmVTA-AcbSh projection is critical for relief learning but not for similar learning phenomena. This novel finding may have clinical implications since the processing of signals predicting relief and safety is often impaired in patients suffering from anxiety disorders. Furthermore, it may help to better understand psychological conditions like non-suicidal self-injury, which are associated with pain offset relief.
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S100B, Homocysteine, Vitamin B12, Folic Acid, and Procalcitonin Serum Levels in Remitters to Electroconvulsive Therapy: A Pilot Study - Maier, Hannah; Helm, Saskia; Toto, Sermin; Moschny, Nicole; Sperling, Wolfgang; Hillemacher, Thomas; Kahl, Kai G.; Jakubovski, Ewgeni; Bleich, Stefan; Frieling, Helge; Neyazi, Alexandra (Disease Markers, 2018)
Background: Electroconvulsive therapy (ECT) is one of the most effective treatment options for refractory depressed patients. To date, there are only a few predictors of response. Aim: The aim was to identify predictive biomarkers of remission to ECT on a molecular level. Methods: 11 patients suffering from a major depressive episode-according to the Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-underwent 10 ECT sessions. Blood samples were taken, and the depression severity was assessed before, one hour and 24 hours after sessions 1, 4, 7, and 10 using the Montgomery Asberg Depression Rating Scale (MADRS). A MADRS total score < 12 was interpreted as remission. Results: Patients remitting under ECT had significantly higher homocysteine (p < 0.001), S100B (p < 0.001), and procalcitonin (PCT) (p = 0.027) serum levels. On the contrary, serum levels of vitamin B12 (p < 0.001) and folic acid (p = 0.007) were significantly lower in remitters compared to those in nonremitters. Levels remained unchanged throughout the whole ECT course. Conclusions: Our findings indicate that lower levels of vitamin B12 and folic acid associated with higher levels of homocysteine, S100B, and PCT point to a subgroup of depressed patients sensitive to ECT. Due to the limited sample size, further studies are required to replicate our findings.
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S1 guidelines "lumbar puncture and cerebrospinal fluid analysis" (abridged and translated version). - Tumani, Hayrettin; Petereit, H. F.; Gerritzen, A.; Gross, C. C.; Huss, Andre M.; Isenmann, S.; Jesse, S.; Khalil, Michael; Lewczuk, Piotr; Lewerenz, Jan; Leypoldt, Frank; Melzer, Nico; et al. (Neurological Research and Practice, 2020)
Introduction: Cerebrospinal fluid (CSF) analysis is important for detecting inflammation of the nervous system and the meninges, bleeding in the area of the subarachnoid space that may not be visualized by imaging, and the spread of malignant diseases to the CSF space. In the diagnosis and differential diagnosis of neurodegenerative diseases, the importance of CSF analysis is increasing. Measuring the opening pressure of CSF in idiopathic intracranial hypertension and at spinal tap in normal pressure hydrocephalus constitute diagnostic examination procedures with therapeutic benefits.Recommendations (most important 3-5 recommendations on a glimpse): The indications and contraindications must be checked before lumbar puncture (LP) is performed, and sampling CSF requires the consent of the patient.Puncture with an atraumatic needle is associated with a lower incidence of postpuncture discomfort. The frequency of postpuncture syndrome correlates inversely with age and body mass index, and it is more common in women and patients with a history of headache. The sharp needle is preferably used in older or obese patients, also in punctures expected to be difficult.In order to avoid repeating LP, a sufficient quantity of CSF (at least 10 ml) should be collected. The CSF sample and the serum sample taken at the same time should be sent to a specialized laboratory immediately so that the emergency and basic CSF analysis program can be carried out within 2 h.The indication for LP in anticoagulant therapy should always be decided on an individual basis. The risk of interrupting anticoagulant therapy must be weighed against the increased bleeding risk of LP with anticoagulant therapy.As a quality assurance measure in CSF analysis, it is recommended that all cytological, clinical-chemical, and microbiological findings are combined in an integrated summary report and evaluated by an expert in CSF analysis. Conclusions: In view of the importance and developments in CSF analysis, the S1 guideline "Lumbar puncture and cerebrospinal fluid analysis" was recently prepared by the German Society for CSF analysis and clinical neurochemistry (DGLN) and published in German in accordance with the guidelines of the AWMF (https://www.awmf.org). /uploads/tx_szleitlinien/030-141l_S1_Lumbalpunktion_und_Liquordiagnostik_2019-08.pdf). The present article is an abridged translation of the above cited guideline. The guideline has been jointly edited by the DGLN and DGN.
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Salivary and hair cortisol as biomarkers of emotional and behavioral symptoms in 6–9 year old children - Golub, Yulia; Kuitunen-Paul, Sören; Panaseth, Kerstin; Stonawski, Valeska; Frey, Stefan; Steigleder, Ruth; Grimm, Jennifer; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; et al. (Physiology & behavior, 2019)
The aim of the present work is to investigate the association of salivary and cumulative cortisol levels with emotional and behavioral symptoms in a Franconian Cognition and Emotion Studies (FRANCES) general population cohort of 158 6- to 9 year old children. Salivary cortisol values were measured by one-day diurnal cortisol profile, whereas cumulative cortisol was estimated via one-month hair cortisol concentrations (rHCC). Nearly all significant associations of clinical symptoms with child cortisol indices were age dependent: We report emotional symptoms being associated with lower rHCC in younger children (6.06–7.54 years). In older children (7.55–9.41 years) behavioral problems were further associated with higher rHCC and lower salivary cortisol awakening responses. In summary, child clinical symptoms were stronger associated with markers of hair cortisol compared to salivary cortisol. To picture developmental mechanisms, we suggest longitudinal designs for cortisol measures of stress systems in children and adolescents.
CRIS-Team Scopus Importer:2019-07-02
Keywords: Behavioral symptoms; Emotional symptoms; FRANCES; Hair cortisol; HPA axis; Salivary cortisol

Schizophrenia dimension-specific antipsychotic drug action and failure in amphetamine-sensitized psychotic-like rats - Uzuneser, Taygun; Schindehuette, Magnus; Dere, Ekrem; von Hörsten, Stephan; Kornhuber, Johannes; Groemer, Teja W.; Müller, Christian P. (European Neuropsychopharmacology, 2018)
Schizophrenic patients suffer from various disruptions in their psyche, mood and cognition, most of which cannot be effectively treated with the available antipsychotic drugs. Some dimensions of the schizophrenia syndrome in man can be mimicked in animals by the amphetamine (AMPH)-sensitization-induced psychosis model. Using such a sensitization procedure, we induced a psychosis-like syndrome in rats, measured as a deficit in sensory information processing and memory deficits. We then investigated the possible restorative effects of continuous treatment with haloperidol (HAL), a typical antipsychotic drug, on distinct dimensions of the syndrome. We found that, continuous infusion of a clinically relevant dose of HAL (0.5 mg/kg/day) effectively ameliorated AMPH-sensitization-induced sensorimotor gating disruptions after seven days of treatment. However, the sensory information processing deficit reappeared after prolonged HAL treatment, suggesting a treatment failure in this dimension of the syndrome. HAL had at this dose little beneficial effects on the cognitive deficits. In contrast, a continuously administered low dose of HAL (0.05 mg/kg/day) successfully attenuated cognitive deficits, but aggravated the sensorimotor gating deficit under both short- or long-term treatment conditions. Post mortem neurochemical analysis revealed that the psychotic-like behavior induced by our manipulations might be explained by altered monoamine levels in distinct brain regions. These findings provide evidence for dissociating and dose-dependent HAL treatment action and failure at different dimensions of schizophrenia.
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Schmerz bei Migranten aus der Türkei - Erim, Yesim; Glier, Barbara (Psychologische Schmerztherapie, 2011)

Screening der psychischen Gesundheit von syrischen Geflüchteten in Deutschland: Der Refugee Health Screener - Borho, Andrea; Morawa, Eva; Erim, Yesim (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2022)
Mental Health Screening of Syrian Refugees in Germany: The Refugee Health Screener 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. Methods: The RHS-15 was compared with benchmark screeners on psychological distress such as depression, anxiety, somatisation and post-traumatic stress symptoms and its diagnostic quality was assessed using appropriate methods (e. g. ROC-analyses). Results: Participants were 116 Syrian refugees (age: M = 37), 69 % of them men. The RHS-13 screened 57 % and the RHS-15 screened 66 % of participants as positive for psychological distress. Both RHS versions had very good reliability and validity and reliably identified clinically relevant psychological problems related to depression, anxiety, somatisation or PTSD. The RHS-13 proved to be more economical and slightly more valid. Conclusions: Consistent with previous findings, our results suggest that the RHS is an efficient and valid screening tool for common mental health disorders among Syrian refugees in Germany.
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Screening for caregivers at risk: Extended validation of the short version of the Burden Scale for Family Caregivers (BSFC-s) with a valid classification system for caregivers caring for an older person at home - Pendergrass, Anna; Malnis, Cintia; Graf, Uta; Engel, Sabine; Grässel, Elmar (BMC Health Services Research, 2018)
BACKGROUND: Informal caregivers' (CGs') subjective burden is an important aspect of the care situation because it is linked to various outcomes such as health, mortality risk, institutionalization, and caregiving style. The aims of this study were a) to examine the convergent and discriminant validity of the 10-item short version of the Burden Scale for Family Caregivers (BSFC-s) and b) to develop a valid classification system for interpreting BSFC-s scores. METHODS: In this cross-sectional study, we analyzed data obtained from 386 informal CGs who applied for an initial grade or upgrade of the care level for the care recipient at the Medical Service of Compulsory Health Insurance Funds of Bavaria (Germany). To validate the BSFC-s, we analyzed the reliability and the convergent/discriminant validity. We calculated correlations with the short form of the Giessen Symptom Complaints List (GBB-24), the Caregiver Strain Index (CSI), the personal further development sub-scale of the Berlin Inventory of Caregivers' Burden with Dementia Patients (BIZA-D), and other scales for establishing informal CGs' situations. To develop the classification system, we compared the percentile ranks of the GBB-24 with the respective BSFC-s sum scores and their distributions and derived three classification categories. RESULTS: Results confirmed the convergent and discriminant validity of the BSFC-s (GBB-24: r = 0.68; CSI: r = 0.70; BIZA-D: r = 0.16; p < 0.001). For informal CGs with low subjective burden, the risk of physical psychosomatic complaints was elevated to a less than average level (BSFC-s scores of 0-4). In those with a moderate subjective burden (BSFC-s scores of 5-14), the risk was elevated. In those with a high burden (BSFC-s scores of 15-30), the risk was substantially elevated. CONCLUSIONS: The BSFC-s is a valid scale for measuring subjective burden in informal CGs. The risk of physical psychosomatic complaints, which is a consequence of subjective CG burden, can be determined by using the valid classification system to deduce the necessity for action and to give concrete recommendations for interventions. The BSFC-s should therefore be employed as a screening instrument in medical contexts and in counseling services for informal CGs.
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Screening for distress in women with breast cancer diagnosed for the first time: Employment of HADS-D and PO-Bado - Erim, Yesim; Beckmann, Mingo; Gerlach, Gabriele; Kuemmel, Sherko; Oberhoff, Carsten; Senf, Wolfgang; Kimmig, Rainer (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2009)
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Keywords: Breast cancer; Psychooncology; Anxiety; Depression; Need for Psychosocial Intervention

Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: An elusive quest - Foiani, Martha S.; Cicognola, Claudia; Ermann, Natalia; Woollacott, Ione O.C.; Heller, Carolin; Heslegrave, Amanda J.; Keshavan, Ashvini; Paterson, Ross W.; Ye, Keqiang; Kornhuber, Johannes; Fox, Nick C.; Schott, Jonathan M.; et al. (Journal of Neurology Neurosurgery and Psychiatry, 2019)
Background: Frontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer's disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD. Methods: 86 participants were included: 66 with a clinical diagnosis within the FTD spectrum and 20 healthy controls. Immunoassays targeting tau fragments N-123, N-mid-region, N-224 and X-368, as well as a non-phosphorylated form of tau were measured in CSF, along with total-tau (T-tau) and phospho-tau (P-tau (181) ). Patients with FTD were grouped based on their Aβ 42 level into those likely to have underlying Alzheimer's disease (AD) pathology (n=21) and those with likely frontotemporal lobar degeneration (FTLD) pathology (n=45). The FTLD group was then subgrouped based on their underlying clinical and genetic diagnoses into those with likely tau (n=7) or TDP-43 (n=18) pathology. Results: Significantly higher concentrations of tau N-mid-region, tau N-224 and non-phosphorylated tau were seen in both the AD group and FTLD group compared with controls. However, none of the novel tau species showed a significant difference between the AD and FTLD groups, nor between the TDP-43 and tau pathology groups. In a subanalysis, normalising for total-tau, none of the novel tau species provided a higher sensitivity and specificity to distinguish between tau and TDP-43 pathology than P-tau (181) /T-tau, which itself only had a sensitivity of 61.1% and specificity of 85.7% with a cut-off of <0.109. Conclusions: Despite investigating multiple novel CSF tau fragments, none show promise as an FTD biomarker and so the quest for in vivo markers of FTLD-tau pathology continues.
CRIS-Team Scopus Importer:2019-05-02
Keywords: CSF; frontotemporal dementia; tau

Searching for success: Development of a combined patient-reported-outcome ("PRO") criterion for operationalizing success in multi-modal pain therapy - Donath, Carolin; Dorscht, Lisa; Grässel, Elmar; Sittl, Reinhard; Schoen, Christoph (BMC Health Services Research, 2015)
There is a need for a way to measure success in multi-modal pain therapy that researchers and clinicians can agree upon. According to developments in health services research, operationalizing success should take patient-reported outcomes into account. We will present a success criterion for pain therapy that combines different patient-reported variables and includes validity measures. The usable criterion should be part of a statistically significant and satisfactory model identifying predictors of successful pain therapy.Routine data from 375 patients treated with multi-modal pain therapy from 2008 to 2013 were used. The change scores of five constructs were used for the combined success criterion: pain severity, disability due to pain, depressiveness, and physical- and mental-health-related quality of life. According to the literature, an improvement of at least ½ standard deviation was required on at least four of the five constructs to count as successful. A three-step analytical approach including multiple binary logistic regression analysis was chosen to identify the predictors of therapy success with the success criterion as the dependent variable.A total of 58.1% of the patients were classified as successful. Convergent and predictive validity data show significant correlations between the criterion and established instruments, while discriminative validity could also be shown. A multiple binary logistic regression analysis confirmed the feasibility; a significant model (Chi(2) (8) = 52.585; p < .001) that explained 17.6% of the variance identified the following predictors of therapy success: highest pain severity in the last 4 weeks, disability due to pain, and number of physician visits in the last 6 months.It is possible to develop a feasible success criterion that combines several variables and includes patient-reported outcomes ("PROs") with routine data that can be used in a predictor analysis in multi-modal pain therapy. The criterion was based on basic constructs used in pain therapy and used widespread validated self-rating instruments. Thus, it should be easy to transfer this criterion to other institutions.
EVALuna2:16678

Secretion of acid Sphingomyelinase is affected by its polymorphic signal peptide - Rhein, Cosima; Reichel, Martin; Mühle, Christiane; Rotter, Andrea; Schwab, Sibylle; Kornhuber, Johannes (Cellular Physiology and Biochemistry, 2014)
Acid sphingomyelinase (ASM) catalyses the hydrolysis of sphingomyelin into ceramide, which acts as a lipid messenger that regulates important cellular functions. Deregulated ASM activity has been reported for different common diseases, but the mechanisms regulating ASM activity are still debated. ASM contains an exceptional signal peptide which is polymorphic due to a variable number of a hexanucleotide sequence that determines the length of the hydrophobic core. We investigated the impact of the signal peptide polymorphism on the regulation of ASM activity and secretion in vivo and in vitro.Subjects homozygous for the rare 4-repeat allele displayed significantly lower secreted ASM activity than subjects homozygous for the common 6-repeat allele. In vitro, overexpression of ASM variants encoded by 2, 8 or 9 repeats resulted in a significantly lowered ASM secretion rate. Treatment of ASM-overexpressing cells with tumour necrosis factor ? induced secretion of ASM, and the secretion rate was highest for the most common ASM variant encoding 6 repeats compared to other naturally occurring variants.We provide evidence that the polymorphic ASM signal peptide regulates ASM secretion. It might be an evolutionary mechanism to increase ASM secretion potential, whereas an increase in lysosomal ASM activity is limited due to deleterious cellular effects.
EVALuna2:23668

Secretory Acid Sphingomyelinase in the Serum of Medicated Patients Predicts the Prospective Course of Depression - Mühle, Christiane; Wagner, Claudia; Färber, Katharina; Richter-Schmidinger, Tanja; Gulbins, Erich; Lenz, Bernd; Kornhuber, Johannes (Journal of Clinical Medicine, 2019)
Major depressive disorder (MDD) is a highly prevalent and devastating psychiatric illness with strong individual and societal burdens. However, biomarkers to improve the limited preventive and therapeutic approaches are scarce. Multilevel evidence suggests that the pathophysiological involvement of sphingolipids particularly increases the levels of ceramides and the ceramide hydrolyzing enzyme, acid sphingomyelinase. The activity of secretory acid sphingomyelinase (S-ASM) and routine blood parameters were determined in the serum of patients with current (unmedicated n = 63, medicated n = 66) and remitted (n = 39) MDD and healthy subjects (n = 61). Depression severity and anxiety and their 3-weeks prospective course of treatment were assessed by psychometric inventories. S-ASM activity was not different between the four groups, did not decrease during treatment, and was not lower in individuals taking medication that functionally inhibited ASM. However, S-ASM correlated positively with depression severity only in remitted patients. High enzyme activity at inclusion predicted milder clinician-evaluated and self-rated depression severity (HAM-D, MADRS, BDI-II) and state anxiety at follow-up, and was related to stronger improvement in these scores in medicated patients. S-ASM was strongly and contrariwise associated with serum lipids in unmedicated and medicated females. These findings contribute to a better understanding of the pathomechanisms underlying depression and the development of clinical strategies and biomarkers.
CRIS-Team WoS Importer:2019-07-30

Secretory sphingomyelinase in health and disease - Kornhuber, Johannes; Rhein, Cosima; Müller, Christian P.; Mühle, Christiane (Biological Chemistry, 2015)
Acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, hydrolyzes sphingomyelin to ceramide and phosphorylcholine. In mammals, the expression of a single gene, SMPD1, results in two forms of the enzyme that differ in several characteristics. Lysosomal ASM (L-ASM) is located within the lysosome, requires no additional Zn2+ ions for activation and is glycosylated mainly with high-mannose oligosaccharides. By contrast, the secretory ASM (S-ASM) is located extracellularly, requires Zn2+ ions for activation, has a complex glycosylation pattern and has a longer in vivo half-life. In this review, we summarize current knowledge regarding the physiology and pathophysiology of S-ASM, including its sources and distribution, molecular and cellular mechanisms of generation and regulation and relevant in vitro and in vivo studies. Polymorphisms or mutations of SMPD1 lead to decreased S-ASM activity, as detected in patients with Niemann-Pick disease B. Thus, lower serum/plasma activities of S-ASM are trait markers. No genetic causes of increased S-ASM activity have been identified. Instead, elevated activity is the result of enhanced release (e.g., induced by lipopolysaccharide and cytokine stimulation) or increased enzyme activation (e.g., induced by oxidative stress). Increased S-ASM activity in serum or plasma is a state marker of a wide range of diseases. In particular, high S-ASM activity occurs in inflammation of the endothelium and liver. Several studies have demonstrated a correlation between S-ASM activity and mortality induced by severe inflammatory diseases. Serial measurements of S-ASM reveal prolonged activation and, therefore, the measurement of this enzyme may also provide information on past inflammatory processes. Thus, S-ASM may be both a promising clinical chemistry marker and a therapeutic target.
EVALuna2:23728

Seeing faces, when faces can't be seen: Wearing portrait photos has a positive effect on how patients perceive medical staff when face masks have to be worn - Wiesmann, Martin; Franz, Christiane; Sichtermann, Thorsten; Minkenberg, Jan; Mathern, Nathalie; Stockero, Andrea; Iordanishvili, Elene; Freiherr, Jessica; Hodson, Julian; Habel, Ute; Nikoubashman, Omid (PLoS ONE, 2021)
Introduction Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, wearing surgical face masks has become mandatory for healthcare staff in many countries when interacting with patients. Recently, it has been shown that wearing face masks impairs social interaction by diminishing a person's ability to read the emotion of their counterparts, an essential prerequisite to respond adequately in social situations. It is easily conceivable that this may have a tangible negative influence on the communication and relationship between patients and healthcare personnel. We therefore investigated whether it has an effect on how patients perceive healthcare professionals when physicians and nursing staff wear portrait photos with their smiling faces in addition to face masks. Methods During the study period of 16 days, the medical staff of our Department wore surgical face masks at all times during any kind of interaction with patients. In a pseudorandomized order, all members of our staff additionally affixed their portrait photos to their work clothes on 8 of the 16 days. After completion of their visit, 226 patients were interviewed anonymously in a cross-sectional study design using a questionnaire in which they rated the following three items: Friendliness of staff, medical quality of treatment, and how well they felt taken care of during treatment in our Department. Results On days, on which staff wore photos, mean scores of the questionnaires were significantly higher than on non-photo days (p = 0.013; mean ± standard deviation = 92.8 ± 11.3 vs. 91.0 ± 12.6; median (range) = 97 (98) vs. 96 (76)). When analyzed separately, the increased scores were only significant for the item friendliness of staff (p = 0.009; mean ± standard deviation = 95.8 ± 6.3 vs. 92.2 ± 11.5; median (range) = 98 (39) vs. 97 (54)). Conclusion Our study suggests that the use of portrait photos with smiling faces has a positive effect on how patients perceive healthcare staff.
CRIS-Team Scopus Importer:2021-06-25

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis - Kaaden, Tillman; Madlener, Marie; Angstwurm, Klemens; Bien, Christian G.; Bogarin, Yuri; Doppler, Kathrin; Finke, Alexander; Gerner, Stefan; Reimann, Gernot; Haeusler, Martin; Handreka, Robert; Hellwig, Kerstin; et al. (Neurology, Neuroimmunology and Neuroinflammation, 2022)
Background and Objectives To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD). Methods Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis. Results Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with deja-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients. Discussion Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE.
CRIS-Team WoS Importer:2022-11-11

Selection of donors for adult living-donor liver donation: Results of the assessment of the first 205 donor candidates - Erim, Yesim; Beckmann, Mingo; Valentin-Gamazo, Camino; Malago, Massimo; Frilling, Andrea; Schlaak, Joerg; Gerken, Guido; Broelsch, Christoph E.; Senf, Wolfgang (Psychosomatics, 2008)

Self-management with alcohol over lifespan: psychological mechanisms, neurobiological underpinnings, and risk assessment - Müller, Christian P.; Schumann, Gunter; Rehm, Jürgen; Kornhuber, Johannes; Lenz, Bernd (Molecular Psychiatry, 2023)
Self-management includes all behavioural measures and cognitive activities aimed at coping with challenges arising throughout the lifespan. While virtually all of these challenges can be met without pharmacological means, alcohol consumption has long been instrumentalized as a supporting tool to help coping with problems arising selectively at adolescence, adulthood, and ageing. Here, we present, to our knowledge, the first systematic review of alcohol instrumentalization throughout lifespan. We searched MEDLINE, Google Scholar, PsycINFO and CINAHL (from Jan, 1990, to Dec, 2022) and analysed consumption patterns, goals and potential neurobiological mechanisms. Evidence shows a regular non-addictive use of alcohol to self-manage developmental issues during adolescence, adulthood, and ageing. Alcohol is selectively used to overcome problems arising from dysfunctional personality traits, which manifest in adolescence. A large range of psychiatric disorders gives rise to alcohol use for the self-management of distinct symptoms starting mainly in adulthood. We identify those neuropharmacological effects of alcohol that selectively serve self-management under specific conditions. Finally, we discuss the adverse effects and associated risks that arise from the use of alcohol for self-management. Even well-controlled alcohol use adversely impacts health. Based on these findings, we suggest the implementation of an entirely new view. Health policy action may actively embrace both sides of the phenomenon through a personalized informed use that allows for harm-controlled self-management with alcohol.
CRIS-Team Scopus Importer:2023-05-05

Self-reports on symptoms of alcohol abuse: liver transplant patients versus rehabilitation therapy patients - Schieber, Katharina; Lindner, Marion; Sowa, Jan-Peter; Gerken, Guido; Scherbaum, Norbert; Kahraman, Alisan; Canbay, Ali; Erim, Yesim (Progress in Transplantation, 2015)
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Sense of coherence and depression in the framework of immigration: Turkish patients in Germany and in Turkey - Erim, Yesim; Morawa, Eva; Atay, Halil; Ayguen, Sanem; Goekalp, Peykan G.; Senf, Wolfgang (International Review of Psychiatry, 2011)

Sense of coherence and social support predict living liver donors' emotional stress prior to living-donor liver transplantation - Erim, Yesim; Beckmann, Mingo; Kroencke, Sylvia; Schulz, Karl-Heinz; Tagay, Sefik; Valentin-Gamazo, Camino; Malago, Massimo; Frilling, Andrea; Broelsch, Christoph E.; Senf, Wolfgang (Clinical Transplantation, 2008)
Keywords: coping skills; donor selection; sense of coherence; social support

Sense of coherence, social support and religiosity as resources for medical personnel during the covid-19 pandemic: A web-based survey among 4324 health care workers within the german network university medicine - Schmuck, Jonas; Hiebel, Nina; Rabe, Milena; Schneider, Juliane; Erim, Yesim; Morawa, Eva; Jerg-Bretzke, Lucia; Beschoner, Petra; Albus, Christian; Hannemann, Julian; Weidner, Kerstin; Steudte-Schmiedgen, Susann; et al. (PLoS ONE, 2021)
The COVID-19 pandemic resulted in severe detrimental effects on the mental well-being of health care workers (HCW). Consequently, there has been a need to identify health-promoting resources in order to mitigate the psychological impact of the pandemic on HCW. Objective Our objective was to investigate the association of sense of coherence (SOC), social support and religiosity with self-reported mental symptoms and increase of subjective burden during the COVID-19 pandemic in HCW. Methods Our sample comprised 4324 HCW of four professions (physicians, nurses, medical technical assistants (MTA) and pastoral workers) who completed an online survey from 20 April to 5 July 2020. Health-promoting resources were assessed using the Sense of Coherence Scale Short Form (SOC-3), the ENRICHD Social Support Inventory (ESSI) and one item on religiosity derived from the Scale of Transpersonal Trust (TPV). Anxiety and depression symptoms were measured with the PHQ-2 and GAD-2. The increase of subjective burden due to the pandemic was assessed as the retrospective difference between burden during the pandemic and before the pandemic. Results In multiple regressions, higher SOC was strongly associated with fewer anxiety and depression symptoms. Higher social support was also related to less severe mental symptoms, but with a smaller effect size, while religiosity showed minimal to no correlation with anxiety or depression. In professional group analysis, SOC was negatively associated with mental symptoms in all groups, while social support only correlated significantly with mental health outcomes in physicians and MTA. In the total sample and among subgroups, an increase of subjective burden was meaningfully associated only with a weaker SOC. Conclusion Perceived social support and especially higher SOC appeared to be beneficial for mental health of HCW during the COVID-19 pandemic. However, the different importance of the resources in the respective occupations requires further research to identify possible reasons.Copyright:
CRIS-Team Scopus Importer:2021-08-06

Serelaxin activates eNOS, suppresses inflammation, attenuates developmental delay and improves cognitive functions of neonatal rats after germinal matrix hemorrhage - Xu, Ming M.; Seyler, L.; Bäuerle, Tobias; Kalinichenko, Liubov; Müller, Christian P.; Huttner, Hagen; Schwab, Stefan; Manaenko, A. (Scientific Reports, 2020)
Germinal matrix hemorrhage (GMH) is a detrimental form of neonatal CNS injury. Following GMH-mediated eNOS inhibition, inflammation arises, contributing to GMH-induced brain injury. We investigated the beneficial effects of Serelaxin, a clinical tested recombinant Relaxin-2 protein, on brain injury after GMH in rats. We investigated whether effects of Serelaxin are mediated by its ability to activate the GMH-suppressed eNOS pathway resulting in attenuation of inflammatory marker overproduction. GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U). Seven day old Sprague–Dawley rat pups (P7) were used (n = 63). GMH animals were divided in vehicle or serelaxin treated (3 µg once, 30 µg once, 30 µg multiple, i.p., starting 30 after GMH and then daily). Sham operated animals were used. We monitored the developmental profile working memory and spatial function (T-maze and open field test respectively). At day 28, all rats underwent MRI-scans for assessment of changes in cortical thickness and white matter loss. Effects of Serelaxin on eNOS pathway activation and post-GMH inflammation were evaluated. We demonstrated that Serelaxin dose-dependently attenuated GMH-induced developmental delay, protected brain and improved cognitive functions of rats after GMH. That was associated with the decreased post-GMH inflammation, mediated at least partly by amelioration of GMH-induced eNOS inhibition.
CRIS-Team Scopus Importer:2020-05-29

Serial repetitive transcranial magnetic stimulation (rTMS) decreases BDNF serum levels in healthy male volunteers - Schaller, Gerd; Sperling, Wolfgang; Richter-Schmidinger, Tanja; Mühle, Christiane; Heberlein, Annemarie; Maihöfner, Christian; Kornhuber, Johannes; Lenz, Bernd (Journal of Neural Transmission, 2014)
Although repetitive transcranial magnetic stimulation (rTMS) is established in the treatment of depression, there is little knowledge about the underlying molecular mechanisms. In the last decade, the neurotrophic hypothesis of depression entailed a plethora of studies on the role of neurogenesis-associated factors in affective disorders and rTMS treatment. In the present study, we hypothesised a sham-controlled increase of peripheral brain-derived neurotrophic factor (BDNF) levels following serial rTMS stimulations in healthy individuals. We investigated the influence of a cycle of nine daily high-frequency (HF)-rTMS (25 Hz) stimulations over the left dorsolateral prefrontal cortex (DLPFC) on serum levels of BDNF in 44 young healthy male volunteers. BDNF serum concentrations were measured at baseline, on day 5 and on day 10. Overall, the statistical analyses showed that the active and sham group differed significantly regarding their responses of BDNF serum levels. Contrary to our expectations, there was a significant decrease of BDNF only during active treatment. Following the treatment period, significantly lower BDNF serum levels were quantified in the active group on day 10, when compared to the sham group. The participants' smoking status affected this effect. Our results suggest that serial HF-rTMS stimulations over the left DLPFC decrease serum BDNF levels in healthy male volunteers. This provides further evidence for an involvement of BDNF in clinical rTMS effects.
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SERIO - Side Effect Registry Immuno-Oncology Side Effect Registry for rare, severe and complex Side Effects of Immunotherapy - Kramer, Rafaela; Mentzer, D.; Erdmann, M.; Knauss, S.; Broeckelmann, P. J.; Hassel, J. C.; Ugurel, S.; Pavel, Marianne Ellen; Nickel, Franziska; Landendinger, M.; Fuchs, Friederike; Meidenbauer, Norbert; et al. (JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, 2020)
CRIS-Team WoS Importer:2020-09-11

Seronegative myasthenic crisis: a multicenter analysis - Mergenthaler, Philipp; Stetefeld, Henning R.; Dohmen, Christian; Kohler, Siegfried; Schoenenberger, Silvia; Boesel, Julian; Gerner, Stefan; Huttner, Hagen; Schneider, Hauke; Reichmann, Heinz; Fuhrer, Hannah; Berger, Benjamin; et al. (Journal of Neurology, 2022)
Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Seronegative patients represent around 10–15% of MG, but data on outcome of seronegative MCs are lacking. We performed a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody-positive MG (AChR-MG) or seronegative MG between 2006 and 2015 in a retrospective German multicenter study. We identified 15 seronegative MG patients with 17 MCs and 142 AChR-MG with 159 MCs. Seronegative MCs were younger (54.3 ± 14.5 vs 66.5 ± 16.3 years; p = 0.0037), had a higher rate of thymus hyperplasia (29.4% vs 3.1%; p = 0.0009), and were more likely to be female (58.8% vs 37.7%; p = 0.12) compared to AChR-MCs. Time between diagnosis of MG and MC was significantly longer in seronegative patients (8.2 ± 7.6 vs 3.1 ± 4.4 years; p < 0.0001). We found no differences in duration of mechanical ventilation (16.2 ± 15.8 vs 16.5 ± 15.9 days; p = 0.94) and length of stay at intensive care unit (17.6 ± 15.2 vs 17.8 ± 15.4 days; p = 0.96), or in-hospital mortality (11.8% vs. 10.1%; p = 0.69). We conclude that MC in seronegative MG affects younger patients after a longer period of disease, but that crisis treatment efficacy and outcome do not differ compared to AChR-MCs.
CRIS-Team Scopus Importer:2022-04-29
Keywords: Antibody status; Myasthenia gravis; Myasthenic crisis; Outcome; Seronegative

Serotonergic dysfunction in the A53T alpha-synuclein mouse model of Parkinson's disease - Deußer, Janina; Schmidt, Stefanie; Ettle, Benjamin; Ploetz, Sonja; Huber, Sabine; Müller, Christiane; Masliah, Eliezer; Winkler, Jürgen; Kohl, Zacharias (Journal of Neurochemistry, 2015)
Parkinson's disease, neuropathologically defined by the aggregation of ?-synuclein, is characterized by neuropsychiatric symptoms such as depression and anxiety preceding the onset of motor symptoms. A loss of serotonergic neurons or their projections into the hippocampus and alterations in serotonin release may be linked to these symptoms. Here, we investigate the effect of human A53T ?-synuclein on serotonergic neurons using 12-months-old transgenic mice. We detected human ?-synuclein in the perikarya of brainstem median and dorsal raphe neurons as well as in serotonergic fibers in the hippocampus. Despite intracellular ?-synuclein accumulation there was no loss of serotonergic neurons in dorsal and median raphe nuclei of A53T ?-synuclein mice. However, serotonin levels were significantly reduced in the brainstem. In addition, serotonergic fiber density in the dorsal dentate gyrus was significantly less dense in transgenic mice. Interestingly, we detected a significantly compromised increase in doublecortin+ neuroblasts after chronic treatment with fluoxetine at the site of reduced serotonergic innervation, the infrapyramidal blade of the dorsal dentate gyrus in A53T ?-synuclein mice. This suggests that ?-synuclein affects serotonergic projections in a spatially distinct pattern within the hippocampus thereby influencing the response to antidepressant treatment.
EVALuna2:23680

Serotonin and consciousness – A reappraisal - Müller, Christian P. (Behavioural Brain Research, 2022)
The serotonergic system of the brain is a major modulator of behaviour. Here we describe a re-appraisal of its function for consciousness based on anatomical, functional and pharmacological data. For a better understanding, the current model of consciousness is expanded. Two parallel streams of conscious flow are distinguished. A flow of conscious content and an affective consciousness flow. While conscious content flow has its functional equivalent in the activity of higher cortico-cortical and cortico-thalamic networks, affective conscious flow originates in segregated deeper brain structures for single emotions. It is hypothesized that single emotional networks converge on serotonergic and other modulatory transmitter neurons in the brainstem where a bound percept of an affective conscious flow is formed. This is then dispersed to cortical and thalamic networks, where it is time locked with conscious content flow at the level of these networks. Serotonin acts in concert with other modulatory systems of the brain stem with some possible specialization on single emotions. Together, these systems signal a bound percept of affective conscious flow. Dysfunctions in the serotonergic system may not only give rise to behavioural and somatic symptoms, but also essentially affect the coupling of conscious affective flow with conscious content flow, leading to the affect-stained subjective side of mental disorders like anxiety, depression, or schizophrenia. The present model is an attempt to integrate the growing insights into serotonergic system function. However, it is acknowledged, that several key claims are still at a heuristic level that need further empirical support.
CRIS-Team Scopus Importer:2022-08-05
Keywords: Affective consciousness; Conscious content; Consciousness; Flow; Serotonin

Serotonin in antipsychotic drugs action - Amato, Davide (Behavioural Brain Research, 2015)
Antipsychotic drugs are the treatment of choice in schizophrenia. Since the discovery of chlorpromazine, several generations of antipsychotic drugs have been developed with disparate mechanism of action and complex binding profile. Although the modifications of their mechanisms have translated into decreased side effects, their superior therapeutic efficacy is often debated. Furthermore, the lack of clear criteria to define antipsychotic drugs as typical or atypical is delaying the development of new compounds with innovative mechanisms of actions. There is general agreement that we are abusing dopaminergic based criteria to evaluate the newly available compounds although they are targeting several other neurotransmitter systems. The present work will overview the antipsychotic drugs effects on serotonin levels as measured with microdialysis in the rat brain. A functional association among therapeutic mechanisms of antipsychotic drugs, their serotonin receptors affinities and serotonin level changes will be attempted. The primary ambition of this investigation is to provide an exhaustive reference for who is interested, at any levels, in antipsychotic drugs effects on cortical and subcortical serotonin output.
EVALuna2:23683

Serotonin – lipid interactions and their role in behavior - Kalinichenko, Liubov; Gulbins, Erich; Kornhuber, Johannes; Müller, Christian P. (Handbook of Behavioral Neuroscience, 2020)
The dysfunction of the serotoninergic system is one of the crucial pathways for the development of psychiatric disorders such as depression, addiction, Alzheimer's and Parkinson's diseases. Many psychiatric drugs act via the interactions with serotonin receptors, transporter, or enzymes. However, current treatment strategies normalizing the functioning of serotoninergic system are characterized by low response rate, delayed effects, and substantial side effects. Thus, new treatment strategies for the modulation of brain serotonin balance are in high demand. Recent studies showed a possible involvement of the compounds of biological membrane lipids, such as cholesterol, sphingolipids, and others, in the regulation of serotonin signaling. Here, we discuss mechanisms of interaction between groups of lipids, which serve as a structural basis for membrane signaling of serotonin. Understanding these mechanisms will allow development of new strategies to indirectly target the serotoninergic system via alteration of lipid composition of membranes. This might improve therapies directed to the restoration of the serotonin balance in the brain.
CRIS-Team Scopus Importer:2020-02-04
Keywords: 5-HT; Ceramide; Cholesterol; Gangliosides; Lipid domains; Lipids; PUFAs; Serotonin; Serotonin receptors

Serotonin Signaling through Lipid Membranes - Kalinichenko, Liubov; Kornhuber, Johannes; Sinning, Steffen; Haase, Jana; Müller, Christian P. (ACS Chemical Neuroscience, 2024)
Serotonin (5-HT) is a vital modulatory neurotransmitter responsible for regulating most behaviors in the brain. An inefficient 5-HT synaptic function is often linked to various mental disorders. Primarily, membrane proteins controlling the expression and activity of 5-HT synthesis, storage, release, receptor activation, and inactivation are critical to 5-HT signaling in synaptic and extra-synaptic sites. Moreover, these signals represent information transmission across membranes. Although the lipid membrane environment is often viewed as fairly stable, emerging research suggests significant functional lipid-protein interactions with many synaptic 5-HT proteins. These protein-lipid interactions extend to almost all the primary lipid classes that form the plasma membrane. Collectively, these lipid classes and lipid-protein interactions affect 5-HT synaptic efficacy at the synapse. The highly dynamic lipid composition of synaptic membranes suggests that these lipids and their interactions with proteins may contribute to the plasticity of the 5-HT synapse. Therefore, this broader protein-lipid model of the 5-HT synapse necessitates a reconsideration of 5-HT’s role in various associated mental disorders.
CRIS-Team Scopus Importer:2024-04-12
Keywords: cholesterol; lipids; serotonin; sphingolipids; synaptic throughput

Serum acid sphingomyelinase is upregulated in chronic hepatitis C infection and non alcoholic fatty liver disease - Grammatikos, Georgios; Mühle, Christiane; Ferreiros, Nerea; Schroeter, Sirkka; Bogdanou, Dimitra; Schwalm, Stephanie; Hintereder, Gudrun; Kornhuber, Johannes; Zeuzem, Stefan; Sarrazin, Christoph; Pfeilschifter, Josef (BBA - Biochimica et Biophysica Acta, 2014)
Sphingolipids constitute bioactive molecules with functional implications in homeostasis and pathogenesis of various diseases. However, the role of sphingolipids as possible disease biomarkers in chronic liver disease remains largely unexplored. In the present study we used mass spectrometry and spectrofluorometry methods in order to quantify various sphingolipid metabolites and also assess the activity of an important corresponding regulating enzyme in the serum of 72 healthy volunteers as compared to 69 patients with non-alcoholic fatty liver disease and 69 patients with chronic hepatitis C virus infection. Our results reveal a significant upregulation of acid sphingomyelinase in the serum of patients with chronic liver disease as compared to healthy individuals (p<0.001). Especially in chronic hepatitis C infection acid sphingomyelinase activity correlated significantly with markers of hepatic injury (r=0.312, p=0.009) and showed a high discriminative power. Accumulation of various (dihydro-) ceramide species was identified in the serum of patients with non-alcoholic fatty liver disease (p<0.001) and correlated significantly to cholesterol (r=0.448, p<0.001) but showed a significant accumulation in patients with normal cholesterol values as well (p<0.001). Sphingosine, a further bioactive metabolite, was also upregulated in chronic liver disease (p<0.001). However, no significant correlation to markers of hepatic injury was identified.Chronic hepatitis C virus infection and non-alcoholic fatty liver disease induce a significant upregulation of serum acid sphingomyelinase which appears as a novel biomarker in chronic hepatopathies. Further studies are required to elucidate the potential of the sphingolipid signaling pathway as putative therapeutic target in chronic liver disease.
EVALuna2:23676

Serum lipids, leptin, and soluble leptin receptor in alcohol dependence: A cross-sectional and longitudinal study - Weinland, Christian; Tanovska, Petya; Kornhuber, Johannes; Mühle, Christiane; Lenz, Bernd (Drug and Alcohol Dependence, 2020)
Objective: Alcohol dependence affects metabolic processes. Further research is needed to apply this knowledge clinically. In this study, possible differences in serum lipids and/or leptin activities between alcohol-dependent in-patients and healthy controls and possible associations with alcohol-related blood parameters and with prospective outcomes in alcohol dependence were assessed sex-specifically.
CRIS-Team WoS Importer:2020-05-08

Serum neurofilament light chain in behavioral variant frontotemporal dementia - Steinacker, Petra; Anderl-Straub, Sarah; Diehl-Schmid, Janine; Semler, Elisa; Uttner, Ingo; Von Arnim, Christine A. F.; Barthel, Henryk; Danek, Adrian; Fassbender, Klaus; Fliessbach, Klaus; Foerstl, Hans; Grimmer, Timo; et al. (Neurology, 2018)
To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD).Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry.At baseline, serum NfL level correlated with CSF NfL (bvFTD = 0.706, < 0.0001; AD/MCI = 0.666, = 0.0003). Highest serum levels were observed in bvFTD ( <0 0.0001 vs Con and MCI, = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD ( = 0.0039 and = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] = 0.4157, = 0.0006; [follow-up] = 0.5629, < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: = -0.5857, < 0.0001; 95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] = 0.6624, < 0.0001; [follow-up] = 0.5659, = 0.0003) but not with regional brain volumes.As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials.This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.
EVALuna2:54608

Severe anorexia nervosa. Psychosomatic consultancy during acute internal medical treatment - Gerlach, Gabriele; Jochum, Christoph; Gerken, Guido; Senf, Wolfgang; Erim, Yesim (Psychotherapeut, 2012)
Keywords: Anorexia nervosa; Interdisciplinary communication; Compliance; Motivation; Psychotherapy

Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC ?-synuclein transgenic rat model of Parkinson's disease - Kohl, Zacharias; Ben Abdallah, Nada; Vogelgsang, Jonathan; Tischer, Lucas; Deußer, Janina; Amato, Davide; Anderson, Scott; Müller, Christian P.; Riess, Olaf; Masliah, Eliezer; Nuber, Silke; Winkler, Jürgen (Neurobiology of Disease, 2016)
Parkinson's disease (PD) is a multisystem disorder, involving several monoaminergic neurotransmitter systems resulting in a broad range of motor and non-motor symptoms. Pathological hallmarks of PD are the loss of dopaminergic neurons and the accumulation of alpha-synuclein, however also being present in the serotonergic raphe nuclei early in the disease course. The dysfunction of the serotonergic system projecting to the hippocampus may contribute to early non-motor symptoms such as anxiety and depression. The adult hippocampal dentate gyrus (DG), a unique niche of the forebrain continuously generating new neurons, may particularly present enhanced susceptibility towards accumulating alpha-synuclein levels. The underlying molecular mechanisms in the context of neuronal maturation and survival of new-born neurons are yet not well understood. To characterize the effects of overexpression of human full-length alpha-synuclein on hippocampal cellular and synaptic plasticity, we used a recently generated BAC alpha-synuclein transgenic rat model showing important features of PD such as widespread and progressive alpha-synuclein aggregation pathology, dopamine loss and age-dependent motor decline. At the age of four months, thus prior to the occurrence of the motor phenotype, we observed a profoundly impaired dendritogenesis of neuroblasts in the hippocampal DG resulting in severely reduced survival of adult new-born neurons. Diminished neurogenesis concurred with a serotonergic deficit in the hippocampus as defined by reduced levels of serotonin (5-HT) 1B receptor, decreased 5-HT neurotransmitter levels, and a loss of serotonergic nerve terminals innervating the DG/CA3 subfield, while the number of serotonergic neurons in the raphe nuclei remained unchanged. Moreover, alpha-synuclein overexpression reduced proteins involved in vesicle release, in particular synapsin-1 and Rab3 interacting molecule (RIM3), in conjunction with an altered ultrastructural architecture of hippocampal synapses. Importantly, BAC alpha-synuclein rats showed an early anxiety-like phenotype consisting of reduced exploratory behavior and feeding. Taken together, these findings imply that accumulating alpha-synuclein severely affects hippocampal neurogenesis paralleled by impaired 5-HT neurotransmission prior to the onset of aggregation pathology and overt motor deficits in this transgenic rat model of PD.
EVALuna2:23681

Severity assessment in maximally treated ICH patients: The max-ICH score - Sembill, Jochen; Gerner, Stefan; Volbers, Bastian; Bobinger, Tobias; Lücking, Hannes; Kloska, Stephan; Schwab, Stefan; Huttner, Hagen; Kuramatsu, Joji (Neurology, 2017)
As common prognostication models in intracerebral hemorrhage (ICH) are developed variably including patients with early (<24 hours) care limitations (ECL), we investigated its interaction with prognostication in maximally treated patients and sought to provide a new unbiased severity assessment tool.This observational cohort study analyzed consecutive ICH patients (n = 583) from a prospective registry over 5 years. We characterized the influence of ECL on overall outcome by propensity score matching and on conventional prognostication using receiver operating characteristic analyses. We established the max-ICH score based on independent predictors of 12-month functional outcome in maximally treated patients and compared it to existing models.Prevalence of ECL was 19.2% (n = 112/583) and all of these patients died. Yet propensity score matching displayed that 50.7% (n = 35/69) theoretically could have survived, with 18.8% (n = 13/69) possibly reaching favorable outcome (modified Rankin Scale score 0-3). Conventional prognostication seemed to be confounded by ECL, documented by a decreased predictive validity (area under the curve [AUC] 0.67, confidence interval [CI] 0.61-0.73 vs AUC 0.80, CI 0.76-0.83; p < 0.01), overestimating poor outcome (mortality by 44.8%, unfavorable outcome by 10.1%) in maximally treated patients. In these patients, the novel max-ICH score (0-10) integrates strength-adjusted predictors, i.e., NIH Stroke Scale score, age, intraventricular hemorrhage, anticoagulation, and ICH volume (lobar and nonlobar), demonstrating improved predictive accuracy for functional outcome (12 months: AUC 0.81, CI 0.77-0.85; p < 0.01). The max-ICH score may more accurately delineate potentials of aggressive care, showing favorable outcome in 45.4% (n = 214/471) and a long-term mortality rate of only 30.1% (n = 142/471).Care limitations significantly influenced the validity of common prognostication models resulting in overestimation of poor outcome. The max-ICH score demonstrated increased predictive validity with minimized confounding by care limitations, making it a useful tool for severity assessment in ICH patients.
EVALuna2:22564

Severity of COVID-19 disease is related to hyperactivation and altered migratory capacity of T cells - Spörl, Silvia; Kremer, Anna-Lena; Aigner, Michael; Eisenhauer, Nina; Koch, P.; Meretuk, L.; Loeffler, P.; Lutzny-Geier, Gloria; Vetter, Marcel; Bruns, Heiko; Mackensen, Andreas; Kremer, Andreas; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2021)
CRIS-Team WoS Importer:2022-03-25

Severity of Kratom (Mitragyna speciosa Korth.) Psychological Withdrawal Symptoms - Singh, Darshan; Narayanan, Suresh; Müller, Christian P.; Swogger, Marc T.; Rahim, Azlan Abdul; Bin Abdullah, Mohammad Farris Iman Leong; Vicknasingam, Balasingam K. (Journal of Psychoactive Drugs, 2018)
Kratom leaves (Mitragyna speciosa Korth.) are traditionally used in Southeast Asia for their medicinal value. Self-report studies suggest that cessation from chronic kratom tea consumption (freshly brewed kratom tea) was associated with unpleasant psychological symptoms. This study sought to assess the severity of anxiety and depression during kratom cessation. Regular kratom users (N = 150) were recruited from the northern state of Penang (Malaysia) for this retrospective study. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) scales were used to assess the severity of the symptoms of anxiety and depression. Most respondents (70%) experienced symptoms of mild anxiety, while 81% experienced symptoms of mild depression during kratom cessation. Those who consumed higher quantities of kratom tea daily (≥4 glasses) had higher odds of reporting longer duration of kratom use history (OR = 4.8, 95% CI 2.3 -10.1, p < 0.001), higher frequency of daily kratom use (≥4 times) (OR = 72, CI 9.5- 543.1, p < 0.001), and were more likely to experience moderate symptoms of depression (OR = 2.9, CI 1.1-7.3, p = 0.020) during kratom cessation than those who consumed between one and three glasses of kratom tea per day. Cessation from regular and long-term kratom tea consumption was not associated with symptoms of high anxiety or depression.
EVALuna2:211701

Sex-Dependent Alcohol Instrumentalization Goals in Non-Addicted Alcohol Consumers versus Patients with Alcohol Use Disorder: Longitudinal Change and Outcome Prediction - Müller, Christian P.; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd (Alcoholism-Clinical and Experimental Research, 2021)
Background Alcohol can be instrumentalized to achieve goals that without the drug would either not be achievable or would be so only with considerably more workload. While an understanding of the neurobiological mechanisms of alcohol instrumentalization is emerging, little information is available concerning instrumentalization goals in controlled consumers and how these goals change during the development of an alcohol use disorder (AUD).
CRIS-Team WoS Importer:2021-03-12

Sex-dependent decrease of sphingomyelinase activity during alcohol withdrawal treatment - Mühle, Christiane; Amova, Violina; Biermann, Teresa; Bayerlein, Kristina; Richter-Schmidinger, Tanja; Kraus, Thomas; Reichel, Martin; Gulbins, Erich; Kornhuber, Johannes (Cellular Physiology and Biochemistry, 2014)
Background: In vitro and in vivo studies have demonstrated the role of the acid sphingomyelinase (ASM) in pathophysiological processes and alterations in response to ethanol exposure. Cellular and plasmatic ASM activities are increased in male alcohol dependent patients and decrease during physical withdrawal. Methods: Here, we analyzed the time course of ASM in male and also female acutely intoxicated patients during alcohol withdrawal and compared the activity levels to those under long-term maintenance treatment. Craving and further psychometric parameters were assessed by questionnaires. Results: The gradual decrease of serum ASM was confirmed in males (p<0.001) and continued to lower activities in long-term patients (p=0.001). The trend was similar in females (p=0.178), although the initial enzyme activities were significantly lower (p=0.035). ASM activity strongly correlated with the body mass index in males. The initial ASM activity and its decline during the first two days were associated with the improvement in scores for the Beck depression inventory, the obsessive compulsive drinking and the withdrawal syndrome scales. Conclusion: These data support the potential of ASM as a biomarker for the course of withdrawal therapy in males and provide the first associations of this enzyme with psychological variables such as craving and depression. © 2014 S. Karger AG, Basel.
EVALuna2:23630

Sex-specific association between prenatal androgenization (second-to-fourth digit length ratio) and frontal brain volumes in adolescents - Lenz, Bernd; Gerhardt, Sarah; Boroumand-Jazi, Rafat; Eichler, Anna; Buchholz, Verena Nadine; Fasching, Peter; Kornhuber, Johannes; Banaschewski, Tobias; Flor, Herta; Guldner, Stella; Prignitz, Maren; Nees, Frauke (European archives of psychiatry and clinical neuroscience, 2022)
Prenatal androgenization associates sex-dependently with behavior and mental health in adolescence and adulthood, including risk-taking, emotionality, substance use, and depression. However, still little is known on how it affects underlying neural correlates, like frontal brain control regions. Thus, we tested whether prenatal androgen load is sex-dependently related to frontal cortex volumes in a sex-balanced adolescent sample. In a cross-sectional magnetic resonance imaging study, we examined 61 adolescents (28 males, 33 females; aged 14 or 16 years) and analyzed associations of frontal brain region volumes with the second-to-fourth digit length ratio (2D:4D), an established marker for prenatal androgenization, using voxel-based morphometry in a region-of-interest approach. Lower 2D:4D (indicative of higher prenatal androgen load) correlated significantly with smaller volumes of the right anterior cingulate cortex (r-ACC; beta = 0.45) in male adolescents and with larger volumes of the left inferior frontal gyrus orbital part (l-IFGorb; beta = - 0.38) in female adolescents. The regression slopes of 2D:4D on the r-ACC also differed significantly between males and females. The study provides novel evidence that prenatal androgenization may influence the development of the frontal brain in a sex- and frontal brain region-specific manner. These effects might contribute to the well-known sex differences in risk-taking, emotionality, substance use, and depression. Future research is needed to elucidate the role of prenatal androgenization within the biopsychosocial model.
CRIS-Team WoS Importer:2022-12-23

Sex-specific effects of different types of prenatal stress on foetal testosterone levels and NMDA expression in mice - Kalinichenko, Liubov; Smaga, Irena; Filip, Malgorzata; Lenz, Bernd; Kornhuber, Johannes; Müller, Christian P. (Behavioural Brain Research, 2023)
Prenatal stress is a critical life event often resulting in mental illnesses in the offspring. The critical developmental processes, which might trigger a cascade of molecular events resulting in mental disorders in adulthood, are still to be elucidated. Here we proposed that sex hormones, particularly testosterone, might determine the “developmental programming” of long-term consequences of prenatal stress in foetuses of both sexes. We observed that severe prenatal stress in the model of repeated corticosterone injections enhanced brain levels of corticosterone and testosterone in male foetuses. The expression of GluN1 and GluN2A, but not GluN2B NMDA receptor subunits were significantly reduced in the brain of stressed male foetuses. However, female foetuses were protected against stress effects on the brain corticosterone and testosterone levels. More moderate types of stress, such as repeated restraint stress and chronic unpredictable stress, did not induce an increase in brain corticosterone in dams and testosterone concentrations in foetuses of both sexes. Moreover, chronic unpredictable stress reduced brain testosterone concentration in male foetuses. Altogether, changes in brain testosterone level might be one of the crucial mechanisms determining the development of long-term consequences of severe prenatal stress in male, but not in female foetuses. Targeting this mechanism might allow to develop principally new prediction and therapeutic approaches for prenatal stress-associated psychiatric disorders.
CRIS-Team Scopus Importer:2022-12-16
Keywords: Developmental programming; Gender differences; NMDA; Prenatal stress; Testosterone

Sex-specific pleiotropic changes in emotional behavior and alcohol consumption in human α-synuclein A53T transgenic mice during early adulthood - Kalinichenko, Liubov; Kohl, Zacharias; Mühle, Christiane; Hassan, Zurina; Hahn, Agnes; Schmitt, Eva Maria; Macht, Kilian; Stoyanov, Lyubomir; Moghaddami-Fara, Schayan; Bilbao Canalejas, Roberto; Eulenburg, Volker; Winkler, Jürgen; et al. (Journal of neurochemistry, 2024)
Point mutations in the α-synuclein coding gene may lead to the development of Parkinson's disease (PD). PD is often accompanied by other psychiatric conditions, such as anxiety, depression, and drug use disorders, which typically emerge in adulthood. Some of these point mutations, such as SNCA and A30T, have been linked to behavioral effects that are not commonly associated with PD, especially regarding alcohol consumption patterns. In this study, we investigated whether the familial PD point mutation A53T is associated with changes in alcohol consumption behavior and emotional states at ages not yet characterized by α-synuclein accumulation. The affective and alcohol-drinking phenotypes remained unaltered in female PDGF-hA53T-synuclein-transgenic (A53T) mice during both early and late adulthood. Brain region-specific activation of ceramide-producing enzymes, acid sphingomyelinase (ASM), and neutral sphingomyelinase (NSM), known for their neuroprotective properties, was observed during early adulthood but not in late adulthood. In males, the A53T mutation was linked to a reduction in alcohol consumption in both early and late adulthood. However, male A53T mice displayed increased anxiety- and depression-like behaviors during both early and late adulthood. Enhanced ASM activity in the dorsal mesencephalon and ventral hippocampus may potentially contribute to these adverse behavioral effects of the mutation in males during late adulthood. In summary, the A53T gene mutation was associated with diverse changes in emotional states and alcohol consumption behavior long before the onset of PD, and these effects varied by sex. These alterations in behavior may be linked to changes in brain ceramide metabolism.
CRIS-Team Scopus Importer:2024-02-16
Keywords: A53T; alcohol; ceramide; depression; neutral sphingomyelinase; Parkinson's disorder

Short Communication: Interaction of Nerve Growth Factor (NGF) and Vascular Endothelial Growth Factor (VEGF) in Healthy Individuals - Groh, Adrian; Jahn, Kirsten; Groeschl, Michael; Hillemacher, Thomas; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Heberlein, Annemarie (Disease Markers, 2019)
NGF and VEGF are known to be involved in different psychiatric diseases. In order to verify hints from basic research that both neurotrophines interact with each other, serum levels of NGF and VEGF were measured in a cohort of 33 healthy individuals and correlated. NGF level was 126.30 pg/mL (+/- 155.43), and VEGF level was 57.28 pg/mL (+/- 44.48). Both factors were significantly correlated, confirming their interaction and legitimising the usage of their respective ratio (0.8 (+/- 0.42)) as a less varying additional marker in prospective studies.
CRIS-Team WoS Importer:2019-12-13

Sick Leave and Intention to Quit the Job among Nursing Staff in German Hospitals during the COVID-19 Pandemic - Schug, Caterina; Geiser, Franziska; Hiebel, Nina; Beschoner, Petra; Jerg-Bretzke, Lucia; Albus, Christian; Weidner, Kerstin; Morawa, Eva; Erim, Yesim (International Journal of Environmental Research and Public Health, 2022)
Background: Sick leave and turnover of nurses exacerbate an already existing nursing shortage during the COVID-19 pandemic in Germany and other countries. Frequency and associated factors of sick leave and intention to quit among nurses need to be examined to maintain healthcare. Methods: An online survey among nursing staff (N = 757) in German hospitals was conducted between May and July 2021. Sick leave days, intention to quit, working conditions, depression, anxiety and sleep disorder symptoms, effort-reward imbalance (ERI), COVID-19-related and sociode-mographic variables were measured. Regression analyses were performed. Results: The intention to quit was present in 18.9%. One third (32.5%) reported sick leave of ≥10 and 12.3% more than 25 days in 12 months. Significant predictors for ≥10 sick leave days were infection with SARS-CoV-2, a pre-existing illness, exhaustion, trust in colleagues and fear of becoming infected. Higher ERI reward levels, perception of sufficient staff and contact with infected patients were associated with lower odds for ≥10 sick leave days. Lower reward levels, having changed work departments during the pandemic, working part-time and higher depression levels significantly predicted turnover intention. Conclusion: Alarmingly, many nurses intend to quit working in healthcare. Perceived reward seems to buffer both sick leave and turnover intention. Enhancing protection from COVID-19 and reducing workload might also prevent sick leave. Depression prevention, improved change management and support of part-time workers could contribute to reducing turnover intention among nurses.
CRIS-Team Scopus Importer:2022-02-25
Keywords: COVID-19; Health care; Health care workers; Intention to quit; Nurses; Sick leave; Turnover

Single-center experience on liver transplantation for hepatocellular carcinoma arising in alcoholic cirrhosis: Results and ethical issues - Erim, Yesim; et al. (European Surgical Research, 2008)
Keywords: liver transplantation; hepatocellular carcinoma; alcoholic liver disease; alcoholism; recidivism; abstinence; tumor recurrence; Milan criteria; alcoholic cirrhosis

SIZE MATTERS - EXTENT OF MONOSODIUM URATE DEPOSITS BUT NOT SERUM URATE LEVEL PREDICTS COMPLETE RESOLUTION OF MONOSODIUM URATE CRYSTAL DEPOSITS IN PATIENTS WITH GOUT - Bayat, Sara; Ellmann, Hanna; Guilhon de Araujo, Elizabeth; Manger, Bernhard; Hagen, Melanie; Kleyer, Arnd; Lell, Michael; Schenker, Hannah; Simon, David; Tascilar, Koray; Baraf, Herbert S. B.; Schett, Georg; et al. (ANNALS OF THE RHEUMATIC DISEASES, 2019)
CRIS-Team WoS Importer:2019-07-12

Sleep behavior and problems in children and adolescents of a psychiatric day clinic sample: results and requirements for systematic diagnostic - Hader, Saskia; Kratz, Oliver; Eichler, Anna; Moll, Gunther; Irlbauer-Müller, Viktoria (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2021)
Sleep behavior and problems in children and adolescents of a psychiatric day clinic sample: results and requirements for systematic diagnostic Abstract. Sleep disorders are common in adults as well as children and adolescents. Children and adolescents in psychiatric treatment (CAP) are especially affected by sleep problems. Cognitive behavioral therapy represents the first-line treatment, preceded by a standardized procedure for sleep diagnostics. To date, no study has investigated sleep behavior in CAP day clinics in Germany. In this study, N = 46 children/adolescents receiving CAP treatment in a day clinic completed a sleep diary (7 days) and a sleep anamnesis scheme with the help of their parents, and their sleep behavior was assessed by a clinician. Furthermore, a parent- and a self-report questionnaire plus a clinical assessment of the mental disorders in the children/adolescents were collected. 52 % of the children/ adolescents exhibited sleep disorders or sleep abnormalities (= sleep disorder symptoms in the context of comorbid disorders), in particular problems falling asleep or to falling asleep and sleeping through the night (26 %). In addition, 33 % reported having nightmares. Their sleep behavior correlated significantly with their external behavior problems (r = .38 .61, p = .02-.04); their sex (female: p = .01-<= .001, |d| = 1.57-2.50) and their age (older: p = .05, |d| = .78) also significantly influenced sleep behavior. Particularly external behavior problems were associated with sleep problems in this day-care population. In summary, a multi-method-multi-informant procedure should be established for the systematic diagnostics of sleep abnormalities, together with individualized cognitive-behavioral therapy of sleep problems, especially in patients with external behavior problems.
CRIS-Team WoS Importer:2021-09-10

Slow cortical potential and theta/beta neurofeedback training in adults: effects on attentional processes and motor system excitability - Studer, Petra; Kratz, Oliver; Gevensleben, Holger; Rothenberger, Aribert; Moll, Gunther; Hautzinger, Martin; Heinrich, Hartmut (Frontiers in Human Neuroscience, 2014)
Neurofeedback (NF) is being successfully applied, among others, in children with attention deficit/hyperactivity disorder (ADHD) and as a peak performance training in healthy subjects. However, the neuronal mechanisms mediating a successful NF training have not yet been sufficiently uncovered for both theta/beta (T/B), and slow cortical potential (SCP) training, two protocols established in NF in ADHD. In the present, randomized, controlled investigation in adults without a clinical diagnosis (n = 59), the specificity of the effects of these two NF protocols on attentional processes and motor system excitability were to be examined, focusing on the underlying neuronal mechanisms. Neurofeedback training consisted of 10 double sessions, and self-regulation skills were analyzed. Pre- and post-training assessments encompassed performance and event-related potential measures during an attention task, and motor system excitability assessed by transcranial magnetic stimulation. Some NF protocol-specific effects have been obtained. However, due to the limited sample size medium effects did not reach the level of significance. Self-regulation abilities during negativity trials of the SCP training were associated with increased contingent negative variation amplitudes, indicating improved resource allocation during cognitive preparation. Theta/beta training was associated with increased response speed and decreased target-P3 amplitudes after successful theta/beta regulation suggested reduced attentional resources necessary for stimulus evaluation. Motor system excitability effects after theta/beta training paralleled the effects of methylphenidate. Overall, our results are limited by the non-sufficiently acquired self-regulation skills, but some specific effects between good and poor learners could be described. Future studies with larger sample sizes and sufficient acquisition of self-regulation skills are needed to further evaluate the protocol-specific effects on attention and motor system excitability reported.
EVALuna2:23874

Smartphone-based emotion recognition skills training for alexithymia - A randomized controlled pilot study - Lukas, Christian Aljoscha; Trevisi Fuentes, Hugo; Berking, Matthias (Internet Interventions, 2019)
Background: Neurobiological studies suggest that deficits in emotion recognition are common phenomena in alexithymia. Thus, effective treatments for alexithymia often include skills training in the domain of emotion recognition. Given that smartphone-based interventions (SBIs)offering skills training have been shown to be promising adjuncts to psychological treatments, a blended SBI facilitating the training of emotional skills might be effective in reducing alexithymia. Methods: In this pilot trial, N = 29 individuals reporting elevated alexithymia levels were randomly assigned to a blended SBI including a psychoeducation session and 14 days of training with the mindtastic alexithymia app (MT-ALEX)or a psychoeducation-only control condition. Primary outcome was emotion recognition skills as assessed in a computer-based two-choice task paradigm. Results: On average, participating in the SBI was associated with a significant increase in computer-assessed emotion recognition skills compared to the control condition (d = 0.97). Conclusions: Study findings provide preliminary evidence that SBIs can improve emotion recognition skills in alexithymic individuals. Research using larger samples and targeting clinical populations is necessary to further evaluate the potential of MT-ALEX.
CRIS-Team Scopus Importer:2019-05-16
Keywords: Alexithymia; Emotion recognition; Mobile intervention; Smartphone; Training

Snack food as a modulator of human resting-state functional connectivity. - Mendez Torrijos, Andrea; Kreitz, Silke; Ivan, Claudiu-Ionut; Konerth, Laura; Rösch, Julie; Pischetsrieder, Monika; Moll, Gunther; Kratz, Oliver; Dörfler, Arnd; Horndasch, Stefanie; Hess, Andreas (Cns Spectrums, 2018)
OBJECTIVE To elucidate the mechanisms of how snack foods may induce non-homeostatic food intake, we used resting state functional magnetic resonance imaging (fMRI), as resting state networks can individually adapt to experience after short time exposures. In addition, we used graph theoretical analysis together with machine learning techniques (support vector machine) to identifying biomarkers that can categorize between high-caloric (potato chips) vs. low-caloric (zucchini) food stimulation. METHODS Seventeen healthy human subjects with body mass index (BMI) 19 to 27 underwent 2 different fMRI sessions where an initial resting state scan was acquired, followed by visual presentation of different images of potato chips and zucchini. There was then a 5-minute pause to ingest food (day 1=potato chips, day 3=zucchini), followed by a second resting state scan. fMRI data were further analyzed using graph theory analysis and support vector machine techniques. RESULTS Potato chips vs. zucchini stimulation led to significant connectivity changes. The support vector machine was able to accurately categorize the 2 types of food stimuli with 100% accuracy. Visual, auditory, and somatosensory structures, as well as thalamus, insula, and basal ganglia were found to be important for food classification. After potato chips consumption, the BMI was associated with the path length and degree in nucleus accumbens, middle temporal gyrus, and thalamus. CONCLUSION The results suggest that high vs. low caloric food stimulation in healthy individuals can induce significant changes in resting state networks. These changes can be detected using graph theory measures in conjunction with support vector machine. Additionally, we found that the BMI affects the response of the nucleus accumbens when high caloric food is consume
Keywords: Food intake; graph theory; resting state networks; RS-fMRi; snack food; support vector machine

Social Fear Affects Limbic System Neuronal Activity and Gene Expression - Hamann, Catharina S.; Bankmann, Julian; Mora Maza, Hanna; Kornhuber, Johannes; Zoicas, Iulia; Schmitt-Böhrer, Angelika (International Journal of Molecular Sciences, 2022)
Social anxiety disorder (SAD) is a highly prevalent and comorbid anxiety disorder with rather unclear underlying mechanisms. Here, we aimed to characterize neurobiological changes occurring in mice expressing symptoms of social fear and to identify possible therapeutic targets for SAD. Social fear was induced via social fear conditioning (SFC), a validated animal model of SAD. We assessed the expression levels of the immediate early genes (IEGs) cFos, Fosl2 and Arc as markers of neuronal activity and the expression levels of several genes of the GABAergic, serotoninergic, oxytocinergic, vasopressinergic and neuropeptide Y (NPY)-ergic systems in brain regions involved in social behavior or fear-related behavior in SFC+ and SFC- mice 2 h after exposure to a conspecific. SFC+ mice showed a decreased number and density of cFos-positive cells and decreased expression levels of IEGs in the dorsal hippocampus. SFC+ mice also showed alterations in the expression of NPY and serotonin system-related genes in the paraventricular nucleus of the hypothalamus, basolateral amygdala, septum and dorsal raphe nucleus, but not in the dorsal hippocampus. Our results describe neuronal alterations occurring during the expression of social fear and identify the NPY and serotonergic systems as possible targets in the treatment of SAD.
CRIS-Team Scopus Importer:2022-08-12
Keywords: fear expression; gene expression; Htr1a; Htr2a; Htr2c; Npy; Npyr1; Npyr2; social anxiety; social avoidance

Social fear memory requires two stages of protein synthesis in mice - Kornhuber, Johannes; Zoicas, Iulia (International Journal of Molecular Sciences, 2020)
It is well known that long-term consolidation of newly acquired information, including information related to social fear, require de novo protein synthesis. However, the temporal dynamics of protein synthesis during the consolidation of social fear memories is unclear. To address this question, mice received a single systemic injection with the protein synthesis inhibitor, anisomycin, at different time-points before or after social fear conditioning (SFC), and memory was assessed 24 h later. We showed that anisomycin impaired the consolidation of social fear memories in a time-point-dependent manner. Mice that received anisomycin 20 min before, immediately after, 6 h, or 8 h after SFC showed reduced expression of social fear, indicating impaired social fear memory, whereas anisomycin caused no effects when administered 4 h after SFC. These results suggest that consolidation of social fear memories requires two stages of protein synthesis: (1) an initial stage starting during or immediately after SFC, and (2) a second stage starting around 6 h after SFC and lasting for at least 5 h.
CRIS-Team Scopus Importer:2020-08-14
Keywords: Anisomycin; Fear acquisition; Fear extinction; Fear learning; Fear memory; Memory consolidation; Protein synthesis; Social anxiety; Social fear; Social investigation

Social Functioning of Kratom (Mitragyna speciosa) Users in Malaysia - Singh, Darshan; Müller, Christian P.; Vicknasingam, Balasingam K.; Mansor, Sharif M. (Journal of Psychoactive Drugs, 2015)
Kratom (Mitragyna speciosa) is an indigenous plant known for its traditional medicinal use, and for its addiction potential, in Southeast Asia. In recent years, kratom and its major alkaloid, mitragynine, spread worldwide with largely unknown effects on behavior and mental health. Recent studies show that kratom use can lead to dependence and that mitragynine works as an addictive drug in animal studies. Nevertheless, kratom preparations were also suggested as a less harmful substitute in opiate withdrawal. Potential side-effects of prolonged kratom use, however, are currently unclear. The aim of this study was to investigate the social functioning of regular kratom users in Malaysia. A cross-sectional survey was carried out in three northern states of Peninsular Malaysia investigating 293 regular kratom consumers using the Addiction Severity Index in a snowball sampling technique. Findings showed that regular kratom users do not experience major impairments in their social functioning, despite being dependent on kratom for prolonged periods. Our findings suggest that chronic kratom administration does not significantly impair social functioning of users in a natural context in Malaysia.
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Social support and optimism as protective factors for mental health among 7765 healthcare workers in germany during the COVID-19 pandemic: Results of the voice study - Schug, Caterina; Morawa, Eva; Geiser, Franziska; Hiebel, Nina; Beschoner, Petra; Jerg-Bretzke, Lucia; Albus, Christian; Weidner, Kerstin; Steudte-Schmiedgen, Susann; Borho, Andrea; Lieb, Marietta; Erim, Yesim (International Journal of Environmental Research and Public Health, 2021)
Background: The COVID-19 pandemic is impacting mental health worldwide, particu-larly among healthcare workers (HCWs). Risk and protective factors for depression and generalized anxiety in healthcare workers need to be identified to protect their health and ability to work. Social support and optimism are known protective psychosocial resources, but have not been adequately studied in the context of the COVID-19 pandemic among healthcare workers in Germany. Methods: Within the first wave of the VOICE study (n = 7765), a longitudinal web-based survey study among healthcare workers in Germany, we assessed symptoms of depression (PHQ-2) and generalized anxiety (GAD-2), social support (ENRICHD Social Support Inventory; ESSI), and generalized optimism as well as sociodemographic, occupational, and COVID-19 related variables. Multiple linear regression analyses were conducted to examine associations between the constructs. Results: The analyses revealed that higher levels of social support and optimism were associated with lower levels of depression and generalized anxiety. They showed a higher association with depression and generalized anxiety than demographic or occupational risk factors such as female gender and direct contact with infected individuals. Conclusion: Psychosocial resources such as social support and optimism appear to contribute to successful coping with the COVID-19 pandemic and should be considered in future studies.
CRIS-Team Scopus Importer:2021-04-16
Keywords: Anxiety; COVID-19; Depression; Healthcare; Mental health; Optimism; Resources; Social support

Socioeconomic status and depression during and after pregnancy in the Franconian Maternal Health Evaluation Studies (FRAMES) - Hein, Alexander; Rauh, Claudia; Engel, Anne; Häberle, Lothar; Dammer, Ulf; Voigt, Franziska; Fasching, Peter; Faschingbauer, Florian; Burger, Pascal; Beckmann, Matthias; Kornhuber, Johannes; Goecke, Tamme W. (Archives of Gynecology and Obstetrics, 2014)
Depression during and after pregnancy can have a negative impact on women's quality of life and on the development of the newborn child. Interventions have been shown to have a positive influence on both mothers and children. Predictive factors for depressive symptoms might possibly be able to identify groups that are at high risk. The aim of this study was to investigate the value of socioeconomic factors in predicting depressive symptoms during and after pregnancy.Depressiveness was measured using the German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) at three time-points, in a prospective cohort study (n = 1,100). Visit 1 (Q1) was at study entry in the third trimester of the pregnancy, visit 2 (Q2) was shortly after birth, and visit 3 (Q3) was 6-8 months after birth. Depression scores were associated with socioeconomic factors and time in linear mixed models.Parity status, education status, monthly income, residential property status, and partnership status, as well as interactions between them, were found to be predictive factors for EPDS scores. The strongest factor influencing depressive symptoms was partnership status. Women who did not have an intact partnership had EPDS scores that were on average four points higher than in women with a partner at all three study visits (P < 0.000001).Socioeconomic factors define subgroups that have different depression scores during and after pregnancy. Partnership status appears to be one of the most important influencing factors and could be useful for identifying women who should be offered an intervention to prevent possible negative effects on the mother or child.
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Somatic distress among Syrian refugees with residence permission in Germany: analysis of a cross-sectional register-based study - Borho, Andrea; Morawa, Eva; Schmitt, Gregor Martin; Erim, Yesim (BMC Public Health, 2021)
Background: Previous studies have already proven high rates of common mental disorders in Syrian refugees. Nevertheless, little is known about the patterns of somatic distress among this refugee population. For this reason, we aimed to examine the prevalence, co-occurrence, and risk factors of somatic distress among Syrian refugees in Germany. Methods: This study analyzes the second measurement point (N = 116) of a prospective register-based survey among 200 adult Syrian refugees with residence permission in Germany. The survey consisted of information on sociodemographic and migration-specific characteristics, health care utilization, traumatic life events, acculturative stress (Barcelona Immigration Stress Scale (BISS); subscales: perceived discrimination, intercultural contact stress, homesickness, and general psychosocial stress), and self-reported outcomes of somatic distress (Patient Health Questionnaire (PHQ-15)), depression (PHQ-9), generalized anxiety disorder (GAD-7), and post-traumatic symptoms (Essen Trauma Inventory (ETI)). Results: Almost half of the respondents (49.1%) were identified as being at risk of somatic distress (PHQ-15 score ≥ 6), and even 24.1% being bothered by moderate-to-severe levels of somatic distress (PHQ-15 score ≥ 10). The most robust associations with somatic distress were found for female gender, the amount of health care utilization, multiple trauma exposures, general psychosocial stress, and self-reported depression and anxiety symptoms. High comorbidities with somatic distress were shown for all of the common mental disorders studied. Conclusions: The presented study reveals a significant risk of somatic distress among this displaced population and highlights implications for policy and health care providers.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Comorbidities; Germany; Health care utilization; Mental health; Somatic distress; Somatic symptoms; Syrian refugees

Somatisierung und somatoforme Störungen - Erim, Yesim; Morawa, Eva (Praxis der interkulturellen Psychiatrie und Psychotherapie: Migration und psychische Gesundheit, 2018)

Somatization among persons with Turkish origin: Results of the pretest of the German National Cohort Study - Morawa, Eva; Dragano, Nico; Jeockel, Karl-Heinz; Moebus, Susanne; Brand, Tilman; Erim, Yesim (Journal of psychosomatic research, 2017)
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Some like it, some do not: behavioral responses and central processing of olfactory-trigeminal mixture perception - Mueschenich, Franziska S.; Sichtermann, Thorsten; Di Francesco, Maria Elisa; Rodriguez-Raecke, Rea; Heim, Lennart; Singer, Marco; Wiesmann, Martin; Freiherr, Jessica (Brain Structure & Function, 2020)
Exploring the potential of eucalyptol as a masking agent for aversive odors, we found that eucalyptol masks the olfactory but not the trigeminal sensation of ammonia in a previous study. Here, we further investigate the processing of a mixture consisting of eucalyptol and ammonia, two olfactory-trigeminal stimuli. We presented the two pure odors and a mixture thereof to 33 healthy participants. The nostrils were stimulated alternately (monorhinal application). We analyzed the behavioral ratings (intensity and pleasantness) and functional brain images. First, we replicated our previous finding that, within the mixture, the eucalyptol component suppressed the olfactory intensity of the ammonia component. Second, mixture pleasantness was rated differently by participants depending on which component dominated their mixture perception. Approximately half of the volunteers rated the eucalyptol component as more intense and evaluated the mixture as pleasant (pleasant group). The other half rated the ammonia component as more intense and evaluated the mixture as unpleasant (unpleasant group). Third, these individual differences were also found in functional imaging data. Contrasting the mixture either to eucalyptol or to both single odors, neural activation was found in the unpleasant group only. Activation in the anterior insula and SII was interpreted as evidence for an attentional shift towards the potentially threatening mixture component ammonia and for trigeminal enhancement. In addition to insula and SII, further regions of the pain matrix were involved when assessing all participant responses to the mixture. Both a painful sensation and an attentional shift towards the unpleasant mixture component complicates the development of an efficient mask because a pleasant perception is an important requirement for malodor coverage.
CRIS-Team WoS Importer:2021-01-15

Somnography using unobtrusive motion sensors and Android-based mobile phones - Gradl, Stefan; Leutheuser, Heike; Kugler, Patrick; Biermann, Teresa; Kreil, Sebastian; Kornhuber, Johannes; Bergner, Matthias; Eskofier, Björn (IEEE EMBC 2013, 2013)
Sleep plays a fundamental role in the life of every human. The prevalence of sleep disorders has increased significantly, now affecting up to 50%of the general population. Sleep is usually analyzed by extracting a hypnogram containing sleep stages. The gold standard method polysomnography (PSG) requires subjects to stay overnight in a sleep laboratory and to wear a series of obtrusive devices. This work presents an easy to use method to perform somnography at home using unobtrusive motion sensors. © 2013 IEEE.

Special issue flight and migration - Erim, Yesim; Schellong, Julia (Journal of psychosomatic research, 2020)
CRIS-Team Scopus Importer:2020-10-16

Specialized neurological neurosurgical intensive care medicine - Kuramatsu, J. B.; Huttner, Hagen; Schwab, Sibylle (Der Nervenarzt, 2016)
In Germany dedicated neurological-neurosurgical critical care (NCC) is the fastest growing specialty and one of the five big disciplines integrated within the German critical care society (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin; DIVI). High-quality investigations based on resilient evidence have underlined the need for technical advances, timely optimization of therapeutic procedures, and multidisciplinary team-work to treat those critically ill patients. This evolution has repeatedly raised questions, whether NCC-units should be run independently or better be incorporated within multidisciplinary critical care units, whether treatment variations exist that impact clinical outcome, and whether nowadays NCC-units can operate cost-efficiently? Stroke is the most frequent disease entity treated on NCC-units, one of the most common causes of death in Germany leading to a great socio-economic burden due to long-term disabled patients. The main aim of NCC employs surveillance of structural and functional integrity of the central nervous system as well as the avoidance of secondary brain damage. However, clinical evaluation of these severely injured commonly sedated and mechanically ventilated patients is challenging and highlights the importance of neuromonitoring to detect secondary damaging mechanisms. This multimodal strategy not only requires medical expertise but also enforces the need for specialized teams consisting of qualified nurses, technical assistants and medical therapists. The present article reviews most recent data and tries to answer the aforementioned questions.
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Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls - Denk, Johannes; Oberhauser, Felix; Kornhuber, Johannes; Wiltfang, Jens; Fassbender, Klaus; Schroeter, Matthias L.; Volk, Alexander E.; Diehl-Schmid, Janine; Prudlo, Johannes; Danek, Adrian; Landwehrmeyer, Bernhard; Lauer, Martin; et al. (PLoS ONE, 2018)
Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer's disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results. We included several quality controls that identified and reduced technical variation to increase the reliability of our data. We showed that the expression levels of circulating miRNAs measured in CSF did not correlate with levels in serum. Using cluster analysis we found expression pattern in serum that, in part, reflects the genomic organization and affiliation to a specific miRNA family and that were specifically altered in bvFTD, AD, and control groups. Applying factor analysis we identified a 3-factor model characterized by a miRNA signature that explained 80% of the variance classifying healthy controls with 97%, bvFTD with 77% and AD with 72% accuracy. MANOVA confirmed signals like miR-320a and miR-26b-5p at BH corrected significance that contributed most to discriminate bvFTD cases with 96% sensitivity and 90% specificity and AD cases with 89% sensitivity and specificity compared to healthy controls, respectively. Correlation analysis revealed that miRNAs from the 3-factor model also correlated with levels of protein biomarker amyloid-beta1-42 and phosphorylated neurofilament heavy chain, indicating their potential role in the monitoring of progressive neuronal degeneration. Our data show that miRNAs can be reproducibly measured in serum and CSF without pre-amplification and that serum includes higher expressed signals that demonstrate an overall better ability to classify bvFTD, AD and healthy controls compared to signals detected in CSF.
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Sphingolipid control of cognitive functions in health and disease - Kalinichenko, Liubov; Gulbins, Erich; Kornhuber, Johannes; Müller, Christian P. (Progress in Lipid Research, 2022)
Cognitive processes, particularly learning and memory, are crucial brain mechanisms mediating the successful adaptation of individuals to constantly changing environmental conditions. Impairments in memory performance during neurodegenerative disorders or dementias affect life quality of patients as well as their relatives and careers, and thus have a severe socio-economic impact. The last decades have viewed learning and memory as predominantly protein-mediated process at the synapses of brain neurons. However, recent developments propose a principally new, lipid-based mechanism that regulates cognition. Thereby, crucial members of cell membranes, the sphingolipids, emerged to play an outstanding role in learning and memory. The most abundant brain sphingolipids, ceramides and gangliosides, dynamically shape the composition of protein carrying cellular membranes. This, in turn, regulates protein signaling through the membranes and overall neuronal plasticity. An imbalance in sphingolipid composition and disrupted dynamics significantly affect normal functioning of cells and results in the development of multiple psychiatric and neurological disorders with cognitive impairments. Ceramides and gangliosides interact with a plethora of molecular pathways determining de novo learning and memory, as well as pathogenic pathways of neurodegenerative disorders and dementias of various origins. Considering sphingolipids as a trigger mechanism for learning and memory under physiological and pathological conditions, a principally new class of lipid-based preventive and therapeutic approaches to target cognitive impairments and dementias is emerging.
CRIS-Team Scopus Importer:2022-04-29

Sphingolipids in Major Depression - Jernigan, Peter L.; Hoehn, Richard S.; Grassmé, Heike; Edwards, Michael J.; Müller, Christian P.; Kornhuber, Johannes; Gulbins, Erich (Neurosignals, 2015)
Major depression is one of the most common and severe diseases affecting the world's population. However, the pathogenesis of the disease remains inadequately defined. Previously, a lack of monoaminergic neurotransmitters was the focus of pathophysiological concepts; however, recent concepts focus on a alteration of neurogenesis in the hippocampus. This concept suggests that neurogenesis is decreased in major depression with a rarefication of neuronal networks and a lack of new, immature neurons in the hippocampus, events that may result in the clinical symptoms of major depression. However, molecular targets involved in the pathogenesis of major depression and, in particular, a reduction of neurogenesis, are largely unknown. We have recently discovered that an inhibition of the acid sphingomyelinase/ceramide system mediates the effects of tri- and tetracyclic antidepressants. Moreover, an accumulation of ceramide in the hippocampus results in depression-like symptoms. This suggests the acid sphingomyelinase/ceramide system is very important in the pathogenesis of major depression.
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Sphingomyelin Synthases in Neuropsychiatric Health and Disease - Mühle, Christiane; Bilbao Canalejas, Roberto; Kornhuber, Johannes (Neurosignals, 2019)
Sphingomyelin synthases (SMS) catalyze the conversion of ceramide and phosphatidylcholine to sphingomyelin and diacylglycerol and are thus crucial for the balance between synthesis and degradation of these structural and bioactive molecules. SMS thereby play an essential role in sphingolipid metabolism, cell signaling, proliferation and differentiation processes. Although tremendous progress has been made toward understanding the involvement of SMS in physiological and pathological processes, literature in the area of neuropsychiatry is still limited. In this review, we summarize the main features of SMS as well as the current methodologies and tools used for their study and provide an overview of SMS in the central nervous system and their implications in neurological as well as psychiatric disorders. This way, we aim at establishing a basis for future mechanistic as well as clinical investigations on SMS in neuropsychiatric health and diseases.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Sphingomyelin synthase; Neurological disease; Psychiatric disease; Brain; Central nervous system

Spirituality and anxiety in pastoral care workers and physicians in the first wave of the COVID-19 pandemic - Culmann, Anna C.; Baranowski, Andreas M.; Matthias, Julia K.; Tüttenberg, Simone C.; Belschner, Wilfried; Erim, Yesim; Morawa, Eva; Beschoner, Petra; Jerg-Bretzke, Lucia; Albus, Christian; Steudte-Schmiedgen, Susann; Reuter, Martin; et al. (Frontiers in Psychiatry, 2024)
Background: The COVID-19 pandemic had serious impact on the well-being of health care workers and highlighted the need for resources to help hospital staff to cope with psychologically negative consequences. The purpose of this study was to investigate the potentially protective effect of spirituality, as measured by the construct of transpersonal trust, against anxiety in physicians and in hospital pastoral care workers. In addition, transpersonal trust was compared to the effects of other potential resources, namely sense of coherence, optimism, and resilience. We also explored the relationship between transpersonal trust and anxiety and how it was moderated by sense of coherence and expected a significant effect. Method: The sample included N = 405 participants (n = 151 pastoral care workers and n = 254 physicians) who completed an online survey during the first wave of the COVID-19 pandemic between 20th April and 05th July, 2020, that comprised established questionnaires assessing anxiety, transpersonal trust, sense of coherence, and resilience. Results: There was no statistically significant negative relationship between transpersonal trust and anxiety in either profession or broken down by occupational group. Multiple regression analysis revealed that sense of coherence inversely predicted generalized anxiety, while transpersonal trust, resilience, and optimism did not. As hypothesized, the association between transpersonal trust and anxiety was moderated by sense of coherence. However, we could not confirm our hypothesis of a protective effect of transpersonal trust against anxiety. Conclusion: Our results point to the significant role of sense of coherence as a protective factor against anxiety and highlight the complexity of the relationship among spirituality, transpersonal trust, and anxiety.
CRIS-Team Scopus Importer:2024-03-29
Keywords: anxiety; generalized anxiety; protective factor; sense of coherence; spirituality; transpersonal trust

Spot quantification in two dimensional gel electrophoresis image analysis: comparison of different approaches and presentation of a novel compound fitting algorithm - Brauner, Jan M.; Groemer, Teja W.; Stroebel, Armin; Grosse-Holz, Simon; Oberstein, Timo; Wiltfang, Jens; Kornhuber, Johannes; Maler, Juan Manuel (BMC Bioinformatics, 2014)
Various computer-based methods exist for the detection and quantification of protein spots in two dimensional gel electrophoresis images. Area-based methods are commonly used for spot quantification: an area is assigned to each spot and the sum of the pixel intensities in that area, the so-called volume, is used a measure for spot signal. Other methods use the optical density, i.e. the intensity of the most intense pixel of a spot, or calculate the volume from the parameters of a fitted function.In this study we compare the performance of different spot quantification methods using synthetic and real data. We propose a ready-to-use algorithm for spot detection and quantification that uses fitting of two dimensional Gaussian function curves for the extraction of data from two dimensional gel electrophoresis (2-DE) images. The algorithm implements fitting using logical compounds and is computationally efficient. The applicability of the compound fitting algorithm was evaluated for various simulated data and compared with other quantification approaches. We provide evidence that even if an incorrect bell-shaped function is used, the fitting method is superior to other approaches, especially when spots overlap. Finally, we validated the method with experimental data of urea-based 2-DE of A? peptides andre-analyzed published data sets. Our methods showed higher precision and accuracy than other approaches when applied to exposure time series and standard gels.Compound fitting as a quantification method for 2-DE spots shows several advantages over other approaches and could be combined with various spot detection methods.The algorithm was scripted in MATLAB (Mathworks) and is available as a supplemental file.
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Stabilisation of abstinence by means of psychoeducation for patients with alcoholic liver disease awaiting liver transplantation - Erim, Yesim; Beckmann, Mingo; Tagay, Sefik; Beckebaum, Susanne; Gerken, Guido; Broelsch, Christoph E.; Senf, Wolfgang (Zeitschrift für Psychosomatische Medizin und Psychotherapie, 2006)
Keywords: transplantation; alcoholic liver disease; abstinence; compliance; psychoeducation

Standardized Evaluation of Candidates Before Liver Transplantation With the Transplant Evaluation Rating Scale - Erim, Yesim; Scheel, Jennifer; Beckmann, Mingo; Klein, Christian-Georg; Paul, Andreas (Psychosomatics, 2017)
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Statistical methods for detecting and comparing periodic data and their application to the circadian rhythm of bodily harm - Klein, Ingo; Stroebel, Armin; Bergner, Matthias; Reulbach, Udo; Biermann, Teresa; Groemer, Teja W.; Kornhuber, Johannes (Journal of Circadian Rhythms, 2010)
WiSo-Import:2015-03-26:998

Status epilepticus induces chronic silencing of burster and dominance of regular firing neurons during sharp wave-ripples in the mouse subiculum - Lippmann, Kristina; Klaft, Zin Juan; Salar, Seda; Hollnagel, Jan Oliver; Valero, Manuel; Maslarova, Anna (Neurobiology of Disease, 2022)
Sharp wave-ripples (SWRs) are hippocampal oscillations associated with memory consolidation. The subiculum, as the hippocampal output structure, ensures that hippocampal memory representations are transferred correctly to the consolidating neocortical regions. Because patients with temporal lobe epilepsy often develop memory deficits, we hypothesized that epileptic networks may disrupt subicular SWRs. We therefore investigated the impact of experimentally induced status epilepticus (SE) on subicular SWRs and contributing pyramidal neurons using electrophysiological recordings in mouse hippocampal slices. Subicular SWRs expressed hyperexcitable features post-SE, including increased ripple and unit activity. While regular firing neurons normally remain silent during SWRs, selective disinhibition recruited more regular firing neurons for action potential generation during SWRs post-SE. By contrast, burster neurons generated fewer action potential bursts during SWRs post-SE. Furthermore, altered timing of postsynaptic and action potentials suggested distorted neuronal recruitment during SWRs. Distorted subicular SWRs may therefore impair information processing and memory consolidation in epilepsy.
CRIS-Team Scopus Importer:2022-12-02
Keywords: Burster neurons; Epilepsy; Hippocampus; Memory; Regular firing neurons; Sharp wave-ripples; Status epilepticus; Subiculum

Stigmatisierung bei Adipositas - Hilbert, Anja; Ried, Jens; Zipfel, Stephan; Zwaan, Martina (Adipositas : Ursachen, Klinik, Folgeerkrankungen, 2013)

Stimmbezogene und allgemeine gesundheitsbezogene Lebensqualität kehlkopfteilresezierter Patienten - Lindl, Moritz; Haderlein, Tino; Grässel, Elmar; Maier, Andreas; Ströbele, Anika; Bohr, Christopher; Schuster, Maria (Laryngo-Rhino-Otologie, 2012)

Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma - Schumacher, Fabian; Carpinteiro, Alexander; Edwards, Michael J.; Wilson, Gregory C.; Keitsch, Simone; Soddemann, Matthias; Wilker, Barbara; Kleuser, Burkhard; Becker, Katrin Anne; Müller, Christian P.; Kornhuber, Johannes; Gulbins, Erich (Journal of Molecular Medicine, 2022)
Major depressive disorder (MDD) is a very common, severe disease with a lifetime prevalence of similar to 10%. The pathogenesis of MDD is unknown and, unfortunately, therapy is often insufficient. We have previously reported that ceramide levels are increased in the blood plasma of patients with MDD and in mice with experimental MDD. Here, we demonstrate that ceramide-enriched exosomes in the blood plasma are increased in mice with stress-induced MDD. Genetic studies reveal that neutral sphingomyelinase 2 is required for the formation of ceramide-enriched exosomes in the blood plasma. Accordingly, induced deficiency of neutral sphingomyelinase 2 prevented mice from the development of stress-induced MDD. Intravenous injection of microparticles from mice with MDD or injection of ceramide-loaded exosomes induced MDD-like behavior in untreated mice, which was abrogated by ex vivo pre-incubation of purified exosomes with anti-ceramide antibodies or ceramidase. Mechanistically, injection of exosomes from mice with MDD or injection of ex vivo ceramide-loaded microparticles inhibited phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus, which has been previously shown to mediate MDD by plasma ceramide. In summary, our data indicate that ceramide-enriched exosomes are released by neutral sphingomyelinase 2 into the blood plasma upon stress and mediate stress-induced MDD.
CRIS-Team WoS Importer:2022-09-09

Stress system dysregulation in pediatric generalized anxiety disorder associated with comorbid depression - Funke, R.; Eichler, Anna; Distler, Jörg; Golub, Yulia; Kratz, Oliver; Moll, Gunther (Stress and Health, 2016)
Because chronic stress is an important risk factor for anxiety states and depressive disorders, we studied hypothalamus-pituitary-adrenal (HPA) axis and sympathetic system activity via changes in cortisol and alpha amylase activity levels in pediatric generalized anxiety disorder (GAD) patients (n = 26) with comorbid depression and a healthy comparison group (n = 26). Morning plasma cortisol and diurnal profiles of salivary cortisol and salivary alpha amylase (sAA) activity were assessed, also reactivity of HPA-axis, sAA activity, and heart rate following a psychosocial stressor (Trier Social Stress Test for children). GAD patients with comorbid depression showed increased morning plasma and salivary cortisol levels, ameliorating throughout in-patient treatment, and higher sAA activity in their diurnal profile. Both HPA and sympathetic activity positively correlated with the severity of anxiety and depression. We also demonstrated a blunted HPA and sympathetic response to acute stress in patients. This pattern of neuroendocrine and sympathetic changes seems to be distinct from the one previously reported in pediatric patients with only social anxiety or depressive disorders. We propose morning plasma and saliva cortisol levels as potential physiological indicators for supporting the evaluation of symptoms' severity and treatment progress in children with GAD and comorbid depressive disorder.
EVALuna2:23891

Structural correlates of language processing in primary progressive aphasia - Chapman, Curtiss A.; Polyakova, Maryna; Mueller, Karsten; Weise, Christopher; Fassbender, Klaus; Fliessbach, Klaus; Kornhuber, Johannes; Lauer, Martin; Anderl-Straub, Sarah; Ludolph, Albert; Prudlo, Johannes; Staiger, Anja; et al. (Brain Communications, 2023)
Understanding the relationships between brain structure and language behaviour in primary progressive aphasia provides crucial information about these diseases' pathomechanisms. However, previous investigations have been limited from providing a statistically reliable view of broad language abilities by sample size, variant focus and task focus. In this study, the authors aimed to determine the relationship between brain structure and language behaviour in primary progressive aphasia, to determine the degree to which task-associated regions were atrophied across disease variants and to determine the degree to which task-related atrophy overlaps across disease variants. Participants were 118 primary progressive aphasia patients and 61 healthy, age-matched controls tested from 2011 to 2018 in the German Consortium for Frontotemporal Lobar Degeneration cohort. Diagnosis of primary progressive aphasia required progressive deterioration of mainly speech and language for >= 2 years, and variant was diagnosed by the criteria of Gorno-Tempini et al. (Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014). Twenty-one participants not fulfilling a specific subtype were classified as mixed-variant and excluded. Language tasks of interest included the Boston naming test, a German adaptation of the Repeat and Point task, phonemic and category fluency tasks and the reading/writing subtest of the Aachen Aphasia Test. Brain structure was measured by cortical thickness. We observed networks of language task-associated temporal, frontal and parietal cortex. Overlapping task-associated atrophy was observed in the left lateral, ventral and medial temporal lobes, middle and superior frontal gyri, supramarginal gyrus and insula. Some regions, primarily in the perisylvian region, were associated with language behaviour despite showing no significant atrophy. The results crucially extend less powerful studies associating brain and language measures in primary progressive aphasia. Cross-variant atrophy in task-associated regions suggests partially shared underlying deficits, whereas unique atrophy reinforces variant-specific deficits. Language task-related regions that are not obviously atrophied suggest regions of future network disruption and encourage understanding of task deficits beyond clearly atrophied cortex. These results may pave the way for new treatment approaches.
CRIS-Team WoS Importer:2023-05-05

Subjective and Objective Olfactory Abnormalities in Crohn's disease - Fischer, Marie; Zopf, Yurdagül; Elm, Cornelia; Pechmann, Georg; Hahn, Eckhart Georg; Schwab, Dieter; Kornhuber, Johannes; Thürauf, Norbert (Chemical Senses, 2014)
The pathogenesis of Crohn's disease (CD) is still unknown, but the involvement of the olfactory system in CD appears possible. No study to date has systematically assessed the olfactory function in CD patients. We investigated the olfactory function in CD patients in active (n = 31) and inactive disease (n = 27) and in a control group of age- and sex-matched healthy subjects (n = 35). Subjective olfactory testing was applied using the Sniffin' Sticks test. For olfactory testing, olfactory event-related potentials (OERPs) were obtained with a 4-channel olfactometer using phenyl ethyl alcohol (PEA) and hydrogen sulfide (H2S). Carbon dioxide (CO2) was employed as control stimulus, and chemosomatosensory event-related potentials (CSSERPs) were registered. Results of the Sniffin' Sticks test revealed significantly different olfactory hedonic judgment with increased olfactory hedonic estimates for pleasant odorants in CD patients in active disease compared with healthy subjects. A statistical trend was found toward lower olfactory thresholds in CD patients. In objective olfactory testing, CD patients showed lower amplitudes of OERPs and CSSERPs. Additionally, OERPs showed significantly shorter N1- and P2 latencies following stimulation of the right nostril with H2S in CD patients in inactive disease compared with controls. Our study demonstrates specific abnormalities of olfactory perception in CD patients.
EVALuna2:1836

Subjective burden of family caregivers with Turkish immigration background in Germany : Validation of the Turkish version of the Burden Scale for Family Caregivers - Ulusoy, N.; Grässel, Elmar (Zeitschrift für Gerontologie und Geriatrie, 2017)
BACKGROUND: Subjective burden is a central variable for describing the situation of family caregivers. Up to now the subjective burden of family caregivers with Turkish immigration background in Germany has not been quantitatively investigated. OBJECTIVES: The aim of this study was the validation of the Turkish version of the Burden Scale for Family Caregivers (BSFCtr). MATERIAL AND METHODS: In order to measure the subjective burden of family caregivers with Turkish immigration background, the BSFC was translated into Turkish. The internal consistency of the 28-item BSFCtrwas calculated using Cronbach's alpha. The difficulty indices and discriminating powers of the items were analyzed. The construct validity was examined by using three hypotheses of association. RESULTS: The cross-sectional study was conducted on 49 family caregivers with a Turkish immigration background in Germany who care for older, chronically ill persons. Cronbach's alpha for the total scale was 0.89. The caregiver burden was greater when the care recipient had substantial regular nursing care needs and when the spouse or partner had assumed the care as compared with the children or children-in-law. Caregiver burden significantly increased with the extent of psychosomatic symptoms of the caregiver. CONCLUSION: The Turkish version of the BSFC proved to be a reliable and valid measure for determining the subjective burden of family caregivers.
EVALuna2:33578

Subjective caregiver burden: validity of the 10-item short version of the Burden Scale for Family Caregivers BSFC-s - Grässel, Elmar; Berth, Hendrik; Lichte, Thomas; Grau, Hannes (BMC Geriatrics, 2014)
Subjective burden is a central variable describing the situation encountered by family caregivers. The 10-item short version of the Burden Scale for Family Caregivers (BSFC-short/BSFC-s) was developed to provide an economical measure of this variable. The present study examined the reliability and validity of the BSFC-s.Comprehensive data from "the IDA project" were the basis of the calculations, which included 351 dyads and examined medical data on people with dementia, interview data from their family caregivers, and health insurance data. A factor analysis was performed to explore the structure of the BSFC-s; Cronbach's alpha was used to evaluate the internal consistency of the scale. The items were analyzed to determine the item difficulty and the discriminatory power. Construct validity was tested with five hypotheses. To establish the predictive validity of the BSFC-s, predictors of institutionalization at a follow-up time of 2.5 years were analyzed (binary logistic regression).The BSFC-s score adhered to a one-factor structure. Cronbach's alpha for the complete scale was .92. A significant increase in the BSFC-s score was observed when dementia progressed, disturbing behavior occurred more frequently, care requirements increased, and when caregivers were diagnosed with depression. Caregiver burden was the second strongest predictor of institutionalization out of a total of four significant predictors.All hypotheses that referred to the construct validity were supported. The BSFC-short with its ten items is a very economical instrument for assessing the caregiver's total subjective burden in a short time frame. The BSFC-s score has predictive validity for the institutionalization of people with dementia. Therefore it is an appropriate outcome measure to evaluate caregiver interventions. The scale is available for free in 20 languages (http://www.caregiver-burden.eu). This availability facilitates the comparison of international research findings.
EVALuna2:23617

Subjective cognitive decline and rates of incident Alzheimer's disease and non-Alzheimer's disease dementia - Slot, Rosalinde E. R.; Sikkes, Sietske A. M.; Berkhof, Johannes; Brodaty, Henry; Buckley, Rachel; Cavedo, Enrica; Dardiotis, Efthimios; Guillo-Benarous, Francoise; Hampel, Harald; Kochan, Nicole A.; Lista, Simone; Luck, Tobias; et al. (Alzheimers & Dementia, 2019)
Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia.
CRIS-Team WoS Importer:2019-03-15

Subjective cognitive decline is related to CSF biomarkers of AD in patients with MCI - Wolfsgruber, Steffen; Jessen, Frank; Koppara, Alexander; Kleineidam, Luca; Schmidtke, Klaus; Froelich, Lutz; Kurz, Alexander; Schulz, Stefanie; Hampel, Harald; Heuser, Isabella; Peters, Oliver; Reischies, Friedel M.; et al. (Neurology, 2015)
To test whether, in individuals with mild cognitive impairment (MCI), different measures of subjective cognitive decline (SCD) in the memory domain predict abnormal CSF biomarkers of Alzheimer disease (AD).We analyzed the multicenter baseline (cross-sectional) data of 245 patients with MCI. SCD was measured quantitatively with the Subjective Memory Decline Scale (SMDS) and qualitatively by assessing particular concerns associated with self-experienced worsening of memory. Logistic regression models were used to examine associations between SCD and abnormal CSF biomarkers, taking into account objective memory impairment, depressive symptoms, and education as covariates.Abnormal CSF ?-amyloid 1-42 (A?42) and more depressive symptoms were associated with higher SMDS scores and with the report of memory concerns. Risk of abnormal CSF A?42 increased by an estimated 57% for a 1-SD increase in SMDS scores and was doubled in patients who had SMDS scores >4 or who reported memory concerns, respectively. In addition, both SCD measures predicted risk of having a biomarker signature indicative of prodromal AD defined as presence of low CSF A?42 together with either high CSF tau or CSF phosphorylated tau 181 levels.In MCI, specific aspects of SCD severity and quality are related to CSF biomarkers indicative of AD. This extends findings in pre-MCI samples and calls for an improved operational assessment of SCD in MCI. This might be useful for sample enrichment strategies for increased likelihood of AD pathology.
EVALuna2:23739

Subjective Distress and Depression in Relatives of People with cognitive Impairments - Long-term Results of the DeTaMAKS Study (RCT) - Donath, Carolin; Luttenberger, Katharina; Grässel, Elmar (GESUNDHEITSWESEN, 2021)
CRIS-Team WoS Importer:2022-05-20

Substrate-Dependent Inhibition of the Human Organic Cation Transporter OCT2: A Comparison of Metformin with Experimental Substrates - Hacker, Kristina; Maas, Renke; Kornhuber, Johannes; Fromm, Martin; Zolk, Oliver (PLoS ONE, 2015)
The importance of the organic cation transporter OCT2 in the renal excretion of cationic drugs raises the possibility of drug-drug interactions (DDIs) in which an inhibitor (perpetrator) drug decreases OCT2-dependent renal clearance of a victim (substrate) drug. In fact, there are clinically significant interactions for drugs that are known substrates of OCT2 such as metformin. To identify drugs as inhibitors for OCT2, individual drugs or entire drug libraries have been investigated in vitro by using experimental probe substrates such as 1-methyl-4-phenylpyridinium (MPP+) or 4-4-dimethylaminostyryl-N-methylpyridinium (ASP+). It has been questioned whether the inhibition data obtained with an experimental probe substrate such as MPP+ or ASP+ might be used to predict the inhibition against other, clinical relevant substrates such as metformin. Here we compared the OCT2 inhibition profile data for the substrates metformin, MPP+ and ASP+. We used human embryonic kidney (HEK 293) cells stably overexpressing human OCT2 as the test system to screen 125 frequently prescribed drugs as inhibitors of OCT2-mediated metformin and MPP+ uptake. Data on inhibition of OCT2-mediated ASP+ uptake were obtained from previous literature. A moderate correlation between the inhibition of OCT2-mediated MPP+, ASP+, and metformin uptake was observed (pairwise rs between 0.27 and 0.48, all P < 0.05). Of note, the correlation in the inhibition profile between structurally similar substrates such as MPP+ and ASP+ (Tanimoto similarity T = 0.28) was even lower (rs = 0.27) than the correlation between structurally distinct substrates, such as ASP+ and metformin (T = 0.01; rs = 0.48) or MPP+ and metformin (T = 0.01; rs = 0.40). We identified selective as well as universal OCT2 inhibitors, which inhibited transport by more than 50% of one substrate only or of all substrates, respectively. Our data suggest that the predictive value for drug-drug interactions using experimental substrates rather than the specific victim drug is limited.
EVALuna2:8691

Successful Pharmacologic Treatment of Self-Bloodletting with Factitious Chronic Anemia (Lasthénie de Ferjol Syndrome) with High-Dose Serotonergic Medication: A Case Report - Mestermann, Stefan; Rudtke, Laura; Brazdis, Razvan Marius; Tsaktanis, Thanos; Kornhuber, Johannes; Thürauf, Norbert (Behavioral Sciences, 2024)
Self-induced bloodletting (SBL) is a very rare form of self-injury (SI) seen primarily in adolescents and young adults with personality and eating disorders. It can result in complications like malaise, fatigue, or iron-deficiency anemia (Lasthénie de Ferjol syndrome, LFS), and poses a risk of accidental death or suicide. The condition often goes undetected due to patient concealment. There is no specific treatment established, and pharmacological strategies remain uncertain. We discuss the case of a 22-year-old female patient treated at our Psychiatry and Psychotherapy Department following a suicide attempt via SBL. She self-administered a venous cannula, losing 1.5 L of blood. Diagnosed with iron-deficiency anemia (LFS), she was initially treated with mirtazapine, risperidone, lithium, and later off-label high-dose clomipramine (300 mg/d). Clomipramine significantly reduced her SBL and suicidal thoughts, and her hemoglobin levels re-normalized under iron-substitution therapy. Despite improvement and later discharge, she attempted suicide by SBL again three months later, having stopped clomipramine due to adverse side effects. High-dose escitalopram was administered, leading to a decrease and eventual cessation of her SBL urges. This case demonstrates that patients with SBL/LFS can benefit from high-dose clomipramine or escitalopram. Despite its rarity, the consideration of high-dose serotonergic antidepressants is crucial in psychiatric diagnostics and treatment for patients affected by SBL/LFS.
CRIS-Team Scopus Importer:2024-04-05
Keywords: clomipramine; escitalopram; Lasthénie de Ferjol syndrome; mental health; self-bloodletting; self-harm; self-injury behavior

SUCLG2 identified as both a determinator of CSF A?1-42 levels and an attenuator of cognitive decline in Alzheimer's disease - Ramirez, Alfredo; Van Der Flier, Wiesje M.; Herold, Christine; Ramonet, David; Heilmann, Stefanie; Lewczuk, Piotr; Popp, Julius; Lacour, Andre; Drichel, Dmitriy; Louwersheimer, Eva; Kummer, Markus P.; Cruchaga, Carlos; et al. (Human Molecular Genetics, 2014)
Cerebrospinal fluid amyloid-beta 1-42 (A?1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on A?1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between A?1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-?4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of A?1-42.
EVALuna2:23657

Sulphated dehydroepiandrosterone serum levels are reduced in women with alcohol use disorder and correlate negatively with craving: A sex-separated cross-sectional and longitudinal study - Weinland, Christian; Mühle, Christiane; von Zimmermann, Claudia; Kornhuber, Johannes; Lenz, Bernd (Addiction Biology, 2022)
Previous studies have established a role of sex hormones in alcohol use disorder (AUD).Only few clinical investigations with low numbers of patients with AUD have focused on the sulphated form of dehydroepiandrosterone (DHEA-S), despite its function as a neuromodulating sex steroid on receptors in the central nervous system (γ-aminobutyric acid type A, N-methyl-D-aspartate, sigma-1 receptors). DHEA-S serum levels were compared between 200 inpatients with AUD (44% women) admitted for withdrawal treatment and 240 healthy controls (45% women) and analysed longitudinally in patients from early abstinence (baseline) to a median of 5 days later. We also correlated DHEA-S levels with craving, liver enzyme activities, and prospective alcohol-related readmissions during a 24-month follow-up. DHEA-S concentrations were lower in female patients than in female healthy controls during baseline (70%) and decreased from baseline to follow-up in the female and male patients groups (down to: women, 92%; men, 76%). Baseline DHEA-S concentrations correlated with the total and obsessive subscales of the Obsessive–Compulsive Drinking Scale and with maximum visual analogue scale craving scores in female patients (Rho ≤ −0.240) and gamma-glutamyl transferase activity in female (Rho = −0.292) and male (Rho = −0.391) patients. DHEA-S did not significantly predict outcome. We found interactions with smoking behaviour and age. This is the first study based on large cohorts of inpatients with AUD undergoing a qualified detoxification treatment to provide sex-separated evidence for associations of DHEA-S serum concentrations with AUD and related phenotypes. The results stimulate further investigations whether DHEA-S directly influences alcohol craving building a basis to develop sex-sensitive prevention and treatment strategies.
CRIS-Team Scopus Importer:2022-03-11
Keywords: AUD; craving; DHEA -S; relapse; sex hormones

Surface Trafficking of APP and BACE in Live Cells - Bauereiß, Anna; Welzel, Oliver; Jung, Jasmin; Grosse-Holz, Simon; Lelental, Natalia; Lewczuk, Piotr; Wenzel, Eva M.; Kornhuber, Johannes; Groemer, Teja W. (Traffic, 2015)
Amyloid-? (A?)-peptide, the major constituent of the plaques that develop during Alzheimer's disease, is generated via the cleavage of A? precursor protein (APP) by ?-site APP-cleaving enzyme (BACE). Using live-cell imaging of APP and BACE labeled with pH-sensitive proteins, we could detect the release events of APP and BACE and their distinct kinetics. We provide kinetic evidence for the cleavage of APP by ?-secretase on the cellular surface after exocytosis. Furthermore, simultaneous dual-color evanescent field illumination revealed that the two proteins are trafficked to the surface in separate compartments. Perturbing the membrane lipid composition resulted in a reduced frequency of exocytosis and affected BACE more strongly than APP. We propose that surface fusion frequency is a key factor regulating the aggregation of APP and BACE in the same membrane compartment and that this process can be modulated via pharmacological intervention.
EVALuna2:23697

Surgical hematoma evacuation of cortical intracerebral hemorrhage ≥10 ml reduces risk of subsequent epilepsy by more than 70%: A retrospective monocenter study - Welte, Tamara; Steidl, Josephine; Stritzelberger, Jenny; Gollwitzer, Stephanie; Lang, Johannes; Reindl, Caroline; Rampp, Stefan; Maslarova, Anna; Brandner, Sebastian; Hock, Stefan; Mühlen, Iris; Dörfler, Arnd; et al. (European Journal of Neurology, 2022)
Aim: The aim of this study was to re-evaluate risk factors for post-ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH. Background and purpose: Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain. Methods: We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni- and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation. Results: Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow-up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025). Conclusions: Post-ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH.
CRIS-Team Scopus Importer:2022-10-21
Keywords: CAVE score; hematoma evacuation; intracerebral hemorrhage; post-stroke epilepsy

Surgical planning, histopathology findings and postoperative outcome in MR-negative extra-temporal epilepsy using intracranial EEG, functional imaging, magnetoencephalography, neuronavigation and intraoperative MRI. - Maslarova, Anna; Zhao, Yining; Rösch, Julie; Dörfler, Arnd; Coras, Roland; Blümcke, Ingmar; Lang, Johannes; Schmidt, Manuel; Hamer, Hajo; Reindl, Caroline; Welte, Tamara; Rampp, Stefan; et al. (Clinical Neurology and Neurosurgery, 2023)
OBJECTIVE: MRI-negative drug-resistant epilepsy presents a challenge when it comes to surgical planning, and surgical outcome is worse than in cases with an identified lesion. Although increasing implementation of more powerful MRI scanners and artificial intelligence has led to the detection of previously unrecognizable lesions, in some cases even postoperative pathological evaluation of electrographically epileptogenic zones shows no structural alterations. While in temporal lobe epilepsy a standardized resection approach can usually be performed, the surgical management of extra-temporal lesions is always individual. Here we present a strategy for treating patients with extra-temporal MRI-negative epilepsy focus and report our histological findings and patient outcome. METHODS: Patients undergoing epilepsy surgery in the Department of Neurosurgery at the University Hospital Erlangen between 2012 and 2020 were included in the study. Inclusion criteria were: (1) failure to identify a structural lesion on preoperative high-resolution 3 Tesla MRI with a standardized epilepsy protocol and (2) preoperative intracranial EEG (iEEG) diagnostics. RESULTS: We identified 8 patients corresponding to the inclusion criteria. Second look MRI analysis by an experienced neuroradiologist including the most recent analysis algorithm utilized in our clinic revealed a possible lesion in two patients. One of the patients with a clear focal cortical dysplasia (FCD) finding on a second look was excluded from further analysis. Of the other 7 patients, in one patient iEEG was performed with subdural electrodes, whereas the other 6 were evaluated with depth electrodes. MEG was performed preoperatively in all but one patient. An MEG focus was implemented in resection planning in 3 patients. FDG PET was performed in all, but only implemented in one patient. Histopathological evaluation revealed one non-lesional case, 4 cases of FCD and 2 cases with mild developmental malformation. All patients were free from permanent neurological deficits and presented with Engel 1A or 1B outcome on the last follow-up. CONCLUSION: We demonstrate that extra-temporal MRI-negative epilepsy can be treated successfully provided an extensive preoperative planning is performed. The most important diagnostic was stereo-EEG, whereas additional data from MEG was helpful and FDG PET was rarely useful in our cohort.
EVALuna2:522951

Sustained effects of neurofeedback in ADHD: a systematic review and meta-analysis - Van Doren, Jessica; Arns, Martijn; Heinrich, Hartmut; Vollebregt, Madelon A.; Strehl, Ute; K. Loo, Sandra (European Child & Adolescent Psychiatry, 2018)
Neurofeedback (NF) has gained increasing interest in the treatment of attention-deficit/hyperactivity disorder (ADHD). Given learning principles underlie NF, lasting clinical treatment effects may be expected. This systematic review and meta-analysis addresses the sustainability of neurofeedback and control treatment effects by considering randomized controlled studies that conducted follow-up (FU; 2-12 months) assessments among children with ADHD. PubMed and Scopus databases were searched through November 2017. Within-group and between-group standardized mean differences (SMD) of parent behavior ratings were calculated and analyzed. Ten studies met inclusion criteria (NF: ten studies, N = 256; control: nine studies, N = 250). Within-group NF effects on inattention were of medium effect size (ES) (SMD = 0.64) at post-treatment and increased to a large ES (SMD = 0.80) at FU. Regarding hyperactivity/impulsivity, NF ES were medium at post-treatment (SMD = 0.50) and FU (SMD = 0.61). Non-active control conditions yielded a small significant ES on inattention at post-treatment (SMD = 0.28) but no significant ES at FU. Active treatments (mainly methylphenidate), had large ES for inattention (post: SMD = 1.08; FU: SMD = 1.06) and medium ES for hyperactivity/impulsivity (post: SMD = 0.74; FU: SMD = 0.67). Between-group analyses also revealed an advantage of NF over non-active controls [inattention (post: SMD = 0.38; FU: SMD = 0.57); hyperactivity-impulsivity (post: SMD = 0.25; FU: SMD = 0.39)], and favored active controls for inattention only at pre-post (SMD = - 0.44). Compared to non-active control treatments, NF appears to have more durable treatment effects, for at least 6 months following treatment. More studies are needed for a properly powered comparison of follow-up effects between NF and active treatments and to further control for non-specific effects.
EVALuna2:36374

Swiprosin-1/ EFhd2: from Immune Regulator to Personality and Brain Disorders - Kogias, Georgios; Kornhuber, Johannes; Reimer, Dorothea; Mielenz, Dirk; Müller, Christian P. (Neurosignals, 2019)
BACKGROUND/AIMS: Swiprosin-1/ EF-hand domain 2 (EFhd2) is a Ca2+ sensor protein that plays an important role in the immune system. Its abundant expression in the brain, however, suggested also a role in neuronal circuits and behavior. METHODS: Here we review recent discoveries on the structure and molecular function, its role in immunity and its function in the brain regarding behavioral control and pathologies. RESULTS: While EFhd2 did not emerge as a vital protein for brain development, changes in its expression may nevertheless shape the adult behavioral repertoire significantly and contribute to adult personality traits. A defective function of EFhd2 may also render individuals more prone to the development of psychiatric disorders. Most prominently, EFhd2 proved to be a resilience factor protecting from fast establishment of drug addiction. Moreover, EFhd2 is critical for adult neurogenesis and as a modulator of monoaminergic systems. CONCLUSION: Dysregulated activity of EFhd2 is increasingly considered as a contributing factor for the development of numerous neurodegenerative disorders. Whether EFhd2 can be used as biomarker or in therapeutic approaches has to be addressed in future research.
CRIS-Team Scopus Importer:2019-11-26
Keywords: Swiprosin-1; EFhd2; Immunity; Personality; Neurogenesis; Dopamine; Addiction; Neurodegenerative disorders

Swiprosin1/EFhd2 is involved in the monoaminergic and locomotor responses of psychostimulant drugs - Kogias, Georgios; Zheng, Fang; Kalinichenko, Liubov; Kornhuber, Johannes; Alzheimer, Christian; Mielenz, Dirk; Müller, Christian P. (Journal of Neurochemistry, 2020)
Psychostimulants are widely abused drugs that may cause addiction in vulnerable individuals. While the reward circuitry of the brain is involved in addiction establishment, various pathways in the brain may provide protection at the molecular level that limits the acute and chronic effects of drugs. These targets may be used for strategies designed to prevent and treat addiction. Swiprosin-1/EF hand domain 2 (EFhd2) is a Ca2+-binding cytoskeletal adaptor protein involved in sensation-seeking behaviour, anxiety and alcohol addiction. Here, we tested how EFhd2 contributes to the physiological and behavioural effects of the psychostimulant drugs methamphetamine (METH) and cocaine. An in vivo microdialysis study in EFhd2 knockout mice revealed that EFhd2 controls METH- and cocaine-induced changes in extracellular dopamine, serotonin and noradrenaline levels through different mechanisms in the nucleus accumbens and prefrontal cortex. Electrophysiological recordings in a slice preparation showed that a lack of EFhd2 increases dopaminergic neuronal activity in the ventral tegmental area and increases the sensitivity of neurons to stimulation. We report a role of EFhd2 in METH-induced locomotor activation and in the conditioned locomotor effects. No role, however, was observed in the establishment of METH- or cocaine-induced conditioned place preference. These findings may suggest that EFhd2 modulates the activity of the dopaminergic system and the neurochemical effects of METH and cocaine, which translate into a modulation of the behavioural effects of these drugs at the level of the acute and conditioned locomotor activity. (Figure presented.).
CRIS-Team Scopus Importer:2020-02-14
Keywords: cocaine; dopamine; EFhd2; methamphetamine; noradrenaline; serotonin; Swiprosin-1

Symptombelastung, Inanspruchnahme des Gesundheitssystems und Todesumstände von Menschen mit Demenz in der letzten Lebensphase: der Bayerische Demenz Survey (BayDem) - Kratzer, André; Karrer, Linda; Dietzel, Nikolas; Wolff, Franziska; Hess, Manuela; Kolominsky-Rabas, Peter; Grässel, Elmar (Gesundheitswesen, 2020)
Background Dementia is usually a life-limiting disease. However, evidence-based guidelines for palliative care for people with dementia (PwD) are currently lacking. One reason for this is the dearth of reliable empirical data on PwD at the end of life. The aim of this study is to describe the symptom burden, causes of death, places of death and the use of various health services for PwD at the end of life. Methods The Bavarian Dementia Survey (BayDem) was a multi-center, longitudinal study at 3 different sites in Bavaria, Germany (Dachau, Kronach, Erlangen). Participants were PwD defined by ICD-10 and their informal caregivers. Data were collected in standardized face-to-face interviews in cooperation with local actors. In order to obtain comparable groups, deceased and non-deceased PwD were matched using 1:1 propensity score matching. For the statistical analyses, McNemar tests as well as paired t-tests were used. Results In this analysis, 58 deceased and 58 non-deceased PwD were studied (n=116). In most cases, PwD died at home (36.2%), in hospital (25.9%) or in a nursing home (19.0%), but no one in palliative care. The most common causes of death were respiratory (13.8%) and cardiovascular complications (12.1%) as well as stroke (12.1%). PwD at the end of life showed more pronounced physical comorbidities than the other PwD (Charlson-Index: M=2.75 vs. M=1.80; p=0.030, Cohen's d=0.425) and were therefore admitted to hospital (46.6 vs. 12.1%, p<0.001, OR=6.250) or emergency departments (22.4 vs. 3.4%, p=0.007, OR=6.500) more frequently. Behavioral and psychological symptoms were very pronounced (NPI Score: M=31.67 vs. M=24.77, p=0.118, Cohen's d=0.303). Nevertheless, the utilization of outpatient health services was low. Conclusion The results underline the need to develop evidence-based guidelines to provide palliative care specifically adapted to the needs of PwD at the end of life. In this context, the high incidence of behavioral and psychological symptoms should be taken into account, as should the high incidence of physical comorbidities. Considering the frequent hospital admissions, special attention should also be paid to the development of recommendations for the inpatient sector (acute hospital and palliative care unit).
CRIS-Team Scopus Importer:2020-02-04
Keywords: Death; Dementia; End of life; Palliative care; Symtom burden; Utilization

Synaptic Vesicle Pool Monitoring with Synapto-pHluorin - Dahlmanns, Marc; Dahlmanns, Jana (Synaptic Vesicles, 2022)
Synaptic vesicle exocytosis can be monitored with genetically encoded pH sensors in an in vitro fluorescence microscopy setup. Here, we describe a workflow starting with preparation of a primary cell culture to eventually estimate synaptic vesicle pool sizes based on electrical current-evoked vesicle release, which is reported by the synaptobrevin 2-EGFP fusion protein synapto-pHluorin (spH) that is expressed inside the synaptic vesicle membrane. The readily releasable pool and the recycling pool of synaptic vesicles are released separately in response to electrical stimulation. As vesicle reacidification is blocked in this experimental design, every released vesicle is counted only once. This spH-based approach offers different information than styryl-dye (FM dyes)-based approaches because the total synaptic pool size is measured by an alkalinization step. This provides a normalization constant for quantifying and comparing the synaptic vesicle pool sizes. In addition to investigation of basic research questions, spH-reported vesicle release is valuable to determine presynaptic effects of, e.g., pharmacological drug treatments.
CRIS-Team Scopus Importer:2022-02-11
Keywords: Live-cell fluorescence imaging; Readily releasable pool; Recycling pool; Synaptic vesicle pools; Synapto-pHluorin

Synthesis and characterization of a new two photon excitable acid sphingomyelinase FRET probe - Mohamed, Zain H.; Rhein, Cosima; Schmid, Benjamin; Tripal, Philipp; Kornhuber, Johannes; Arenz, Christoph (Bioorganic & medicinal chemistry, 2021)
Recently, FRET probes for acid sphingomyelinase (ASM) have enabled the observation of enzyme activity in intact cells for the first time. Here we present an ASM FRET probe specifically optimized for 2-photon excitation. To facilitate probe characterization and comparison to the previous probe, we mixed the two intact probes with defined amounts of the probes' ceramide cleavage products and mounted them on lipid beads. Directly excited NBD FRET acceptor fluorescene proved to be a useful means of reference and showed that the new probe is brighter, albeit only moderately, than the previous one. The new probe was then used to detect inhibition by various ASM inhibitors microscopically for the first time. Also in cells, directly excited acceptor fluorescence proved to be a useful parameter in addition to FRET to visualize inhibition of ASM.
CRIS-Team Scopus Importer:2021-07-30
Keywords: Antidepressants; Enzyme inhibitors; FRET probes; Förster resonance energy transfer (FRET); Sphingolipids; Two-photon microscopy

Tagespflege: Wer nutzt sie und wer möchte sie nutzen? Multivariable Analyse der aktuellen und zukünftigen Inanspruchnahme der Tagespflege bei der häuslichen Pflege - Bösl, Sophia; Diehl, Kristina; Pendergrass, Anna; Grässel, Elmar (Gesundheitswesen, Supplement, 2024)
Background Adult day care serves to ease the burden on informal caregivers and to provide adequate care and support for care recipients. Across Bavaria and Germany, adult day care is attended by 4 % of all care recipients. The aim of the secondary analysis was to identify variables linked to the current or desired future use of adult day care services. Methodology For the cross-sectional study Benefits of Being a Caregiver (“Zugewinne durch die Pflege”), informal caregivers of geriatric care receiver were surveyed in Bavaria from October 2019 to March 2020 (age > 65; n = 958). Data regarding caregiving situation, characteristics of informal caregivers and care recipients, and sociodemographic information were collected. Two binary logistic regression analyses were conducted to identify predictors of current or desired adult day care service use. Results Adult day care was used by 7.3 % (n = 70) of informal caregivers. Utilization was associated with dementia and high care degree requirements of the care recipient(Nagelkerke's R2 = 0.200). Of the 888 informal caregivers not using adult day care services, 223 (25.1 %) expressed a desire to use them. This was associated with care recipients suffering from dementia, a poor previous relationship, and a high subjective burden on the informal caregiver (Nagelkerke’s R2 = 0.083). Conclusion The utilization rate of adult day care was found to be higher than reported in Bavarian or German care statistics. Dementia and an increased need for care of the care recipient were associated with utilization, but contrary to reports in literature, no association with everyday limitations, sex, education, or duration of care was found. More than two-thirds of Bavarian informal caregivers do not want to use adult day care services either now or in the future.
CRIS-Team Scopus Importer:2024-03-08
Keywords: adult day care centers; care recipient; informal caregivers; long-term care

Targeted mass spectrometry of ketamine and its metabolites cis-6-hydroxynorketamine and norketamine in human blood serum - Kurzweil, Lisa; Danyeli, Lena; Şen, Zümrüt Duygu; Fejtová, Anna; Walter, Martin; Gensberger-Reigl, Sabrina (Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2020)
Ketamine (KET) was originally developed as an anesthetic agent but has also attracted attention for further clinical applications such as medical treatment of depression or pain. The use of KET induces dissociation and emergence delirium. Due to these effects, KET has a high potential for abuse. In order to investigate metabolization of KET or to confirm misuse of KET, highly sensitive analytical methods that cover KET and its metabolites are necessary. A new analytical approach for simultaneous analysis of KET and its metabolites cis-6-hydroxynorketamine (HNK) and norketamine (NK) was established. The compounds were extracted from human blood serum by ultrafiltration and solid phase extraction with subsequent vacuum evaporation. The compounds were analyzed by non-enantioselective ultra-high performance micro-flow liquid chromatography (Waters ACQUITY UPLC® M-Class HSS T3 column, 0.1% formic acid and acetonitrile with 0.1% formic acid, 14 µL/min flow rate) coupled with tandem mass spectrometry in positive scheduled multiple reaction monitoring mode. Validation parameters such as linearity, precision, recovery, accuracy, stability, limit of detection (LOD), and limit of quantification (LOQ) were proven. LOD for KET and NK was 0.08 ng/mL and LOQ were 0.5 ng/mL and 0.6 ng/mL, respectively. For HNK, LOD was 0.1 ng/mL and LOQ 0.8 ng/mL. The method was then successfully applied to quantify KET, HNK, and NK in blood serum samples from subjects who received KET intravenously. A novel method for the simultaneous analysis of KET, NK, and HNK was established. This new method could now be used for clinical trials investigating KET and its metabolites HNK and NK or for forensic analysis in order to confirm KET abuse.
CRIS-Team Scopus Importer:2020-06-16
Keywords: cis-6-Hydroxynorketamine; Human blood serum; Ketamine; MicroLC–ESI–sMRM; Norketamine; Targeted mass spectrometry

Teaching NeuroImages: Stroke and bilateral visual loss in a young adult: More than coincidence - Volbers, Bastian; Kaldefoss, K.; Bergua, A.; Kloska, Stephan; Schwab, Sibylle; Köhrmann, Martin (Neurology, 2012)
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Technology Integration in the Daily Activities of the Elderly - Soutschek, Stefan; Spiegl, Werner; Steidl, Stefan; Hornegger, Joachim; Erzigkeit, Hellmut; Kornhuber, Johannes (Künstliche Intelligenz, 2008)
A continuous increase of the anticipated average life is expected in the near future. We have to deal with the consequences of aging, such as loneliness in an environment characterized by technology or the need to help elderly people. Technical solutions are required that solve the occurring problems associated with aging and are accepted and used. This work faces the challenge of improving the early detection of diseases like dementia, using an intelligent dialogue system that improves the chance for integrating applications of telemedicine in an intelligent home environment.

Telemedicine: Comprehensive coverage and quality - Not a contradiction : Practical experience from the stroke network with telemedicine in northern Bavaria (STENO) - Breuer, Lorenz; Erbguth, F.; Oschmann, P.; Schwab, Sibylle (Der Nervenarzt, 2017)
Telemedicine is widely used in the field of stroke treatment. Following the pioneering and implementation phase, the quality of the whole stroke treatment process needs to be ensured in telemedically connected hospitals. This is particular important for telestroke hospitals without neurological expertise and can be achieved by integrating telemedicine into the stroke unit concept and stroke networks. The Stroke Network with Telemedicine in Northern Bavaria (STENO) provides an example of how quality management can be practically implemented. The implementation of STENO has established a network-wide quality management system which has been certified according to DIN EN ISO 9001:2008 since 2011.
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Telemedicine in stroke care - Breuer, Lorenz; Schwab, Sibylle (Medizinische Klinik - Intensivmedizin und Notfallmedizin, 2017)
Telemedicine is already widely used in many telestroke networks and ensures stroke treatment close to the patient's home in rural and medically underserved areas. This is particularly effective when telemedicine is integrated into a stroke unit concept. While telemedically based thrombolysis therapy has become routine practice for many years, practical implementation of comprehensive mechanical thrombectomy and the related processes remains challenging. The main tasks for the future further include development of a structured stroke aftercare system in neurologically underserved areas and permanent assurance of high-quality stroke care in telemedically connected sites.
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