Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users

Havranek MM, Vonmoos M, Müller C, Buetiger JR, Tasiudi E, Hulka LM, Preller KH, Moessner R, Gruenblatt E, Seifritz E, Quednow BB (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Neuropsychopharmacology Nature Publishing Group: Open Access Hybrid Model Option A

Book Volume: 40

Pages Range: 2929-37

Journal Issue: 13

DOI: 10.1038/npp.2015.146

Abstract

Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence.

Authors with CRIS profile

Christiane Müller Medizinische Fakultät

Additional Organisation(s)

Department of Psychiatry and Psychotherapy

Involved external institutions

University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Havranek, M.M., Vonmoos, M., Müller, C., Buetiger, J.R., Tasiudi, E., Hulka, L.M.,... Quednow, B.B. (2015). Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users. Neuropsychopharmacology, 40(13), 2929-37. https://dx.doi.org/10.1038/npp.2015.146

MLA:

Havranek, Michael M., et al. "Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users." Neuropsychopharmacology 40.13 (2015): 2929-37.

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