Serotonergic modulation in executive functioning: Linking genetic variations to working memory performance

• Published in: Neuropsychologia 2011-11, Vol.49 (13), p.3776-3785
• Main Authors: Enge, Sören, Fleischhauer, Monika, Lesch, Klaus-Peter, Reif, Andreas, Strobel, Alexander
• Format: Article
• Language: English
• Subjects: 5-HTTLPR; Adolescent; Adult; Behavioral psychophysiology; Biological and medical sciences; Electroencephalography; Evoked Potentials - genetics; Executive Function - physiology; Executive functioning; Female; Fundamental and applied biological sciences. Psychology; Genetic Linkage; Genetic Variation - genetics; Genotype; Humans; Inhibitory control; Male; MAOA-uVNTR; Memory, Short-Term - physiology; Minisatellite Repeats - genetics; Monoamine Oxidase - genetics; NET −3081; Neuropsychological Tests; Neurotransmission and behavior; Norepinephrine; P3b; Polymorphism, Genetic - genetics; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Serotonin; Serotonin Plasma Membrane Transport Proteins - genetics; Working memory; Young Adult
• ISSN: 0028-3932; 1873-3514
• DOI: 10.1016/j.neuropsychologia.2011.09.038

► Genetic variations of the 5-HT pathway (5-HTTLPR, MAOA) impact on working memory. ► 5-HT modulation is evidenced by RT, error rate and ERP associations (via n-back). ► Epistatic effects of 5-HT polymorphisms with NE gene variation (NET −3081) emerged. ► 5-HT genes may impact on inhibitory control as implicated in working memory. ► Results suggest a crucial role of 5-HT neuromodulation in executive functioning. Emerging evidence from studies using, for example, acute tryptophan depletion or investigating genetic variation of genes related to the serotonin signaling pathway suggest a role of serotonin in executive functions such as top-down attention, working memory and inhibitory control. In the current study, we aimed at extending this evidence by using the n-back task to examine working memory performance of 130 participants via behavioral and neurophysiological indices and by focusing on variations within genes encoding key regulators of the serotonergic system: the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and a repeat polymorphism in the transcriptional control region of the monoamine-oxidase gene (MAOA-uVNTR). Because serotonin and norepinephrine systems have been shown to be structurally and functionally highly interrelated, we also examined a novel polymorphism in the promoter region of the norepinephrine transporter gene (NET −3081) in anticipation of epistatic effects. We found that carriers of 5-HTTLPR and MAOA-uVNTR alleles recently implicated in executive processing showed a more efficient executive control of working memory-related performance as evidenced by reaction time, error rate as well as N2 and P3b event-related potential measures. This impact was further supported by interactions with the NET polymorphism. Linking serotonergic influence to mechanisms of inhibitory response control implicated in working memory, our results provide further support for and add new evidence concerning the importance of serotonergic neuromodulation in executive functioning.