Year : 2012 Dopamine inactivation efficacy related to functional DAT 1 and COMT variants influences motor response evaluation

BACKGROUND: Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task. METHODS: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val(158)Met and two DAT1 polymorphisms (variable number tandem repeats in the 3’-untranslated region and in intron 8). RESULTS: The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500-1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered. CONCLUSIONS: Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming. DOI: https://doi.org/10.1371/journal.pone. 0037814 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-74392 Published Version Originally published at: Bender, Stephan; Rellum, Thomas; Freitag, Christine; Resch, Franz; Rietschel, Marcella; Treutlein, Jens; Jennen-Steinmetz, Christine; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred (2012). Dopamine inactivation efficacy related to functional DAT1 and COMT variants influences motor response evaluation. PLoS ONE, 7(5):e37814. DOI: https://doi.org/10.1371/journal.pone. 0037814 Dopamine Inactivation Efficacy Related to Functional DAT1 and COMT Variants Influences Motor Response Evaluation Stephan Bender*, Thomas Rellum, Christine Freitag, Franz Resch, Marcella Rietschel, Jens Treutlein, Christine Jennen-Steinmetz, Daniel Brandeis, Tobias Banaschewski, Manfred Laucht 1 Section for Clinical Neurophysiology and Multimodal Neuroimaging, Child and Adolescent Psychiatric Department, Technical University Dresden, Dresden, Germany, 2 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Johann-Wolfgang-Goethe University, Frankfurt am Main, Germany, 3 Department of Child and Adolescent Psychiatry and Psychotherapy, Heidelberg University Hospital, Heidelberg, Germany, 4 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany, 5 Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany, 6 Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany, 7 Department of Child and Adolescent Psychiatry, University of Zürich, Zürich, Switzerland, 8 Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland, 9 Department of Psychology, University of Potsdam, Potsdam, Germany