Regina Boecker-Schlier1, Nathalie E Holz1, Arlette F Buchmann1, Dorothea Blomeyer1, Michael M Plichta1, Christine Jennen-Steinmetz2, Isabella Wolf3, Sarah Baumeister1, Jens Treutlein4, Marcella Rietschel4, Andreas Meyer-Lindenberg5, Tobias Banaschewski1, Daniel Brandeis6, Manfred Laucht7. 1. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 2. Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 3. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; Department Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 4. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 5. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 6. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, ETH Zurich, Zurich, Switzerland. 7. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; Department of Psychology, University of Potsdam, Potsdam, Germany. Electronic address: manfred.laucht@zi-mannheim.de.
Abstract
BACKGROUND: Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing. METHODS: 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. RESULTS: At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. CONCLUSIONS: These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention.
BACKGROUND: Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMTVal(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing. METHODS: 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. RESULTS: At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. CONCLUSIONS: These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention.
Authors: Andrew M Novick; Mateus L Levandowski; Laura E Laumann; Noah S Philip; Lawrence H Price; Audrey R Tyrka Journal: J Psychiatr Res Date: 2018-02-13 Impact factor: 4.791
Authors: Shannon D Donofry; Chelsea M Stillman; Jamie L Hanson; Margaret Sheridan; Shufang Sun; Eric B Loucks; Kirk I Erickson Journal: Neurosci Biobehav Rev Date: 2021-10-05 Impact factor: 8.989
Authors: Katherine S Young; Camilla Ward; Meghan Vinograd; Kelly Chen; Susan Y Bookheimer; Robin Nusslock; Richard E Zinbarg; Michelle G Craske Journal: Eur J Neurosci Date: 2022-01-19 Impact factor: 3.698