TY - JOUR
T1 - Dopamine multilocus genetic profiles predict sex differences in reactivity of the human reward system
AU - Diekhof, Esther K.
AU - Richter, Anja
AU - Brodmann, Katja
AU - Gruber, Oliver
N1 - Funding Information:
We are grateful to Maria Keil, Peter Dechent, Ilona Pfahlert, Britta Perl and the staff of the unit ?MR-Research in Neurology and Psychiatry? at the University Medical Center G?ttingen (Germany) for their valuable work with MRI data acquisition. We thank all participants in this study.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Sex differences in the neural processing of decision-making are of high interest as they may have pronounced effects on reward- and addiction-related processes. In these, the neurotransmitter dopamine plays a central role by modulating the responsiveness of the reward circuitry. The present functional magnetic resonance imaging study aimed to explore sex and dopamine transmission interactions in decision-making. 172 subjects (111 women) performed a behavioral self-control task assessing reward-related activation during acceptance and rejection of conditioned rewards. Participants were genotyped for six key genetic polymorphisms in the dopamine system that have previously been associated with individual differences in reward sensitivity or dopaminergic transmission in the human striatum, such as rs7118900 (dopamine receptor D2 (DRD2) Taq1A), rs1554929 (DRD2 C957T), rs907094 (DARPP-32), rs12364283 (DRD2), rs6278 (DRD2), and rs107656 (DRD2). The selected polymorphisms were combined in a so-called multilocus genetic composite (MGC) score reflecting the additive effect of different alleles conferring relative increased dopamine transmission in every individual. We successfully demonstrated that reward-related activation in the ventral striatum and ventral tegmental area (VTA) was significantly modulated by biologically informed MGC profiles and sex. When comparing men and women with low MGC profiles that may indicate lower dopamine transmission, only women displayed a reduced down-regulation of activation in the mesolimbic system during reward rejection and additionally, a significant non-linear u-shape relationship between MGC score and VTA activation. Taken together, by integrating neuroimaging and genetics, the present findings contribute to a better understanding of the effects of sex differences on the human brain.
AB - Sex differences in the neural processing of decision-making are of high interest as they may have pronounced effects on reward- and addiction-related processes. In these, the neurotransmitter dopamine plays a central role by modulating the responsiveness of the reward circuitry. The present functional magnetic resonance imaging study aimed to explore sex and dopamine transmission interactions in decision-making. 172 subjects (111 women) performed a behavioral self-control task assessing reward-related activation during acceptance and rejection of conditioned rewards. Participants were genotyped for six key genetic polymorphisms in the dopamine system that have previously been associated with individual differences in reward sensitivity or dopaminergic transmission in the human striatum, such as rs7118900 (dopamine receptor D2 (DRD2) Taq1A), rs1554929 (DRD2 C957T), rs907094 (DARPP-32), rs12364283 (DRD2), rs6278 (DRD2), and rs107656 (DRD2). The selected polymorphisms were combined in a so-called multilocus genetic composite (MGC) score reflecting the additive effect of different alleles conferring relative increased dopamine transmission in every individual. We successfully demonstrated that reward-related activation in the ventral striatum and ventral tegmental area (VTA) was significantly modulated by biologically informed MGC profiles and sex. When comparing men and women with low MGC profiles that may indicate lower dopamine transmission, only women displayed a reduced down-regulation of activation in the mesolimbic system during reward rejection and additionally, a significant non-linear u-shape relationship between MGC score and VTA activation. Taken together, by integrating neuroimaging and genetics, the present findings contribute to a better understanding of the effects of sex differences on the human brain.
KW - Functional connectivity
KW - Genotype
KW - Mesolimbic system
KW - Sex
KW - Single-nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85101456429&partnerID=8YFLogxK
U2 - 10.1007/s00429-021-02227-6
DO - 10.1007/s00429-021-02227-6
M3 - Article
AN - SCOPUS:85101456429
SN - 1863-2653
VL - 226
SP - 1099
EP - 1114
JO - Brain Structure and Function
JF - Brain Structure and Function
IS - 4
ER -