Mediating Role of the Reward Network in the Relationship between the Dopamine Multilocus Genetic Profile and Depression
Multiple genetic loci in the dopamine (DA) pathway have been associated with depression symptoms in patients with major depressive disorder (MDD). However, the neural mechanisms underlying the polygenic effects of the DA pathway on depression remain unclear. We used an imaging genetic approach to in...
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Published in | Frontiers in molecular neuroscience Vol. 10; p. 292 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Research Foundation
14.09.2017
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | Multiple genetic loci in the dopamine (DA) pathway have been associated with depression symptoms in patients with major depressive disorder (MDD). However, the neural mechanisms underlying the polygenic effects of the DA pathway on depression remain unclear. We used an imaging genetic approach to investigate the polygenic effects of the DA pathway on the reward network in MDD. Fifty-three patients and 37 cognitively normal (CN) subjects were recruited and underwent resting-state functional magnetic resonance imaging (R-fMRI) scans. Multivariate linear regression analysis was employed to measure the effects of disease and multilocus genetic profile scores (MGPS) on the reward network, which was constructed using the nucleus accumbens (NAc) functional connectivity (NAFC) network. DA-MGPS was widely associated within the NAFC network, mainly in the inferior frontal cortex, insula, hypothalamus, superior temporal gyrus, and occipital cortex. The pattern of DA-MGPS effects on the fronto-striatal pathway differed in MDD patients compared with CN subjects. More importantly, NAc-putamen connectivity mediates the association between DA MGPS and anxious depression traits in MDD patients. Our findings suggest that the DA multilocus genetic profile makes a considerable contribution to the reward network and anxious depression in MDD patients. These results expand our understanding of the pathophysiology of polygenic effects underlying brain network abnormalities in MDD. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Jean-Marc Taymans, Institut National de la Santé et de la Recherche Médicale, France Reviewed by: Gianluca Serafini, University of Genoa, Italy; Yan-Xue Xue, Peking University, China |
ISSN: | 1662-5099 1662-5099 |
DOI: | 10.3389/fnmol.2017.00292 |