Mediating Role of the Reward Network in the Relationship between the Dopamine Multilocus Genetic Profile and Depression

• Published in: Frontiers in molecular neuroscience Vol. 10; p. 292
• Main Authors: Gong, Liang, He, Cancan, Yin, Yingying, Wang, Hui, Ye, Qing, Bai, Feng, Yuan, Yonggui, Zhang, Haisan, Lv, Luxian, Zhang, Hongxing, Zhang, Zhijun, Xie, Chunming
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 14.09.2017; Frontiers Media S.A
• Subjects: Alcohol; Brain research; Cortex (frontal); Cortex (insular); depression; Dopamine; Functional magnetic resonance imaging; Genes; Hospitals; Hypothalamus; imaging genetics; Medical screening; Mental depression; Mental disorders; Metabolism; multilocus genetic profile; Neostriatum; Neural networks; Neuroimaging; Neuroscience; Nucleus accumbens; Occipital lobe; Polygenic inheritance; Polymorphism; Psychiatry; Putamen; Reinforcement; reward network; Studies; Superior temporal gyrus; Temporal cortex; Temporal gyrus; China; reward network; depression; imaging genetics; multilocus genetic profile; dopamine
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2017.00292

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.