Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Gong L

PROVIDER: S-EPMC5603675 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Gong Liang L He Cancan C Yin Yingying Y Wang Hui H Ye Qing Q Bai Feng F Yuan Yonggui Y Zhang Haisan H Lv Luxian L Zhang Hongxing H Zhang Zhijun Z Xie Chunming C

Frontiers in molecular neuroscience 20170914

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 magne ...[more]

PMID: 28959185

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Project description:The efficacy of dopamine agonists in treating major depressive disorder has been hypothesized to stem from effects on ventrostriatal dopamine and reward function. However, an important question is whether dopamine agonists are most beneficial for patients with reward-based deficits. This study evaluated whether measures of reward processing and ventrostriatal dopamine function predicted response to the dopamine agonist, pramipexole (ClinicalTrials.gov Identifier: NCT02033369). Individuals with major depressive disorder (n = 26) and healthy controls (n = 26) (mean ± SD age = 26.5 ± 5.9; 50% female) first underwent assessments of reward learning behaviour and ventrostriatal prediction error signalling (measured using functional MRI). 11C-(+)-PHNO PET before and after oral amphetamine was used to assess ventrostriatal dopamine release. The depressed group then received open-label pramipexole treatment for 6 weeks (0.5 mg/day titrated to a maximum daily dose of 2.5 mg). Symptoms were assessed weekly, and reward learning was reassessed post-treatment. At baseline, relative to controls, the depressed group showed lower reward learning (P = 0.02), a trend towards blunted reward-related prediction error signals (P = 0.07), and a trend towards increased amphetamine-induced dopamine release (P = 0.07). Despite symptom improvements following pramipexole (Cohen's d ranging from 0.51 to 2.16 across symptom subscales), reward learning did not change after treatment. At a group level, baseline reward learning (P = 0.001) and prediction error signalling (P = 0.004) were both associated with symptom improvement, albeit in a direction opposite to initial predictions: patients with stronger pretreatment reward learning and reward-related prediction error signalling improved most. Baseline D2/3 receptor availability (P = 0.02) and dopamine release (P = 0.05) also predicted improvements in clinical functioning, with lower D2/3 receptor availability and lower dopamine release predicting greater improvements. Although these findings await replication, they suggest that measures of reward-related mesolimbic dopamine function may hold promise for identifying depressed individuals likely to respond favourably to dopaminergic pharmacotherapy.

Dataset Information

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

Publications

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

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