Nonlinear modulation of interacting between <i>COMT</i> and depression on brain function

Gong, Liang; He, Cancan; Yin, Yi; Ye, Q.; Bai, Feng; Yuan, Yonggui; Zhang, H.; Lv, Luxian; Zhang, Z.; Xie, Chunming

doi:10.1016/j.eurpsy.2017.05.024

Cited by 20 publications

(13 citation statements)

References 47 publications

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“…Five of the included studies also investigated patient groups, four of which reported results independently for healthy participants. The remaining study by Gong et al (2017) reported no significant main effect of COMT rs4680 across a group including healthy participants and those with a diagnosis of major depressive disorder which is noted where applicable.…”

Section: Resultsmentioning

confidence: 87%

“…One interpretation of the current findings is that the effect of COMT rs4680 on functional connectivity is nuanced, dynamic and specific to inter‐regional circuits. Indeed, global functional connectivity density results of three studies have shown no difference with COMT rs4680 during resting‐state (Gong et al., 2017; Li et al., 2016; Tian et al., 2013), suggesting a global measure is insufficient. The trend towards greater resting‐state functional connectivity with the Val allele, and greater task‐based connectivity with the Met allele could support a role for COMT rs4680 in cognitive flexibility, with the Met allele being advantageous for targeted and sustained signalling, improving task performance.…”

Section: Discussionmentioning

confidence: 99%

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The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review

Morris

Grace

Woods

et al. 2020

Eur J of Neuroscience

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Catechol-O-methyltransferase (COMT) is an enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to any catechol-containing molecule, this is an important step in the degradation of families of molecules such as the catecholamines (dopamine, epinephrine and norepinephrine Guldberg & Marsden, 1975; Weinshilboum, Otterness, & Szumlanski, 1999) and the catecholoestrogens (Ball, Knuppen, Haupt, & Breuer, 1972). The COMT gene includes a number of single nucleotide polymorphisms (SNPs), the most commonly studied being

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Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review

Morris

Grace

Woods

et al. 2020

Eur J of Neuroscience

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“…Several studies reported an inverted U-shaped relationship between DA signaling and fronto-striatal brain activity and cognitive performance in healthy participants and subjects with Parkinson's disease (Bertolino et al, 2009 ; Cools and D'Esposito, 2011 ; Fallon et al, 2013 ). Our recent published work also revealed a non-linear modulation of the interaction between the COMT gene and depression on brain function (Gong et al, 2017a ). Interestingly, the interaction regions identified in the present study included the mOFC, rACC, and putamen, which functionally encompass the fronto-striatal pathway, and these are implicated in reward anticipation, valuation, motivation, and attainment (Dillon et al, 2014 ).…”

Section: Discussionmentioning

confidence: 75%

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

Gong¹,

He²,

Yin³

et al. 2017

Front. Mol. Neurosci.

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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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“…A similar U-shaped genetic effect is observed in the COMT gene in Parkinson’s disease ( Fallon et al, 2013 ), during attentional formation processing, Val homozygotes showed higher dorsolateral prefrontal cortex activity than Met carriers, while an opposite pattern was observed in healthy older individuals. Another study on MDD found a nonlinear modulation effect of COMT on global functional connectivity density ( Gong et al, 2017 ). In the control system, the prefrontal cortex showed inverted U-shaped modulation, but in the processing system, the hippocampus and occipital cortex showed U-shaped modulation.…”

Section: Discussionmentioning

confidence: 99%

Age-related atrophy of cortical thickness and genetic effect of ANK3 gene in first episode MDD patients

Cheng

Dong

et al. 2020

NeuroImage: Clinical

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Brain ageing is thought to be related to geriatric depression, but the relationship between ageing and depression among middle aged individuals is unknown. The present study aimed to evaluate whether the age-related reduction of brain cortical thickness (CT) can be found in adult first-episode MDD patients, as well as to identify the possible genetic effect of the ANK3 gene polymorphism age-relates CT reduction. This study recruited 153 first-episode MDD patients with a disease duration < 2 years and 276 healthy controls (HC), and the CT of 68 whole brain regions and two ANK3 SNPs (rs1994336 and rs10994359) were analyzed. The results showed that although the CT of both groups was negative correlated with age, the MDD group had significant greater age-related decrease in CT than the HC group (–9.35 × 10 −3 mm/year for MDD vs. –1.23 × 10 −3 mm/year for HC in the left lateral orbitofrontal lobe). The multivariate analysis of covariance (MANCOVA) results yielded significant interactions of diagnosis × age, genotype × age and diagnosis × genotype interaction for rs10994359. In HC, the C allele showed a protective effect on age-related CT reduction. The reduction in CT with age was several times as greater in non-C carriers as in C carriers (–3.54 × 10 −3 vs.–0.15 × 10 −3 mm/year in left supramarginal gyrus) for HC. However, this protective effect disappeared in patients with MDD. We did not find a clear effect of rs1994336 on the age-related CT reduction. The findings indicate that the widespread accelerated brain ageing occurs early in adult-onset depression and this ageing may be a pathological mechanisms of depression rather than an outcome of the disease. The ANK3 rs10994359 polymorphism may partially affect regional cortical ageing in MDD.

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Nonlinear modulation of interacting between COMT and depression on brain function

Abstract: Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.

Cited by 20 publications

References 47 publications

The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review

The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review

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

Age-related atrophy of cortical thickness and genetic effect of ANK3 gene in first episode MDD patients

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