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Nonlinear modulation of interacting between COMT and depression on brain function

Published online by Cambridge University Press:  23 March 2020

L. Gong ,
C. He ,
Y. Yin ,
Q. Ye ,
F. Bai ,
Y. Yuan ,
H. Zhang ,
L. Lv ,
H. Zhang  and
Z. Zhang
...Show all authors
L. Gong
Affiliation:
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, No. 87, DingJiaQiao Road, Nanjing, 210009Jiangsu, PR China
C. He
Affiliation:
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, No. 87, DingJiaQiao Road, Nanjing, 210009Jiangsu, PR China
Y. Yin
Affiliation:
Department of Psychology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009Jiangsu, China
Q. Ye
Affiliation:
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, No. 87, DingJiaQiao Road, Nanjing, 210009Jiangsu, PR China
F. Bai
Affiliation:
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, No. 87, DingJiaQiao Road, Nanjing, 210009Jiangsu, PR China Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, 210009Jiangsu, China
Y. Yuan
Affiliation:
Department of Psychology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009Jiangsu, China Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, 210009Jiangsu, China
H. Zhang
Affiliation:
Department of Psychiatry, Henan Mental Hospital, the Second Hospital of Xinxiang Medical University, Xinxiang, 453002Henan, China
L. Lv
Affiliation:
Department of Psychiatry, Henan Mental Hospital, the Second Hospital of Xinxiang Medical University, Xinxiang, 453002Henan, China
H. Zhang
Affiliation:
Department of Psychiatry, Henan Mental Hospital, the Second Hospital of Xinxiang Medical University, Xinxiang, 453002Henan, China
Z. Zhang
Affiliation:
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, No. 87, DingJiaQiao Road, Nanjing, 210009Jiangsu, PR China Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, 210009Jiangsu, China
C. Xie*
Affiliation:
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, No. 87, DingJiaQiao Road, Nanjing, 210009Jiangsu, PR China Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, 210009Jiangsu, China
*
*Corresponding author. Fax: +86 25 8328 5132. E-mail address:chmxie@163.com (C. Xie).
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Abstract

Background:

The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.

Methods:

Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.

Results:

We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).

Conclusion:

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.

Keywords

Catechol-O-methyltransferaseMajor depressive disorderFunctional connectivity densityDopamineNonlinear modulation
Type
Original article
Information
European Psychiatry , Volume 45 , September 2017 , pp. 6 - 13
Copyright
Copyright © European Psychiatric Association 2017

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Footnotes

1

The authors contribute equally to this article.

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