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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:[email protected] (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.

References

Smith, KMental health: a world of depression. Cah Rev The 2014;515:181.Google Scholar
Sullivan, PFNeale, MCKendler, KSGenetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000;157:1552–1562.CrossRefGoogle Scholar
Consortium, CSparse whole-genome sequencing identifies two loci for major depressive disorder. Cah Rev The 2015;523:588–591.Google Scholar
Hyde, CLNagle, MWTian, CChen, XPaciga, SAWendland, JR, et al.Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat Genet 2016CrossRefGoogle Scholar
Leuchter, AFMcCracken, JTHunter, AMCook, IAAlpert, JEMonoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder. J Clin Psychopharmacol 2009;29:372–377.CrossRefGoogle ScholarPubMed
Won, EHam, BJImaging genetics studies on monoaminergic genes in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2016;64:311–319.CrossRefGoogle ScholarPubMed
Lopez-Leon, SJanssens, ACGonzalez-Zuloeta Ladd, AMDel-Favero, JClaes, SJOostra, BA, et al.Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry 2008;13:772–785.CrossRefGoogle ScholarPubMed
Lambert, GJohansson, MAgren, HFriberg, PReduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry 2000;57:787–793.CrossRefGoogle ScholarPubMed
Leggio, GMSalomone, SBucolo, CPlatania, CMicale, VCaraci, F, et al.Dopamine D(3) receptor as a new pharmacological target for the treatment of depression. Eur J Pharmacol 2013;719:25–33.CrossRefGoogle ScholarPubMed
Opmeer, EMKortekaas, RAleman, ADepression and the role of genes involved in dopamine metabolism and signaling. Prog Neurobiol 2010;92:112–133.CrossRefGoogle Scholar
Männistö, PTKaakkola, SCatechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev 1999;51:593–628.Google ScholarPubMed
Lachman, HMPapolos, DFSaito, TYu, YMSzumlanski, CLWeinshilboum, RMHuman catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenet 1996;6:243–250.CrossRefGoogle ScholarPubMed
Antypa, NDrago, ASerretti, AThe role of COMT gene variants in depression: bridging neuropsychological, behavioral and clinical phenotypes. Neurosci Biobehav Rev 2013;37:1597–1610.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, ANichols, TCallicott, JHDing, JKolachana, BBuckholtz, J, et al.Impact of complex genetic variation in COMT on human brain function. Mol Psychiatry 2006;11:867–877. 797.CrossRefGoogle ScholarPubMed
Mier, DKirsch, PMeyer-Lindenberg, ANeural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Mol Psychiatry 2010;15:918–927.CrossRefGoogle ScholarPubMed
Cools, RD’Esposito, MInverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry 2011;69:e113–e125.CrossRefGoogle ScholarPubMed
Fallon, SJWilliams-Gray, CHBarker, RAOwen, AMHampshire, APrefrontal dopamine levels determine the balance between cognitive stability and flexibility. Cereb Cortex 2013;23:361–369.CrossRefGoogle ScholarPubMed
Bertolino, AFazio, LDi Giorgio, ABlasi, GRomano, RTaurisano, P, et al.Genetically determined interaction between the dopamine transporter and the D2 receptor on prefronto-striatal activity and volume in humans. J Neurosci 2009;29:1224–1234.CrossRefGoogle ScholarPubMed
Rakshi, JSUema, TIto, KBailey, DLMorrish, PKAshburner, J, et al.Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study. Brain 1999;122(Pt 9):1637–1650.CrossRefGoogle Scholar
Seok, JHChoi, SLim, HKLee, SHKim, IHam, BJEffect of the COMT val158met polymorphism on white matter connectivity in patients with major depressive disorder. Neurosci Lett 2013;545:35–39.CrossRefGoogle ScholarPubMed
Watanabe, KKakeda, SYoshimura, RAbe, OIde, SHayashi, K, et al.Relationship between the catechol-O-methyl transferase Val108/158Met genotype and brain volume in treatment-naive major depressive disorder: voxel-based morphometry analysis. Psychiatry Res 2015;233:481–487.CrossRefGoogle ScholarPubMed
Pan, CCMcQuoid, DRTaylor, WDPayne, MEAshley-Koch, ASteffens, DCAssociation analysis of the COMT/MTHFR genes and geriatric depression: an MRI study of the putamen. Int J Geriatr Psychiatry 2009;24:847–855.CrossRefGoogle ScholarPubMed
Hayashi, KYoshimura, RKakeda, SKishi, TAbe, OUmene-Nakano, W, et al.COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naive major depressive disorder: a diffusion tensor imaging study. Neuropsychiatr Dis and Treat 2014;10:1183–1190.Google Scholar
Heinz, ASmolka, MNThe effects of catechol O-methyltransferase genotype on brain activation elicited by affective stimuli and cognitive tasks. Rev Neurosci 2006;17:359–367.CrossRefGoogle ScholarPubMed
Opmeer, EMKortekaas, Rvan Tol, MJvan der Wee, NJWoudstra, Svan Buchem, MA, et al.Influence of COMT val158met genotype on the depressed, brain during emotional processing and working memory. PLoS One 2013;8:e73290.CrossRefGoogle ScholarPubMed
Tomasi, DVolkow, NDFunctional connectivity density mapping. Proc Natl Acad Sci U S A. 2010;107:9885–9890.CrossRefGoogle ScholarPubMed
Tomasi, DVolkow, NDFunctional connectivity hubs in the human brain. Neuroimage 2011;57:908–917.CrossRefGoogle ScholarPubMed
Shen, XWu, YGuan, TWang, XQian, MLin, M, et al.Association analysis of COMT/MTHFR polymorphisms and major depressive disorder in Chinese Han population. J Affect Disord. 2014;161:73–78.CrossRefGoogle ScholarPubMed
Gong, LYin, YHe, CYe, QBai, FYuan, Y, et al.Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder. J Psychiat Res. 2017;84:9–17.CrossRefGoogle ScholarPubMed
Ashburner, JBarnes, GChen, CDaunizeau, JFlandin, GFriston, K, et al.SPM12 Manual. London (UK): Wellcome Trust Centre for Neuroimaging; 2014.Google Scholar
Power, JDBarnes, KASnyder, AZSchlaggar, BLPetersen, SESteps toward optimizing motion artifact removal in functional connectivity MRI; a reply to Carp. Neuroimage 2013;76:439–441.CrossRefGoogle ScholarPubMed
Power, JDBarnes, KASnyder, AZSchlaggar, BLPetersen, SESpurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 2012;59:2142–2154.CrossRefGoogle ScholarPubMed
Zhang, BLi, MQin, WDemenescu, LRMetzger, CDBogerts, B, et al.Altered functional connectivity density in major depressive disorder at rest. Eur Arch Psychiatry Clin Neurosci 2016;266:239–248.CrossRefGoogle ScholarPubMed
Power, JDCohen, ALNelson, SMWig, GSBarnes, KAChurch, JA, et al.Functional network organization of the human brain. Neuron 2011;72:665–678.CrossRefGoogle ScholarPubMed
Aron, ARRobbins, TWPoldrack, RAInhibition and the right inferior frontal cortex: one decade on. Trends Cogn Sci 2014;18:177–185.CrossRefGoogle Scholar
Visser, MLambon Ralph, MADifferential contributions of bilateral ventral anterior temporal lobe and left anterior superior temporal gyrus to semantic processes. J Cogn Neurosci 2011;23:3121–3131.CrossRefGoogle ScholarPubMed
Hamilton, JPFarmer, MFogelman, PGotlib, IHDepressive Rumination, the default-mode network and the dark matter of clinical neuroscience. Biol Psychiatry 2015CrossRefGoogle Scholar
Li, WLiu, BXu, JJiang, TYu, CInteraction of COMT rs4680 and BDNF rs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults. Hum Brain Mapp 2016;37:2468–2478.CrossRefGoogle ScholarPubMed
Honea, RVerchinski, BAPezawas, LKolachana, BSCallicott, JHMattay, VS, et al.Impact of interacting functional variants in COMT on regional gray matter volume in human brain. Neuroimage 2009;45:44–51.CrossRefGoogle ScholarPubMed
Krach, SJansen, AKrug, AMarkov, VThimm, MSheldrick, AJ, et al.COMT genotype and its role on hippocampal-prefrontal regions in declarative memory. Neuroimage 2010;53:978–984.CrossRefGoogle ScholarPubMed
Tian, TQin, WLiu, BJiang, TYu, CFunctional connectivity in healthy subjects is nonlinearly modulated by the COMT and DRD2 polymorphisms in a functional system-dependent manner. J Neurosci 2013;33:17519–17526.CrossRefGoogle Scholar
Vijayraghavan, SWang, MBirnbaum, SGWilliams, GVArnsten, AFInverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci 2007;10:376–384.CrossRefGoogle ScholarPubMed
Dunlop, BWNemeroff, CBThe role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry 2007;64:327–337.CrossRefGoogle ScholarPubMed
Lotta, TVidgren, JTilgmann, CUlmanen, IMelen, KJulkunen, I, et al.Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry-Us 1995;34:4202–4210.CrossRefGoogle ScholarPubMed
Qin, SHelena, CMark, RLuo, JBarbara, FHermans, EJ, et al.The effect of moderate acute psychological stress on working memory-related neural activity is modulated by a genetic variation in catecholaminergic function in humans. Front Integr Neurosci 2012;6:16.CrossRefGoogle ScholarPubMed
Xu, JQin, WLiu, BJiang, TYu, CInteractions of genetic variants reveal inverse modulation patterns of dopamine system on brain gray matter volume and resting-state functional connectivity in healthy young adults. Brain Struct Funct 2016;221:3891–3901.CrossRefGoogle ScholarPubMed
Williams, GVGoldman-Rakic, PSModulation of memory fields by dopamine D1 receptors in prefrontal cortex. Cah Rev The 1995;376:572–575.Google ScholarPubMed
Bertolino, ADi Giorgio, ABlasi, GSambataro, FCaforio, GSinibaldi, L, et al.Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks. Biol Psychiatry 2008;64:226–234.CrossRefGoogle ScholarPubMed
Qin, SCousijn, HRijpkema, MLuo, JFranke, BHermans, EJ, et al.The effect of moderate acute psychological stress on working memory-related neural activity is modulated by a genetic variation in catecholaminergic function in humans. Front Integr Neurosci 2012;6:16.CrossRefGoogle ScholarPubMed
Sambataro, FFazio, LTaurisano, PGelao, BPorcelli, AMancini, M, et al.DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding. Schizophr Bull 2013;39:206–216.CrossRefGoogle ScholarPubMed
Guo, JSimmons, WKHerscovitch, PMartin, AHall, KDStriatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior. Mol Psychiatry 2014;19:1078–1084.CrossRefGoogle ScholarPubMed
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