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Imaging Genetics Studies on Susceptibility Genes for Major Depressive Disorder, the Present and the Future

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Understanding Depression

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Abstract

Although the genetic risk component for major depressive disorder (MDD) is considered to be substantial, genes do not directly encode for psychiatric symptoms. Therefore, intermediate phenotypes of neuroanatomical nature in MDD have been detected by imaging techniques. In order to evaluate the impact of genetic variation on behavior-related psychiatric symptoms, imaging genetics has been applied in various psychiatric disorders. Numerous studies have used magnetic resonance imaging to measure gray matter (GM) structure, white matter (WM) integrity and density, and functional metabolic activity patterns. This paper provides a comprehensive review of currently existing imaging genetics studies on MDD susceptibility gene polymorphisms (BDNF rs6265 (Val66Met), COMT rs4680 (Val158Met), MAOA-uVNTR, HTR1A rs6295 C(–1019)G, 5-HTTLPR, TPH2 rs4570625 (G-703T)), which have measured changes in GM structure, WM integrity, and functional abolic activity patterns of the brain.

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References

  • Ashburner J, Friston KJ. Voxel-based morphometry--the methods. NeuroImage. 2000;11(6 Pt 1):805–21.

    Google Scholar 

  • Bergouignan L, Chupin M, Czechowska Y, Kinkingnehun S, Lemogne C, Le Bastard G, et al. Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression? NeuroImage. 2009;45(1):29–37.

    Google Scholar 

  • Bertolino A, Arciero G, Rubino V, Latorre V, De Candia M, Mazzola V, et al. Variation of human amygdala response during threatening stimuli as a function of 5'HTTLPR genotype and personality style. Biol Psychiatry. 2005;57(12):1517–25.

    Google Scholar 

  • Bigos KL, Weinberger DR. Imaging genetics--days of future past. NeuroImage. 2010;53(3):804–9.

    Google Scholar 

  • Bishop SJ, Cohen JD, Fossella J, Casey BJ, Farah MJ. COMT genotype influences prefrontal response to emotional distraction. Cogn Affect Behav Neurosci. 2006;6(1):62–70.

    Google Scholar 

  • Blakely RD, Ramamoorthy S, Schroeter S, Qian Y, Apparsundaram S, Galli A, et al. Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins. Biol Psychiatry. 1998;44(3):169–78.

    Google Scholar 

  • Blier P. Altered function of the serotonin 1A autoreceptor and the antidepressant response. Neuron. 2010;65(1):1–2.

    Google Scholar 

  • Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, et al. Patterns of brain activation in people at risk for Alzheimer’s disease. N Engl J Med. 2000;343(7):450–6.

    Google Scholar 

  • Bosker FJ, Hartman CA, Nolte IM, Prins BP, Terpstra P, Posthuma D, et al. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry. 2011;16(5):516–32.

    Google Scholar 

  • Boulle F, van den Hove DL, Jakob SB, Rutten BP, Hamon M, van Os J, et al. Epigenetic regulation of the BDNF gene: implications for psychiatric disorders. Mol Psychiatry. 2012;17(6):584–96.

    Google Scholar 

  • Brown SM, Peet E, Manuck SB, Williamson DE, Dahl RE, Ferrell RE, et al. A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Mol Psychiatry. 2005;10(9):884–888., 805.

    Google Scholar 

  • Bueller JA, Aftab M, Sen S, Gomez-Hassan D, Burmeister M, Zubieta JK. BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biol Psychiatry. 2006;59:812–15.

    Google Scholar 

  • Canli T, Congdon E, Gutknecht L, Constable RT, Lesch KP. Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation. J Neural Transm (Vienna). 2005a;112(11):1479–85.

    Google Scholar 

  • Canli T, Omura K, Haas BW, Fallgatter A, Constable RT, Lesch KP. Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task. Proc Natl Acad Sci U S A. 2005b;102(34):12224–9.

    Google Scholar 

  • Canli T, Ferri J, Duman EA. Genetics of emotion regulation. Neuroscience. 2009;164(1):43–54.

    Google Scholar 

  • Castren E. Is mood chemistry? Nat Rev Neurosci. 2005;6(3):241–6.

    Google Scholar 

  • Cerasa A, Gioia MC, Labate A, Lanza P, Magariello A, Muglia M, et al. MAO A VNTR polymorphism and variation in human morphology: a VBM study. Neuroreport. 2008a;19(11):1107–10.

    Google Scholar 

  • Cerasa A, Gioia MC, Labate A, Liguori M, Lanza P, Quattrone A. Impact of catechol-O-methyltransferase Val(108/158) Met genotype on hippocampal and prefrontal gray matter volume. Neuroreport. 2008b;19(4):405–8.

    Google Scholar 

  • Cerasa A, Cherubini A, Quattrone A, Gioia MC, Magariello A, Muglia M, et al. Morphological correlates of MAO A VNTR polymorphism: new evidence from cortical thickness measurement. Behav Brain Res. 2010;211(1):118–24.

    Google Scholar 

  • Cervilla JA, Rivera M, Molina E, Torres-Gonzalez F, Bellon JA, Moreno B, et al. The 5-HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: the PREDICT-gene study. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(8):912–7.

    Google Scholar 

  • Chepenik LG, Fredericks C, Papademetris X, Spencer L, Lacadie C, Wang F, et al. Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder. Neuropsychopharmacology. 2009;34(4):944–51.

    Google Scholar 

  • Chiang MC, Barysheva M, Toga AW, Medland SE, Hansell NK, James MR, et al. BDNF gene effects on brain circuitry replicated in 455 twins. NeuroImage. 2011;55(2):448–54.

    Google Scholar 

  • Choi S, Han KM, Won E, Yoon BJ, Lee MS, Ham BJ. Association of brain-derived neurotrophic factor DNA methylation and reduced white matter integrity in the anterior corona radiata in major depression. J Affect Disord. 2014;172C:74–80.

    Google Scholar 

  • Collier DA, Stober G, Li T, Heils A, Catalano M, Di Bella D, et al. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry. 1996;1(6):453–60.

    Google Scholar 

  • Costafreda SG, McCann P, Saker P, Cole JH, Cohen-Woods S, Farmer AE, et al. Modulation of amygdala response and connectivity in depression by serotonin transporter polymorphism and diagnosis. J Affect Disord. 2013;150(1):96–103

    Google Scholar 

  • Dannlowski U, Ohrmann P, Bauer J, Kugel H, Baune BT, Hohoff C, et al. Serotonergic genes modulate amygdala activity in major depression. Genes Brain Behav. 2007;6(7):672–6.

    Google Scholar 

  • Dannlowski U, Ohrmann P, Bauer J, Deckert J, Hohoff C, Kugel H, et al. 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology. 2008;33(2):418–24.

    Google Scholar 

  • Dannlowski U, Konrad C, Kugel H, Zwitserlood P, Domschke K, Schoning S, et al. Emotion specific modulation of automatic amygdala responses by 5-HTTLPR genotype. NeuroImage. 2010;53(3):893–8.

    Google Scholar 

  • Dannlowski U, Kugel H, Redlich R, Halik A, Schneider I, Opel N, et al. Serotonin transporter gene methylation is associated with hippocampal gray matter volume. Hum Brain Mapp. 2014;35(11):5356–67.

    Google Scholar 

  • Dannlowski U, Grabe HJ, Wittfeld K, Klaus J, Konrad C, Grotegerd D, et al. Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure. Mol Psychiatry. 2015;20(3):398–404.

    Google Scholar 

  • Denson TF, Dobson-Stone C, Ronay R, von Hippel W, Schira MM. A functional polymorphism of the MAOA gene is associated with neural responses to induced anger control. J Cogn Neurosci. 2014;26(7):1418–27.

    Google Scholar 

  • Domschke K, Baune BT, Havlik L, Stuhrmann A, Suslow T, Kugel H, et al. Catechol-O-methyltransferase gene variation: impact on amygdala response to aversive stimuli. NeuroImage. 2012;60(4):2222–9.

    Google Scholar 

  • Drabant EM, Hariri AR, Meyer-Lindenberg A, Munoz KE, Mattay VS, Kolachana BS, et al. Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Arch Gen Psychiatry. 2006;63(12):1396–406.

    Google Scholar 

  • Dreher JC, Kohn P, Kolachana B, Weinberger DR, Berman KF. Variation in dopamine genes influences responsivity of the human reward system. Proc Natl Acad Sci U S A. 2009;106(2):617–22.

    Google Scholar 

  • Duman RS. Role of neurotrophic factors in the etiology and treatment of mood disorders. NeuroMolecular Med. 2004;5(1):11–25.

    Google Scholar 

  • Dunlop BW, Mayberg HS. Neuroimaging-based biomarkers for treatment selection in major depressive disorder. Dialogues Clin Neurosci. 2014;16(4):479–90.

    Google Scholar 

  • Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001;98(12):6917–22.

    Google Scholar 

  • Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112(2):257–69.

    Google Scholar 

  • Ehrlich S, Morrow EM, Roffman JL, Wallace SR, Naylor M, Bockholt HJ, et al. The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults. NeuroImage. 2010;53(3):992–1000.

    Google Scholar 

  • Fakra E, Hyde LW, Gorka A, Fisher PM, Munoz KE, Kimak M, et al. Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. Arch Gen Psychiatry. 2009;66(1):33–40.

    Google Scholar 

  • Fisher PM, Meltzer CC, Ziolko SK, Price JC, Moses-Kolko EL, Berga SL, et al. Capacity for 5-HT1A-mediated autoregulation predicts amygdala reactivity. Nat Neurosci. 2006;9(11):1362–3.

    Google Scholar 

  • Fjell AM, Walhovd KB. Structural brain changes in aging: courses, causes and cognitive consequences. Rev Neurosci. 2010;21(3):187–221.

    Google Scholar 

  • Frodl T, Schule C, Schmitt G, Born C, Baghai T, Zill P, et al. Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry. 2007;64(4):410–6.

    Google Scholar 

  • Frodl T, Koutsouleris N, Bottlender R, Born C, Jager M, Morgenthaler M, et al. Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression. Mol Psychiatry. 2008;13(12):1093–101.

    Google Scholar 

  • Frodl T, Reinhold E, Koutsouleris N, Donohoe G, Bondy B, Reiser M, et al. Childhood stress, serotonin transporter gene and brain structures in major depression. Neuropsychopharmacology. 2010;35(6):1383–90.

    Google Scholar 

  • Furlong RA, Ho L, Walsh C, Rubinsztein JS, Jain S, Paykel ES, et al. Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders. Am J Med Genet. 1998;81(1):58–63.

    Google Scholar 

  • Furman DJ, Hamilton JP, Joormann J, Gotlib IH. Altered timing of amygdala activation during sad mood elaboration as a function of 5-HTTLPR. Soc Cogn Affect Neurosci. 2011;6(3):270–76.

    Google Scholar 

  • Gao J, Pan Z, Jiao Z, Li F, Zhao G, Wei Q, et al. TPH2 gene polymorphisms and major depression--a meta-analysis. PLoS One. 2012;7(5):e36721.

    Google Scholar 

  • Garris PA, Wightman RM. Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum: an in vivo voltammetric study. J Neurosci. 1994;14(1):442–50.

    Google Scholar 

  • Gillihan SJ, Rao H, Wang J, Detre JA, Breland J, Sankoorikal GM, et al. Serotonin transporter genotype modulates amygdala activity during mood regulation. Soc Cogn Affect Neurosci. 2010;5(1):1–10.

    Google Scholar 

  • Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003;160(4):636–45.

    Google Scholar 

  • Grieve SM, Korgaonkar MS, Koslow SH, Gordon E, Williams LM. Widespread reductions in gray matter volume in depression. Neuroimage Clin. 2013;3:332–9.

    Google Scholar 

  • Gutknecht L, Jacob C, Strobel A, Kriegebaum C, Muller J, Zeng Y, et al. Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation. Int J Neuropsychopharmacol. 2007;10(3):309–20.

    Google Scholar 

  • Han X, Jovicich J, Salat D, van der Kouwe A, Quinn B, Czanner S, et al. Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer. NeuroImage. 2006;32(1):180–94.

    Google Scholar 

  • Hariri AR, Weinberger DR. Imaging genomics. Br Med Bull. 2003;65:259–70.

    Google Scholar 

  • Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science. 2002;297(5580):400–3.

    Google Scholar 

  • Hariri AR, Goldberg TE, Mattay VS, Kolachana BS, Callicott JH, Egan MF, et al. Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci. 2003;23(17):6690–4.

    Google Scholar 

  • Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, et al. A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry. 2005;62(2):146–52.

    Google Scholar 

  • Hariri AR, Drabant EM, Weinberger DR. Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biol Psychiatry. 2006;59(10):888–97.

    Google Scholar 

  • Hashimoto R, Moriguchi Y, Yamashita F, Mori T, Nemoto K, Okada T, et al. Dose-dependent effect of the Val66Met polymorphism of the brain-derived neurotrophic factor gene on memory-related hippocampal activity. Neurosci Res. 2008;61(4):360–7.

    Google Scholar 

  • Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem. 1996;66(6):2621–4.

    Google Scholar 

  • Heinz A, Braus DF, Smolka MN, Wrase J, Puls I, Hermann D, et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci. 2005;8(1):20–1.

    Google Scholar 

  • Hilgetag CC, Barbas H. Role of mechanical factors in the morphology of the primate cerebral cortex. PLoS Comput Biol. 2006;2(3):e22.

    Google Scholar 

  • Honea R, Verchinski BA, Pezawas L, Kolachana BS, Callicott JH, Mattay VS, et al. Impact of interacting functional variants in COMT on regional gray matter volume in human brain. NeuroImage. 2009;45(1):44–51.

    Google Scholar 

  • Huang SY, Lin MT, Lin WW, Huang CC, Shy MJ, Lu RB. Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population. World J Biol Psychiatry. 2009;10(4 Pt 2):544–51.

    Google Scholar 

  • Huettel SA, Song AW, McCarthy G. Decisions under uncertainty: probabilistic context influences activation of prefrontal and parietal cortices. J Neurosci. 2005;25(13):3304–11.

    Google Scholar 

  • Inoue H, Yamasue H, Tochigi M, Takei K, Suga M, Abe O, et al. Effect of tryptophan hydroxylase-2 gene variants on amygdalar and hippocampal volumes. Brain Res. 2010;1331:51–7.

    Google Scholar 

  • Jung J, Kang J, Won E, Nam K, Lee MS, Tae WS, et al. Impact of lingual gyrus volume on antidepressant response and neurocognitive functions in Major Depressive Disorder: a voxel-based morphometry study. J Affect Disord. 2014;169:179–87.

    Google Scholar 

  • Kempton MJ, Haldane M, Jogia J, Christodoulou T, Powell J, Collier D, et al. The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study. Int J Neuropsychopharmacol. 2009;12(3):371–81.

    Google Scholar 

  • Kieseppa T, Eerola M, Mantyla R, Neuvonen T, Poutanen VP, Luoma K, et al. Major depressive disorder and white matter abnormalities: a diffusion tensor imaging study with tract-based spatial statistics. J Affect Disord. 2010;120(1–3):240–4.

    Google Scholar 

  • Kobilka BK, Frielle T, Collins S, Yang-Feng T, Kobilka TS, Francke U, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature. 1987;329(6134):75–9.

    Google Scholar 

  • Kohli MA, Lucae S, Saemann PG, Schmidt MV, Demirkan A, Hek K, et al. The neuronal transporter gene SLC6A15 confers risk to major depression. Neuron. 2011;70(2):252–65.

    Google Scholar 

  • Konarski JZ, McIntyre RS, Kennedy SH, Rafi-Tari S, Soczynska JK, Ketter TA. Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder. Bipolar Disord. 2008;10(1):1–37.

    Google Scholar 

  • Krach S, Jansen A, Krug A, Markov V, Thimm M, Sheldrick AJ, et al. COMT genotype and its role on hippocampal-prefrontal regions in declarative memory. NeuroImage. 2010;53(3):978–84.

    Google Scholar 

  • Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008;455(7215):894–902.

    Google Scholar 

  • Lai CH. Gray matter volume in major depressive disorder: a meta-analysis of voxel-based morphometry studies. Psychiatry Res. 2013;211(1):37–46.

    Google Scholar 

  • Lai CH, Wu YT. Frontal-insula gray matter deficits in first-episode medication-naive patients with major depressive disorder. J Affect Disord. 2014;160:74–9.

    Google Scholar 

  • Lang UE, Hellweg R, Kalus P, Bajbouj M, Lenzen KP, Sander T, et al. Association of a functional BDNF polymorphism and anxiety-related personality traits. Psychopharmacology. 2005;180(1):95–9.

    Google Scholar 

  • Lau JY, Goldman D, Buzas B, Hodgkinson C, Leibenluft E, Nelson E, et al. BDNF gene polymorphism (Val66Met) predicts amygdala and anterior hippocampus responses to emotional faces in anxious and depressed adolescents. NeuroImage. 2010;53(3):952–61.

    Google Scholar 

  • Lee BT, Ham BJ. Monoamine oxidase A-uVNTR genotype affects limbic brain activity in response to affective facial stimuli. Neuroreport. 2008a;19(5):515–9.

    Google Scholar 

  • Lee BT, Ham BJ. Serotonergic genes and amygdala activity in response to negative affective facial stimuli in Korean women. Genes Brain Behav. 2008b;7(8):899–905.

    Google Scholar 

  • Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, et al. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci. 2003;23(25):8788–99.

    Google Scholar 

  • Lesch KP, Balling U, Gross J, Strauss K, Wolozin BL, Murphy DL, et al. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect. 1994;95(2):157–62.

    Google Scholar 

  • Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996;274(5292):1527–31.

    Google Scholar 

  • Lim HK, Jung WS, Ahn KJ, Won WY, Hahn C, Lee SY, et al. Regional cortical thickness and subcortical volume changes are associated with cognitive impairments in the drug-naive patients with late-onset depression. Neuropsychopharmacology. 2012;37(3):838–49.

    Google Scholar 

  • Little K, Olsson CA, Whittle S, Youssef GJ, Byrne ML, Simmons JG, et al. Association between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study. Transl Psychiatry. 2014;4:e445.

    Google Scholar 

  • Lohoff FW. Overview of the genetics of major depressive disorder. Curr Psychiatry Rep. 2010;12(6):539–46.

    Google Scholar 

  • Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen 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. 1995;34(13):4202–10.

    Google Scholar 

  • Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci. 2005;6(8):603–14.

    Google Scholar 

  • Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990;247(4949 Pt 1):1446–51.

    Google Scholar 

  • Martinowich K, Manji H, Lu B. New insights into BDNF function in depression and anxiety. Nat Neurosci. 2007;10(9):1089–93.

    Google Scholar 

  • Matsuo K, Walss-Bass C, Nery FG, Nicoletti MA, Hatch JP, Frey BN, et al. Neuronal correlates of brain-derived neurotrophic factor Val66Met polymorphism and morphometric abnormalities in bipolar disorder. Neuropsychopharmacology. 2009;34(8):1904–13.

    Google Scholar 

  • Melas PA, Wei Y, Wong CC, Sjoholm LK, Aberg E, Mill J, et al. Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. Int J Neuropsychopharmacol. 2013;16(7):1513–28.

    Google Scholar 

  • Meyer-Lindenberg A. Intermediate or brainless phenotypes for psychiatric research? Psychol Med. 2010;40(7):1057–62.

    Google Scholar 

  • Meyer-Lindenberg A, Weinberger DR. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci. 2006;7(10):818–27.

    Google Scholar 

  • Meyer-Lindenberg A, Buckholtz JW, Kolachana B, Hariri AR, Pezawas L, Blasi G, et al. Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci U S A. 2006;103(16):6269–74.

    Google Scholar 

  • Michaelovsky E, Frisch A, Rockah R, Peleg L, Magal N, Shohat M, et al. A novel allele in the promoter region of the human serotonin transporter gene. Mol Psychiatry. 1999;4(1):97–9.

    Google Scholar 

  • Montag C, Reuter M, Newport B, Elger C, Weber B. The BDNF Val66Met polymorphism affects amygdala activity in response to emotional stimuli: evidence from a genetic imaging study. NeuroImage. 2008;42(4):1554–9.

    Google Scholar 

  • Montag C, Weber B, Fliessbach K, Elger C, Reuter M. The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression. Psychol Med. 2009;39(11):1831–9.

    Google Scholar 

  • Murphy ML, Frodl T. Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression. Biol Mood Anxiety Disord. 2011;1(1):3.

    Google Scholar 

  • Na KS, Chang HS, Won E, Han KM, Choi S, Tae WS, et al. Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PLoS One. 2014;9(1):e85425.

    Google Scholar 

  • Nemoto K1, Ohnishi T, Mori T, Moriguchi Y, Hashimoto R, Asada T, Kunugi H. The Val66Met polymorphism of the brain-derived neurotrophic factor gene affects age-related brain morphology. Neurosci Lett. 2006;397(1–2):25–9. Epub 2006 Jan 18.

    Google Scholar 

  • Nikolova YS, Koenen KC, Galea S, Wang CM, Seney ML, Sibille E, et al. Beyond genotype: serotonin transporter epigenetic modification predicts human brain function. Nat Neurosci. 2014;17(9):1153–5.

    Google Scholar 

  • Ohara K, Nagai M, Suzuki Y, Ohara K. Low activity allele of catechol-o-methyltransferase gene and Japanese unipolar depression. Neuroreport. 1998;9(7):1305–8.

    Google Scholar 

  • Opmeer EM, Kortekaas R, van Tol MJ, van der Wee NJ, Woudstra S, van Buchem MA, et al. Influence of COMT val158met genotype on the depressed brain during emotional processing and working memory. PLoS One. 2013;8(9):e73290.

    Google Scholar 

  • Oswald P, Del-Favero J, Massat I, Souery D, Claes S, Van Broeckhoven C, et al. No implication of brain-derived neurotrophic factor (BDNF) gene in unipolar affective disorder: evidence from Belgian first and replication patient-control studies. Eur Neuropsychopharmacol. 2005;15(5):491–5.

    Google Scholar 

  • Pezawas L, Meyer-Lindenberg A. Imaging genetics: progressing by leaps and bounds. NeuroImage. 2010;53(3):801–3.

    Google Scholar 

  • Pezawas L, Verchinski BA, Mattay VS, Callicott JH, Kolachana BS, Straub RE, et al. The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci. 2004;24(45):10099–102.

    Google Scholar 

  • Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci. 2005;8(6):828–34.

    Google Scholar 

  • Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron. 2005;48(2):175–87.

    Google Scholar 

  • Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology. 2010;35(1):192–216.

    Google Scholar 

  • Price JS, Strong J, Eliassen J, McQueeny T, Miller M, Padula CB, et al. Serotonin transporter gene moderates associations between mood, memory and hippocampal volume. Behav Brain Res. 2013;242:158–65.

    Google Scholar 

  • Psychiatric GWAS Consortium Coordinating Committee, Cichon S, Craddock N, Daly M, Faraone SV, Gejman PV, et al. Genomewide association studies: history, rationale, and prospects for psychiatric disorders. Am J Psychiatry. 2009;166(5):540–56.

    Google Scholar 

  • Rabl U, Meyer BM, Diers K, Bartova L, Berger A, Mandorfer D, et al. Additive gene-environment effects on hippocampal structure in healthy humans. J Neurosci. 2014;34(30):9917–26.

    Google Scholar 

  • Ramasubbu R, Tobias R, Buchan AM, Bech-Hansen NT. Serotonin transporter gene promoter region polymorphism associated with poststroke major depression. J Neuropsychiatry Clin Neurosci. 2006;18(1):96–9.

    Google Scholar 

  • Rasch B, Spalek K, Buholzer S, Luechinger R, Boesiger P, de Quervain DJ, et al. Aversive stimuli lead to differential amygdala activation and connectivity patterns depending on catechol-O-methyltransferase Val158Met genotype. NeuroImage. 2010;52(4):1712–9.

    Google Scholar 

  • Roberts RE, Anderson EJ, Husain M. White matter microstructure and cognitive function. Neuroscientist. 2013;19(1):8–15.

    Google Scholar 

  • Rothe C, Gutknecht L, Freitag C, Tauber R, Mossner R, Franke P, et al. Association of a functional 1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia. Int J Neuropsychopharmacol. 2004;7(2):189–92.

    Google Scholar 

  • Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet. 1998;103(3):273–9.

    Google Scholar 

  • Scharinger C, Rabl U, Sitte HH, Pezawas L. Imaging genetics of mood disorders. NeuroImage. 2010;53(3):810–21.

    Google Scholar 

  • Schofield PR, Williams LM, Paul RH, Gatt JM, Brown K, Luty A, et al. Disturbances in selective information processing associated with the BDNF Val66Met polymorphism: evidence from cognition, the P300 and fronto-hippocampal systems. Biol Psychol. 2009;80(2):176–88.

    Google Scholar 

  • Scott ML, Bromiley PA, Thacker NA, Hutchinson CE, Jackson A. A fast, model-independent method for cerebral cortical thickness estimation using MRI. Med Image Anal. 2009;13(2):269–85.

    Google Scholar 

  • Sen S, Nesse RM, Stoltenberg SF, Li S, Gleiberman L, Chakravarti A, et al. A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology. 2003;28(2):397–401.

    Google Scholar 

  • Seok JH, Choi S, Lim HK, Lee SH, Kim I, Ham BJ. Effect of the COMT val158met polymorphism on white matter connectivity in patients with major depressive disorder. Neurosci Lett. 2013;545:35–9.

    Google Scholar 

  • Serretti A, Cristina S, Lilli R, Cusin C, Lattuada E, Lorenzi C, et al. Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders. Am J Med Genet. 2002;114(4):361–9.

    Google Scholar 

  • Serretti A, Artioli P, Lorenzi C, Pirovano A, Tubazio V, Zanardi R. The C(-1019)G polymorphism of the 5-HT1A gene promoter and antidepressant response in mood disorders: preliminary findings. Int J Neuropsychopharmacol. 2004;7(4):453–60.

    Google Scholar 

  • Serretti A, Kato M, De Ronchi D, Kinoshita T. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Mol Psychiatry. 2007;12(3):247–57.

    Google Scholar 

  • Shah PJ, Ebmeier KP, Glabus MF, Goodwin GM. Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. Br J Psychiatry. 1998;172:527–32.

    Google Scholar 

  • Shaw P, Wallace GL, Addington A, Evans A, Rapoport J, Giedd JN. Effects of the Val158Met catechol-O-methyltransferase polymorphism on cortical structure in children and adolescents. Mol Psychiatry. 2009;14(4):348–9.

    Google Scholar 

  • Smolka MN, Schumann G, Wrase J, Grusser SM, Flor H, Mann K, et al. Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J Neurosci. 2005;25(4):836–42.

    Google Scholar 

  • Stahl S. 5HT1A receptors and pharmacotherapy. Is serotonin receptor down-regulation linked to the mechanism of action of antidepressant drugs? Psychopharmacol Bull. 1994;30(1):39–43.

    Google Scholar 

  • Stober G, Heils A, Lesch KP. Serotonin transporter gene polymorphism and affective disorder. Lancet. 1996;347(9011):1340–1.

    Google Scholar 

  • Stratmann M, Konrad C, Kugel H, Krug A, Schoning S, Ohrmann P, et al. Insular and hippocampal gray matter volume reductions in patients with major depressive disorder. PLoS One. 2014;9(7):e102692.

    Google Scholar 

  • Strauss J, Barr CL, George CJ, Devlin B, Vetro A, Kiss E, et al. Brain-derived neurotrophic factor variants are associated with childhood-onset mood disorder: confirmation in a Hungarian sample. Mol Psychiatry. 2005;10(9):861–7.

    Google Scholar 

  • Strobel A, Gutknecht L, Rothe C, Reif A, Mossner R, Zeng Y, et al. Allelic variation in 5-HT1A receptor expression is associated with anxiety- and depression-related personality traits. J Neural Transm (Vienna). 2003;110(12):1445–53.

    Google Scholar 

  • Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552–62.

    Google Scholar 

  • Surtees PG, Wainwright NW, Willis-Owen SA, Sandhu MS, Luben R, Day NE, et al. No association between the BDNF Val66Met polymorphism and mood status in a non-clinical community sample of 7389 older adults. J Psychiatr Res. 2007;41(5):404–9.

    Google Scholar 

  • Szeszko PR, Lipsky R, Mentschel C, Robinson D, Gunduz-Bruce H, Sevy S, et al. Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry. 2005;10(7):631–6.

    Google Scholar 

  • Taki Y, Kinomura S, Awata S, Inoue K, Sato K, Ito H, et al. Male elderly subthreshold depression patients have smaller volume of medial part of prefrontal cortex and precentral gyrus compared with age-matched normal subjects: a voxel-based morphometry. J Affect Disord. 2005;88(3):313–20.

    Google Scholar 

  • Tang Y, Wang F, Xie G, Liu J, Li L, Su L, et al. Reduced ventral anterior cingulate and amygdala volumes in medication-naive females with major depressive disorder: a voxel-based morphometric magnetic resonance imaging study. Psychiatry Res. 2007;156(1):83–6.

    Google Scholar 

  • Taylor WD, Zuchner S, Payne ME, Messer DF, Doty TJ, MacFall JR, et al. The COMT Val158Met polymorphism and temporal lobe morphometry in healthy adults. Psychiatry Res. 2007;155(2):173–7.

    Google Scholar 

  • Thomason ME, Dougherty RF, Colich NL, Perry LM, Rykhlevskaia EI, Louro HM, et al. COMT genotype affects prefrontal white matter pathways in children and adolescents. NeuroImage. 2010;53(3):926–34.

    Google Scholar 

  • Torgersen S. Genetics of somatoform disorders. Arch Gen Psychiatry. 1986;43(5):502–5.

    Google Scholar 

  • Tost H, Alam T, Geramita M, Rebsch C, Kolachana B, Dickinson D, et al. Effects of the BDNF Val66Met polymorphism on white matter microstructure in healthy adults. Neuropsychopharmacology. 2013;38(3):525–32.

    Google Scholar 

  • Tu PC, Chen LF, Hsieh JC, Bai YM, Li CT, Su TP. Regional cortical thinning in patients with major depressive disorder: a surface-based morphometry study. Psychiatry Res. 2012;202(3):206–13.

    Google Scholar 

  • Vasic N, Walter H, Hose A, Wolf RC. Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study. J Affect Disord. 2008;109(1–2):107–16.

    Google Scholar 

  • Verhagen M, van der Meij A, van Deurzen PA, Janzing JG, Arias-Vasquez A, Buitelaar JK, et al. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol Psychiatry. 2010;15(3):260–71.

    Google Scholar 

  • Wagner G, Schultz CC, Koch K, Schachtzabel C, Sauer H, Schlosser RG. Prefrontal cortical thickness in depressed patients with high-risk for suicidal behavior. J Psychiatr Res. 2012;46(11):1449–55.

    Google Scholar 

  • Wang Y, Li J, Chen C, Chen C, Zhu B, Moysis RK, et al. COMT rs4680 Met is not always the ‘smart allele’: Val allele is associated with better working memory and larger hippocampal volume in healthy Chinese. Genes Brain Behav. 2013;12(3):323–9.

    Google Scholar 

  • Weinberger DR, Mattay V, Callicott J, Kotrla K, Santha A, van Gelderen P, et al. fMRI applications in schizophrenia research. NeuroImage. 1996;4(3 Pt 3):S118–26.

    Google Scholar 

  • Weyler W, Hsu YP, Breakefield XO. Biochemistry and genetics of monoamine oxidase. Pharmacol Ther. 1990;47(3):391–417.

    Google Scholar 

  • Williams LM, Gatt JM, Kuan SA, Dobson-Stone C, Palmer DM, Paul RH, et al. A polymorphism of the MAOA gene is associated with emotional brain markers and personality traits on an antisocial index. Neuropsychopharmacology. 2009;34(7):1797–809.

    Google Scholar 

  • Williams LM, Gatt JM, Grieve SM, Dobson-Stone C, Paul RH, Gordon E, et al. COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias. NeuroImage. 2010;53(3):918–25.

    Google Scholar 

  • Winkler AM, Kochunov P, Blangero J, Almasy L, Zilles K, Fox PT, et al. Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies. NeuroImage. 2010;53(3):1135–46.

    Google Scholar 

  • Won E, Ham BJ. Imaging genetics studies on monoaminergic genes in major depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;64:311–9.

    Google Scholar 

  • Won E, Choi S, Kang J, Kim A, Han KM, Chang HS, et al. Association between reduced white matter integrity in the corpus callosum and serotonin transporter gene DNA methylation in medication-naive patients with major depressive disorder. Transl Psychiatry. 2016a;6(8):e866.

    Google Scholar 

  • Won E, Choi S, Kang J, Lee MS, Ham BJ. Regional cortical thinning of the orbitofrontal cortex in medication-naive female patients with major depressive disorder is not associated with MAOA-uVNTR polymorphism. Ann General Psychiatry. 2016b;15:26.

    Google Scholar 

  • Wu S, Comings DE. A common C-1018G polymorphism in the human 5-HT1A receptor gene. Psychiatr Genet. 1999;9(2):105–6.

    Google Scholar 

  • Yoon HK, Lee HJ, Kim L, Lee MS, Ham BJ. Impact of tryptophan hydroxylase 2 G-703T polymorphism on anger-related personality traits and orbitofrontal cortex. Behav Brain Res. 2012;231(1):105–10.

    Google Scholar 

  • Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW. Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropsychopharmacology. 2005;30(9):1719–23.

    Google Scholar 

  • Zhang J, Chen Y, Zhang K, Yang H, Sun Y, Fang Y, et al. A cis-phase interaction study of genetic variants within the MAOA gene in major depressive disorder. Biol Psychiatry. 2010;68(9):795–800.

    Google Scholar 

  • Ziegler C, Dannlowski U, Brauer D, Stevens S, Laeger I, Wittmann H, et al. Oxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety. Neuropsychopharmacology. 2015;40(6):1528–38.

    Google Scholar 

  • Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240–3.

    Google Scholar 

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  1. Department of Psychiatry, College of Medicine, Korea University, Seoul, South Korea

    Eunsoo Won, Byung Joo Ham & Yong-Ku Kim

  2. Department of Psychiatry, Korea University Ansan Hospital, College of Medicine, Ansan, South Korea

    Yong-Ku Kim

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Won, E., Ham, B.J., Kim, YK. (2018). Imaging Genetics Studies on Susceptibility Genes for Major Depressive Disorder, the Present and the Future. In: Kim, YK. (eds) Understanding Depression . Springer, Singapore. https://doi.org/10.1007/978-981-10-6580-4_2

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