Imaging genetics of mood disorders

Mood disorders are highly heritable and have been linked to brain regions of emotion processing. Over the past few years, an enormous amount of imaging genetics studies has demonstrated the impact of risk genes on brain regions and systems of emotion processing in vivo in healthy subjects as well as in mood disorder patients. While sufficient evidence already exists for several monaminergic genes as well as for a few non-monoaminergic genes, such as brain-derived neurotrophic factor (BDNF) in healthy subjects, many others only have been investigated in single studies so far. Apart from these studies, the present review also covers imaging genetics studies applying more complex genetic disease models of mood disorders, such as epistasis and gene-environment interactions, and their impact on brain systems of emotion processing. This review attempts to provide a comprehensive overview of the rapidly growing field of imaging genetics studies in mood disorder research.

[1]  Stephan Eliez,et al.  Reduced size of the amygdala in individuals with 47,XXY and 47,XXX karyotypes. , 2002, American journal of medical genetics.

[2]  Byung-Joo Ham,et al.  Monoamine oxidase A–uVNTR genotype affects limbic brain activity in response to affective facial stimuli , 2008, Neuroreport.

[3]  J. Duncan,et al.  Effects of the Brain-Derived Neurotrophic Growth Factor Val66Met Variation on Hippocampus Morphology in Bipolar Disorder , 2009, Neuropsychopharmacology.

[4]  A. Caspi,et al.  Role of Genotype in the Cycle of Violence in Maltreated Children , 2002, Science.

[5]  A. Meyer-Lindenberg,et al.  Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis , 2010, Molecular Psychiatry.

[6]  Kazuhiko Yanai,et al.  Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention , 2009, NeuroImage.

[7]  S. Cichon,et al.  Meta-analysis of two genome-wide association studies of bipolar disorder reveals important points of agreement , 2008, Molecular Psychiatry.

[8]  Eliza Congdon,et al.  Additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing , 2008, Biological Psychology.

[9]  R. Busch,et al.  A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety , 2004, Molecular Psychiatry.

[10]  Scott J. Russo,et al.  Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions , 2007, Cell.

[11]  C Poupon,et al.  Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex , 2007, Molecular Psychiatry.

[12]  Antonio Cerasa,et al.  MAO A VNTR polymorphism and variation in human morphology: a VBM study , 2008, Neuroreport.

[13]  M. Egan,et al.  Serotonin Transporter Genetic Variation and the Response of the Human Amygdala , 2002, Science.

[14]  Sarah Durston,et al.  Imaging genetics in ADHD , 2010, NeuroImage.

[15]  M. Wong,et al.  Research and treatment approaches to depression , 2001, Nature Reviews Neuroscience.

[16]  Giuseppe Blasi,et al.  Neural mechanisms of genetic risk for impulsivity and violence in humans. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Andrew Simmons,et al.  Influence of X Chromosome and Hormones on Human Brain Development: A Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy Study of Turner Syndrome , 2006, Biological Psychiatry.

[18]  A. Hariri,et al.  Capacity for 5-HT1A–mediated autoregulation predicts amygdala reactivity , 2006, Nature Neuroscience.

[19]  M. Munafo,et al.  Gene × Environment Interactions at the Serotonin Transporter Locus , 2009, Biological Psychiatry.

[20]  N. Freimer,et al.  5‐HTTLPR genotype and anxiety‐related personality traits: A meta‐analysis and new data , 2009, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[21]  Janice M. Fullerton,et al.  The Val66Met Coding Variant of the Brain-Derived Neurotrophic Factor (BDNF) Gene Does Not Contribute Toward Variation in the Personality Trait Neuroticism , 2005, Biological Psychiatry.

[22]  Dennis L. Murphy,et al.  Targeting the murine serotonin transporter: insights into human neurobiology , 2008, Nature Reviews Neuroscience.

[23]  Martin P Paulus,et al.  Influence of RGS2 on anxiety-related temperament, personality, and brain function. , 2008, Archives of general psychiatry.

[24]  Martha J. Farah,et al.  COMT genotype influences prefrontal response to emotional distraction , 2006, Cognitive, affective & behavioral neuroscience.

[25]  K. Ressler,et al.  Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic , 2007, Nature Neuroscience.

[26]  Timothy Edward John Behrens,et al.  New approaches for exploring anatomical and functional connectivity in the human brain , 2004, Biological Psychiatry.

[27]  N. Risch,et al.  Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. , 2009, JAMA.

[28]  Huda Akil,et al.  Neural circuits mediating stress , 1999, Biological Psychiatry.

[29]  Andrew J. Saykin,et al.  Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimer's Disease , 2009, PloS one.

[30]  Thomas E. Nichols,et al.  Pathway-based approaches to imaging genetics association studies: Wnt signaling, GSK3beta substrates and major depression , 2010, NeuroImage.

[31]  C. Ecker,et al.  Genetic variation in the serotonin transporter modulates neural system‐wide response to fearful faces , 2008, Genes, brain, and behavior.

[32]  K. Lesch,et al.  Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Lukas Scheef,et al.  No association of the Val66Met polymorphism of the brain-derived neurotrophic factor with hippocampal volume in major depression , 2009, Psychiatric genetics.

[34]  Ahmad R. Hariri,et al.  Genetic variation in human NPY expression affects stress response and emotion , 2008, Nature.

[35]  Ahmad R. Hariri,et al.  Human Choline Transporter Gene Variation Is Associated with Corticolimbic Reactivity and Autonomic-Cholinergic Function , 2006, Biological Psychiatry.

[36]  S. Cichon,et al.  Neural Mechanisms of a Genome-Wide Supported Psychosis Variant , 2009, Science.

[37]  H. Flor,et al.  Gene–gene effects on central processing of aversive stimuli , 2007, Molecular Psychiatry.

[38]  M A Rogers,et al.  Association between mitochondrial DNA 10398A>G polymorphism and the volume of amygdala , 2008, Genes, brain, and behavior.

[39]  Michael Davis,et al.  The amygdala , 2000, Current Biology.

[40]  A. Meyer-Lindenberg,et al.  Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Stephan Ripke,et al.  A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression. , 2009, Archives of general psychiatry.

[42]  Marcello Cadioli,et al.  Neural and genetic correlates of antidepressant response to sleep deprivation: a functional magnetic resonance imaging study of moral valence decision in bipolar depression. , 2007, Archives of general psychiatry.

[43]  M. Taylor,et al.  Evidence That Increased 5-HT Release Evokes Region-Specific Effects on Blood-Oxygenation Level-Dependent Functional Magnetic Resonance Imaging Responses in the Rat Brain , 2009, Neuroscience.

[44]  Jordan Grafman,et al.  The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex , 2009, Behavioural Brain Research.

[45]  D. Kumaran,et al.  A Genetically Mediated Bias in Decision Making Driven by Failure of Amygdala Control , 2009, The Journal of Neuroscience.

[46]  C. Siao,et al.  Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior , 2006, Science.

[47]  Henrik Walter,et al.  Volition diminishes genetically mediated amygdala hyperreactivity , 2010, NeuroImage.

[48]  M. Egan,et al.  Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. , 2004, American journal of human genetics.

[49]  H. Möller,et al.  Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression , 2008, Molecular Psychiatry.

[50]  Yong He,et al.  Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder , 2009, Biological Psychiatry.

[51]  R. Burwell.  The Parahippocampal Region: Corticocortical Connectivity , 2000, Annals of the New York Academy of Sciences.

[52]  Karine Sergerie,et al.  The role of the amygdala in emotional processing: A quantitative meta-analysis of functional neuroimaging studies , 2008, Neuroscience & Biobehavioral Reviews.

[53]  A. Caspi,et al.  Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene , 2003, Science.

[54]  Leanne M Williams,et al.  Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness , 2009, Human brain mapping.

[55]  Margit Burmeister,et al.  A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression , 2003, Neuropsychopharmacology.

[56]  Christian Montag,et al.  The BDNF Val66Met polymorphism affects amygdala activity in response to emotional stimuli: Evidence from a genetic imaging study , 2008, NeuroImage.

[57]  R. T. Constable,et al.  Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation , 2005, Journal of Neural Transmission.

[58]  E. Bramon,et al.  Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. , 2004, Archives of general psychiatry.

[59]  A. David,et al.  Predictors of amygdala activation during the processing of emotional stimuli: A meta-analysis of 385 PET and fMRI studies , 2008, Brain Research Reviews.

[60]  Margit Burmeister,et al.  BDNF Val66Met Allele Is Associated with Reduced Hippocampal Volume in Healthy Subjects , 2006, Biological Psychiatry.

[61]  Pienie Zwitserlood,et al.  Reduced amygdala-prefrontal coupling in major depression: association with MAOA genotype and illness severity. , 2009, The international journal of neuropsychopharmacology.

[62]  S. Potkin,et al.  Genome-wide strategies for discovering genetic influences on cognition and cognitive disorders: Methodological considerations , 2009, Cognitive neuropsychiatry.

[63]  W. Drevets,et al.  Imaging phenotypes of major depressive disorder: genetic correlates , 2009, Neuroscience.

[64]  A M McIntosh,et al.  A GRIK4 variant conferring protection against bipolar disorder modulates hippocampal function , 2009, Molecular Psychiatry.

[65]  Kiyotaka Nemoto,et al.  Dose-dependent effect of the Val66Met polymorphism of the brain-derived neurotrophic factor gene on memory-related hippocampal activity , 2008, Neuroscience Research.

[66]  Eric Stice,et al.  Frontal-Limbic White Matter Pathway Associations with the Serotonin Transporter Gene Promoter Region (5-HTTLPR) Polymorphism , 2009, The Journal of Neuroscience.

[67]  Michael F Egan,et al.  A susceptibility gene for affective disorders and the response of the human amygdala. , 2005, Archives of general psychiatry.

[68]  A. Meyer-Lindenberg,et al.  Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression , 2008, Molecular Psychiatry.

[69]  R Todd Constable,et al.  Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[70]  Ole A. Andreassen,et al.  Evidence for a possible association of neurotrophin receptor (NTRK-3) gene polymorphisms with hippocampal function and schizophrenia , 2009, Neurobiology of Disease.

[71]  J. Ferri,et al.  Genetics of emotion regulation , 2009, Neuroscience.

[72]  Bruce S. McEwen,et al.  Neurobiological and Clinical Effects of the Antidepressant Tianeptine , 2008, CNS drugs.

[73]  Brent A. Vogt,et al.  Cingulate Neurobiology and Disease , 2009 .

[74]  M. Alda,et al.  Reduced subgenual cingulate volumes in mood disorders: a meta-analysis. , 2008, Journal of psychiatry & neuroscience : JPN.

[75]  David Goldman,et al.  Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. , 2006, American journal of human genetics.

[76]  Ariel Graff-Guerrero,et al.  Frontal and limbic metabolic differences in subjects selected according to genetic variation of the SLC6A4 gene polymorphism , 2005, NeuroImage.

[77]  Peter Zwanzger,et al.  Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. , 2004, Archives of general psychiatry.

[78]  Tadafumi Kato,et al.  Molecular genetics of bipolar disorder and depression , 2007, Psychiatry and clinical neurosciences.

[79]  M C O'Donovan,et al.  The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons , 2006, Molecular Psychiatry.

[80]  Daniel R Weinberger,et al.  Imaging genomics. , 2003, British medical bulletin.

[81]  M. Furey,et al.  Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression , 2008, Brain Structure and Function.

[82]  S. Rauch,et al.  Neurobiology of emotion perception I: the neural basis of normal emotion perception , 2003, Biological Psychiatry.

[83]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[84]  J. Price,et al.  Neurocircuitry of Mood Disorders , 2010, Neuropsychopharmacology.

[85]  Katharina Domschke,et al.  Imaging genetics of anxiety disorders , 2010, NeuroImage.

[86]  M. Burmeister,et al.  Meta‐analysis of the association between a serotonin transporter promoter polymorphism (5‐HTTLPR) and anxiety‐related personality traits , 2004, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[87]  Gloria Olivieri,et al.  ‘Negativity bias’ in risk for depression and anxiety: Brain–body fear circuitry correlates, 5-HTT-LPR and early life stress , 2009, NeuroImage.

[88]  Jonathan Flint,et al.  Is there an association between NPY and neuroticism? , 2009, Nature.

[89]  Thomas Frodl,et al.  Reduced hippocampal volumes associated with the long variant of the tri‐ and diallelic serotonin transporter polymorphism in major depression , 2008, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[90]  D. Skuse,et al.  Functional dissociation of amygdala-modulated arousal and cognitive appraisal, in Turner syndrome. , 2005, Brain : a journal of neurology.

[91]  Joseph H. Callicott,et al.  Impact of interacting functional variants in COMT on regional gray matter volume in human brain , 2009, NeuroImage.

[92]  Takashi Asada,et al.  The Val66Met polymorphism of the brain-derived neurotrophic factor gene affects age-related brain morphology , 2006, Neuroscience Letters.

[93]  Ryan Bogdan,et al.  Variation in TREK1 gene linked to depression‐resistant phenotype is associated with potentiated neural responses to rewards in humans , 2009, Human brain mapping.

[94]  Richard Coppola,et al.  The G72/G30 Gene Complex and Cognitive Abnormalities in Schizophrenia , 2006, Neuropsychopharmacology.

[95]  Warren D Taylor,et al.  Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. , 2005, Archives of general psychiatry.

[96]  S. Rauch,et al.  Neurobiology of emotion perception II: implications for major psychiatric disorders , 2003, Biological Psychiatry.

[97]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[98]  Francesco Fera,et al.  Genetically dependent modulation of serotonergic inactivation in the human prefrontal cortex , 2008, NeuroImage.

[99]  E. Castrén,et al.  Is mood chemistry? , 2005, Nature Reviews Neuroscience.

[100]  Nikos Makris,et al.  Association of a polymorphism near CREB1 with differential aversion processing in the insula of healthy participants. , 2008, Archives of general psychiatry.

[101]  G. Rosoklija,et al.  Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression , 2008, Molecular Psychiatry.

[102]  A M McIntosh,et al.  Modulation of hippocampal activation by genetic variation in the GRIK4 gene , 2009, Molecular Psychiatry.

[103]  Sophia Frangou,et al.  The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study. , 2009, The international journal of neuropsychopharmacology.

[104]  Fabio Sambataro,et al.  Association of the Ser704Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding , 2008, The European journal of neuroscience.

[105]  Nadim Joni Shah,et al.  A putative high risk diplotype of the G72 gene is in healthy individuals associated with better performance in working memory functions and altered brain activity in the medial temporal lobe , 2009, NeuroImage.

[106]  B. Ham,et al.  Serotonergic genes and amygdala activity in response to negative affective facial stimuli in Korean women , 2008, Genes, brain, and behavior.

[107]  J. P. Hamilton,et al.  Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies , 2008, Molecular Psychiatry.

[108]  Edmund T Rolls,et al.  An attractor network in the hippocampus: theory and neurophysiology. , 2007, Learning & memory.

[109]  A. Grace,et al.  The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes , 2004, Neuropsychopharmacology.

[110]  J. Price,et al.  Glial reduction in the subgenual prefrontal cortex in mood disorders. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[111]  E. Rolls,et al.  A computational theory of hippocampal function, and empirical tests of the theory , 2006, Progress in Neurobiology.

[112]  M. Egan,et al.  Brain-Derived Neurotrophic Factor val66met Polymorphism Affects Human Memory-Related Hippocampal Activity and Predicts Memory Performance , 2003, The Journal of Neuroscience.

[113]  Allan L. Reiss,et al.  Amygdala and hippocampal volumes in Turner syndrome: a high-resolution MRI study of X-monosomy , 2004, Neuropsychologia.

[114]  Karl J. Friston,et al.  Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex, and fear recognition in humans. , 2003, Brain : a journal of neurology.

[115]  Walter Heindel,et al.  Cannabinoid receptor 1 (CNR1) gene: Impact on antidepressant treatment response and emotion processing in Major Depression , 2008, European Neuropsychopharmacology.

[116]  S. Tsai,et al.  Association Study of a Monoamine Oxidase A Gene Promoter Polymorphism with Major Depressive Disorder and Antidepressant Response , 2005, Neuropsychopharmacology.

[117]  C. Montag,et al.  The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression , 2009, Psychological Medicine.

[118]  Ahmad R. Hariri,et al.  Serotonin Transporter Genotype (5-HTTLPR): Effects of Neutral and Undefined Conditions on Amygdala Activation , 2007, Biological Psychiatry.

[119]  R Todd Constable,et al.  Role of Variation in the Serotonin Transporter Protein Gene (SLC6A4) in Trait Disturbances in the Ventral Anterior Cingulate in Bipolar Disorder , 2009, Neuropsychopharmacology.

[120]  Matthew S. Grubb,et al.  Adult neurogenesis and functional plasticity in neuronal circuits , 2006, Nature Reviews Neuroscience.

[121]  John A. Detre,et al.  Genetic Variation in Serotonin Transporter Alters Resting Brain Function in Healthy Individuals , 2007, Biological Psychiatry.

[122]  Dinggang Shen,et al.  Automated morphometric study of brain variation in XXY males , 2004, NeuroImage.

[123]  P. Whalen,et al.  The Structural Integrity of an Amygdala–Prefrontal Pathway Predicts Trait Anxiety , 2009, The Journal of Neuroscience.

[124]  Thomas E. Nichols,et al.  Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder. , 2009, Archives of general psychiatry.

[125]  Timothy Edward John Behrens,et al.  Contrasting roles for cingulate and orbitofrontal cortex in decisions and social behaviour , 2007, Trends in Cognitive Sciences.

[126]  R. Kahn,et al.  Effects of brain‐derived neurotrophic factor Val66Met polymorphism on hippocampal volume change in schizophrenia , 2010, Hippocampus.

[127]  Andreas Heinz,et al.  A model comparison of COMT effects on central processing of affective stimuli , 2009, NeuroImage.

[128]  Takahisa Taguchi,et al.  Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. , 2006, Human molecular genetics.

[129]  B. Kolachana,et al.  Variation in dopamine genes influences responsivity of the human reward system , 2009, Proceedings of the National Academy of Sciences.

[130]  J. Groves,et al.  Is it time to reassess the BDNF hypothesis of depression? , 2007, Molecular Psychiatry.

[131]  M. Raichle,et al.  Subgenual prefrontal cortex abnormalities in mood disorders , 1997, Nature.

[132]  B. Kolachana,et al.  Epistasis between Dopamine Regulating Genes Identifies a Nonlinear Response of the Human Hippocampus During Memory Tasks , 2008, Biological Psychiatry.

[133]  W. Drevets,et al.  The Subgenual Anterior Cingulate Cortex in Mood Disorders , 2008, CNS Spectrums.

[134]  Daniel Mathalon,et al.  A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. , 2009, Schizophrenia bulletin.

[135]  P. Vallet,et al.  Excess of serotonin affects embryonic interneuron migration through activation of the serotonin receptor 6 , 2009, Molecular Psychiatry.

[136]  Peter R Schofield,et al.  Serotonin transporter gene status predicts caudate nucleus but not amygdala or hippocampal volumes in older persons with major depression. , 2007, Journal of affective disorders.

[137]  Antonio Cerasa,et al.  Impact of catechol-O-methyltransferase Val108/158 Met genotype on hippocampal and prefrontal gray matter volume , 2008, Neuroreport.

[138]  J. John Mann,et al.  Effect of BDNF val66met polymorphism on age-related amygdala volume changes in healthy subjects , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[139]  Andreas Meyer-Lindenberg,et al.  Neural connectivity as an intermediate phenotype: Brain networks under genetic control , 2009, Human brain mapping.

[140]  B. McEwen,et al.  Plasticity of the Hippocampus: Adaptation to Chronic Stress and Allostatic Load , 2001, Annals of the New York Academy of Sciences.

[141]  A. Hariri,et al.  A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity , 2005, Molecular Psychiatry.

[142]  Christian Büchel,et al.  Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter , 2005, Nature Neuroscience.

[143]  A. Meyer-Lindenberg,et al.  The Brain-derived Neurotrophic Factor Val66met Polymorphism and Variation in Human Cortical Morphology , 2022 .

[144]  Christian Büchel,et al.  5-HTT genotype effect on prefrontal–amygdala coupling differs between major depression and controls , 2009, Psychopharmacology.

[145]  S. Cichon,et al.  G72 and its association with major depression and neuroticism in large population-based groups from Germany. , 2008, The American journal of psychiatry.

[146]  Ahmad R. Hariri,et al.  Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission , 2009, Molecular Psychiatry.

[147]  John P Hatch,et al.  Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder , 2009, Neuropsychopharmacology.

[148]  A. Hariri,et al.  Neuroimaging studies of serotonin gene polymorphisms: Exploring the interplay of genes, brain, and behavior , 2006, Cognitive, affective & behavioral neuroscience.

[149]  Paul J. Harrison,et al.  Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders , 2008, Neuropsychopharmacology.

[150]  S. Potkin,et al.  Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia , 2009, Molecular Psychiatry.

[151]  D Robinson,et al.  Brain-derived neurotrophic factor Val66met polymorphism and volume of the hippocampal formation , 2005, Molecular Psychiatry.

[152]  A. Schleicher,et al.  Receptor architecture of human cingulate cortex: Evaluation of the four‐region neurobiological model , 2009, Human brain mapping.

[153]  D. Hamer,et al.  A functional polymorphism in the monoamine oxidase A gene promoter , 1998, Human Genetics.

[154]  Andrew J. Saykin,et al.  Voxelwise genome-wide association study (vGWAS) , 2010, NeuroImage.

[155]  Hidehiro Iida,et al.  The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia. , 2006, Brain : a journal of neurology.

[156]  Matcheri S. Keshavan,et al.  Disruption of Orbitofrontal Cortex Laterality in Offspring from Multiplex Alcohol Dependence Families , 2009, Biological Psychiatry.

[157]  M. Reuter,et al.  Dopamine DRD2 polymorphism alters reversal learning and associated neural activity , 2009, NeuroImage.

[158]  Marcus R. Munafò,et al.  Serotonin Transporter (5-HTTLPR) Genotype and Amygdala Activation: A Meta-Analysis , 2008, Biological Psychiatry.

[159]  P. Muglia,et al.  Association of DISC1 and TSNAX genes and affective disorders in the depression case–control (DeCC) and bipolar affective case–control (BACCS) studies , 2010, Molecular Psychiatry.

[160]  Leanne M Williams,et al.  COMT Val108/158Met polymorphism effects on emotional brain function and negativity bias , 2010, NeuroImage.

[161]  Ahmad R. Hariri,et al.  Divergent Effects of Genetic Variation in Endocannabinoid Signaling on Human Threat- and Reward-Related Brain Function , 2009, Biological Psychiatry.

[162]  Michael X. Cohen,et al.  Individual differences in extraversion and dopamine genetics predict neural reward responses. , 2005, Brain research. Cognitive brain research.

[163]  Jürgen Gallinat,et al.  Association of a functional BDNF polymorphism and anxiety-related personality traits , 2005, Psychopharmacology.

[164]  E. Rolls,et al.  The orbitofrontal cortex and beyond: From affect to decision-making , 2008, Progress in Neurobiology.

[165]  Tilo Kircher,et al.  COMT genotype and its role on hippocampal–prefrontal regions in declarative memory , 2010, NeuroImage.

[166]  Aaron D. Boes,et al.  Rostral Anterior Cingulate Cortex Volume Correlates with Depressed Mood in Normal Healthy Children , 2008, Biological Psychiatry.

[167]  James R. MacFall,et al.  The COMT Val158Met polymorphism and temporal lobe morphometry in healthy adults , 2007, Psychiatry Research: Neuroimaging.

[168]  I. Sora,et al.  Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders , 2003, Genes, brain, and behavior.

[169]  T G Schulze,et al.  Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. , 2000, American journal of medical genetics.

[170]  R A Bryant,et al.  Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety , 2009, Molecular Psychiatry.

[171]  P. Buckley,et al.  Catechol O-methyltransferase Val158Met Genotype and Neural Mechanisms Related to Affective Arousal and Regulation , 2008 .

[172]  K. Lesch,et al.  Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region , 1996, Science.

[173]  Danielle S. Bassett,et al.  A validated network of effective amygdala connectivity , 2007, NeuroImage.

[174]  Danielle L. Graham,et al.  Essential Role of BDNF in the Mesolimbic Dopamine Pathway in Social Defeat Stress , 2006, Science.

[175]  Andreas Heinz,et al.  Catechol-O-Methyltransferase val158met Genotype Affects Processing of Emotional Stimuli in the Amygdala and Prefrontal Cortex , 2005, The Journal of Neuroscience.

[176]  Norihiro Sadato,et al.  A Variant C178T in the Regulatory Region of the Serotonin Receptor Gene HTR3A Modulates Neural Activation in the Human Amygdala , 2005, The Journal of Neuroscience.

[177]  Randy L. Gollub,et al.  The COMT Val108/158Met polymorphism and medial temporal lobe volumetry in patients with schizophrenia and healthy adults , 2009, NeuroImage.

[178]  Marina Boccardi,et al.  Influence of serotonin receptor 2A His452Tyr polymorphism on brain temporal structures: a volumetric MR study , 2006, European Journal of Human Genetics.

[179]  Hans-Jürgen Möller,et al.  Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. , 2007, Archives of general psychiatry.

[180]  Patrick M Fisher,et al.  Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. , 2009, Archives of general psychiatry.

[181]  F. Holsboer,et al.  Stress and the brain: from adaptation to disease , 2005, Nature Reviews Neuroscience.

[182]  M. Munafo,et al.  Forum: interactions between gene and environment , 2008, Current opinion in psychiatry.

[183]  A. Meyer-Lindenberg,et al.  Intermediate phenotypes and genetic mechanisms of psychiatric disorders , 2006, Nature Reviews Neuroscience.

[184]  G. Vandewalle,et al.  Functional Magnetic Resonance Imaging-Assessed Brain Responses during an Executive Task Depend on Interaction of Sleep Homeostasis, Circadian Phase, and PER3 Genotype , 2009, The Journal of Neuroscience.

[185]  James McKirdy,et al.  Genetic variation in the G72 (DAOA) gene affects temporal lobe and amygdala structure in subjects affected by bipolar disorder. , 2009, Bipolar disorders.

[186]  K. Shokat,et al.  Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure , 2006, Science.

[187]  Daniel R. Weinberger,et al.  Variation of Human Amygdala Response During Threatening Stimuli as a Function of 5′HTTLPR Genotype and Personality Style , 2005, Biological Psychiatry.

[188]  Walter Heindel,et al.  5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression , 2008, Neuropsychopharmacology.

[189]  H. Breiter,et al.  BDNF, relative preference, and reward circuitry responses to emotional communication , 2009, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[190]  Carol Dobson-Stone,et al.  Disturbances in selective information processing associated with the BDNF Val66Met polymorphism: Evidence from cognition, the P300 and fronto-hippocampal systems , 2009, Biological Psychology.

[191]  Gustavo Turecki,et al.  Impaired Repression at a 5-Hydroxytryptamine 1A Receptor Gene Polymorphism Associated with Major Depression and Suicide , 2003, The Journal of Neuroscience.

[192]  A. Kersting,et al.  Serotonergic genes modulate amygdala activity in major depression , 2007, Genes, brain, and behavior.

[193]  Walter Heindel,et al.  Emotion specific modulation of automatic amygdala responses by 5-HTTLPR genotype , 2010, NeuroImage.

[194]  Eliza Congdon,et al.  Neural correlates of epigenesis , 2006, Proceedings of the National Academy of Sciences.

[195]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[196]  Matthäus Willeit,et al.  Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry , 2010, NeuroImage.

[197]  Ahmad R. Hariri,et al.  Genetic Variation in Maoa Modulates Ventromedial Prefrontal Circuitry Mediating Individual Differences in Human Personality , 2022 .

[198]  P. Gaspar,et al.  The developmental role of serotonin: news from mouse molecular genetics , 2003, Nature Reviews Neuroscience.

[199]  A. Falini,et al.  Clock genes beyond the clock: CLOCK genotype biases neural correlates of moral valence decision in depressed patients , 2007, Genes, brain, and behavior.

[200]  Joel Gelernter,et al.  Influence of Vascular Endothelial Growth Factor Variation on Human Hippocampus Morphology , 2008, Biological Psychiatry.

[201]  E. Pomarol-Clotet,et al.  COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects , 2010, NeuroImage.

[202]  A. Meyer-Lindenberg,et al.  Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans , 2009, Molecular Psychiatry.

[203]  Margot Albus,et al.  Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression , 2004, Biological Psychiatry.

[204]  A. Meyer-Lindenberg,et al.  5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression , 2005, Nature Neuroscience.

[205]  Hans-Jürgen Möller,et al.  Anger- and aggression-related traits are associated with polymorphisms in the 5-HT-2A gene. , 2006, Journal of affective disorders.