Advertisement

Depression, Neuroimaging and Connectomics: A Selective Overview

  • Qiyong Gong
    Affiliations
    Huaxi Magnetic Resonance Research Center, Department of Radiology, Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, China

    Department of Psychiatry , Yale University School of Medicine, New Haven, Connecticut

    Department of Psychiatry, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu
    Search for articles by this author
  • Yong He
    Correspondence
    Address correspondence to Yong He, Ph.D., Beijing Normal University, State Key Laboratory of Cognitive Neuroscience and Learning, Brain Imaging Center Rm303, No 19 Xinjiekouwai Street, Beijing, Beijing 100875, China.
    Affiliations
    State Key Laboratory of Cognitive Neuroscience and Learning and International Digital Group/McGovern Institute for Brain Research

    Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
    Search for articles by this author

      Abstract

      Depression is a multifactorial disorder with clinically heterogeneous features involving disturbances of mood and cognitive function. Noninvasive neuroimaging studies have provided rich evidence that these behavioral deficits in depression are associated with structural and functional abnormalities in specific regions and connections. Recent advances in brain connectomics through the use of graph theory highlight disrupted topological organization of large-scale functional and structural brain networks in depression, involving global topology (e.g., local clustering, shortest-path lengths, and global and local efficiencies), modular structure, and network hubs. These system-level disruptions show important correlates with genetic and environmental factors, which provide an integrative perspective on mood and cognitive deficits in depressive syndrome. Moreover, research suggests that the pathologic networks associated with depression represent potentially valuable biomarkers for early detection of this disorder and they are likely to be regulated and recalibrated by using pharmacologic, psychological, and brain stimulation therapies. These connectome-based imaging studies present new opportunities to reconceptualize the pathogenesis of depression, improve our knowledge of the biological mechanisms of therapeutic effects, and identify appropriate stimulation targets to optimize the clinical response in depression treatment. Here, we summarize the current findings and historical understanding of structural and functional connectomes in depression, focusing on graph analyses of depressive brain networks. We also consider methodological factors such as sample heterogeneity and poor test-retest reliability of recordings due to physiological, head motion, and imaging artifacts to discuss result inconsistencies among studies. We conclude with suggestions for future research directions on the emerging field of imaging connectomics in depression.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gotlib I.
        • Joormann J.
        Cognition and depression: Current status and future directions.
        Annu Rev Clin Psychol. 2010; 6: 285-312
        • Mayberg H.
        Limbic-cortical dysregulation: A proposed model of depression.
        J Neuropsychiatry Clin Neurosci. 1997; 9: 471-481
        • Drevets W.
        • Price J.
        • Furey M.
        Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression.
        Brain Struct Funct. 2008; 213: 93-118
        • Hamilton J.
        • Chen M.
        • Gotlib I.
        Neural systems approaches to understanding major depressive disorder: An intrinsic functional organization perspective.
        Neurobiol Dis. 2013; 52: 4-11
        • Lui S.
        • Parkes L.
        • Huang X.
        • Zou K.
        • Chan R.
        • Yang H.
        • et al.
        Depressive disorders: Focally altered cerebral perfusion measured with arterial spin-labeling MR imaging.
        Radiology. 2009; 251: 476-484
        • Sheline Y.
        Depression and the hippocampus: Cause or effect?.
        Biol Psychiatry. 2011; 70: 308-309
        • Fitzgerald P.
        • Oxley T.
        • Laird A.
        • Kulkarni J.
        • Egan G.
        • Daskalakis Z.
        An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression.
        Psychiatry Res. 2006; 148: 33-45
        • Pizzagalli D.
        Frontocingulate dysfunction in depression: Toward biomarkers of treatment response.
        Neuropsychopharmacology. 2011; 36: 183-206
        • Mah L.
        • Zarate Jr, C.A.
        • Singh J.
        • Duan Y.
        • Luckenbaugh D.
        • Manji H.
        • Drevets W.C.
        Regional cerebral glucose metabolic abnormalities in bipolar II depression.
        Biol Psychiatry. 2007; 61: 765-775
        • Drevets W.
        • Bogers W.
        • Raichle M.
        Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism.
        Eur Neuropsychopharmacol. 2002; 12: 527-544
        • Kim M.
        • Hamilton J.
        • Gotlib I.
        Reduced caudate gray matter volume in women with major depressive disorder.
        Psychiatry Res. 2008; 164: 114-122
        • Krishnan K.
        • McDonald W.
        • Escalona P.
        • Doraiswamy P.
        • Na C.
        • Husain M.
        • et al.
        Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations.
        Arch Gen Psychiatry. 1992; 49: 553-557
        • Pizzagalli D.
        • Holmes A.
        • Dillon D.
        • Goetz E.
        • Birk J.
        • Bogdan R.
        • et al.
        Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder.
        Am J Psychiatry. 2009; 166: 702-710
        • Zhu X.
        • Wang X.
        • Xiao J.
        • Liao J.
        • Zhong M.
        • Wang W.
        • Yao S.
        Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients.
        Biol Psychiatry. 2012; 71: 611-617
        • Wu D.
        • Yuan Y.
        • Bai F.
        • You J.
        • Li L.
        • Zhang Z.
        Abnormal functional connectivity of the default mode network in remitted late-onset depression.
        J Affect Disord. 2012; 147: 277-287
        • Wang Z.
        • Yuan Y.
        • Bai F.
        • You J.
        • Li L.
        • Zhang Z.
        Abnormal default-mode network in angiotensin converting enzyme D allele carriers with remitted geriatric depression.
        Behav Brain Res. 2012; 230: 325-332
        • Frodl T.
        • Bokde A.L.
        • Scheuerecker J.
        • Lisiecka D.
        • Schoepf V.
        • Hampel H.
        • et al.
        Functional connectivity bias of the orbitofrontal cortex in drug-free patients with major depression.
        Biol Psychiatry. 2010; 67: 161-167
        • Sheline Y.
        • Price J.
        • Yan Z.
        • Mintun M.
        Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus.
        Proc Natl Acad Sci U S A. 2010; 107: 11020-11025
        • Greicius M.
        • Flores B.
        • Menon V.
        • Glover G.
        • Solvason H.
        • Kenna H.
        • et al.
        Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus.
        Biol Psychiatry. 2007; 62: 429-437
        • Connolly C.
        • Wu J.
        • Ho T.
        • Hoeft F.
        • Wolkowitz O.
        • Eisendrath S.
        • et al.
        Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents.
        Biol Psychiatry. 2013; 74: 898-907
        • Anand A.
        • Li Y.
        • Wang Y.
        • Lowe M.
        • Dzemidzic M.
        Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression.
        Psychiatry Res. 2009; 171: 189-198
        • Lui S.
        • Wu Q.
        • Qiu L.
        • Yang X.
        • Kuang W.
        • Chan R.
        • et al.
        Resting-state functional connectivity in treatment-resistant depression.
        Am J Psychiatry. 2011; 168: 642-648
        • Qiu L.
        • Lui S.
        • Kuang W.
        • Huang X.
        • Li J.
        • Li J.
        • et al.
        Regional increases of cortical thickness in untreated, first-episode major depressive disorder.
        Transl Psychiatry. 2014; 4: e378
        • Liao Y.
        • Huang X.
        • Wu Q.
        • Yang C.
        • Kuang W.
        • Du M.
        • et al.
        Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD.
        J Psychiatry Neurosci. 2013; 38: 49-56
        • Bae J.
        • MacFall J.
        • Krishnan K.
        • Payne M.
        • Steffens D.
        • Taylor W.
        Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression.
        Biol Psychiatry. 2006; 60: 1356-1363
        • Sporns O.
        • Tononi G.
        • Kotter R.
        The human connectome: A structural description of the human brain.
        PLoS Comput Biol. 2005; 1: e42
        • Bullmore E.
        • Sporns O.
        The economy of brain network organization.
        Nat Rev Neurosci. 2012; 13: 336-349
        • Bullmore E.
        • Sporns O.
        Complex brain networks: Graph theoretical analysis of structural and functional systems.
        Nat Rev Neurosci. 2009; 10: 186-198
        • He Y.
        • Evans
        A graph theoretical modeling of brain connectivity.
        Curr Opin Neurol. 2010; 23: 341-350
        • van den Heuvel M.
        • Sporns O.
        Network hubs in the human brain.
        Trends Cogn Sci. 2013; 17: 683-696
        • Filippi M.
        • van den Heuvel M.
        • Fornito A.
        • He Y.
        • Hulshoff Pol H.
        • Agosta F.
        • et al.
        Assessment of system dysfunction in the brain through MRI-based connectomics.
        Lancet Neurol. 2013; 12: 1189-1199
        • Sporns O.
        Network attributes for segregation and integration in the human brain.
        Curr Opin Neurobiol. 2013; 23: 162-171
        • Fornito A.
        • Zalesky A.
        • Pantelis C.
        • Bullmore E.
        Schizophrenia, neuroimaging and connectomics.
        Neuroimage. 2012; 62: 2296-2314
        • van den Heuvel M.
        • Sporns O.
        • Collin G.
        • Scheewe T.
        • Mandl R.
        • Cahn W.
        • et al.
        Abnormal rich club organization and functional brain dynamics in schizophrenia.
        JAMA Psychiatry. 2013; 70: 783-792
        • Lo C.
        • Wang P.
        • Chou K.
        • Wang J.
        • He Y.
        • Lin C.
        Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer׳s disease.
        J Neurosci. 2010; 30: 16876-16885
        • Wang J.
        • Zuo X.
        • Dai Z.
        • Xia M.
        • Zhao Z.
        • Zhao X.
        • et al.
        Disrupted functional brain connectome in individuals at risk for Alzheimer׳s disease.
        Biol Psychiatry. 2013; 73: 472-481
        • Dai Z.
        • He Y.
        Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer׳s disease.
        Neurosci Bull. 2014; 30: 217-232
        • Zhang J.
        • Wang J.
        • Wu Q.
        • Kuang W.
        • Huang X.
        • He Y.
        • Gong Q.
        Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder.
        Biol Psychiatry. 2011; 70: 334-342
        • Meng C.
        • Brandl F.
        • Tahmasian M.
        • Shao J.
        • Manoliu A.
        • Scherr M.
        • et al.
        Aberrant topology of striatum׳s connectivity is associated with the number of episodes in depression.
        Brain. 2014; 137: 598-609
        • Lord A.
        • Horn D.
        • Breakspear M.
        • Walter M.
        Changes in community structure of resting state functional connectivity in unipolar depression.
        PLoS One. 2012; 7: e41282
        • Bohr I.
        • Kenny E.
        • Blamire A.
        • O׳Brien J.
        • Thomas A.
        • Richardson J.
        • Kaiser M.
        Resting-state functional connectivity in late-life depression: Higher global connectivity and more long distance connections.
        Front Psychiatry. 2013; 3: 116
        • Tao H.
        • Guo S.
        • Ge T.
        • Kendrick K.
        • Xue Z.
        • Liu Z.
        • Feng J.
        Depression uncouples brain hate circuit.
        Mol Psychiatry. 2013; 18: 101-111
        • Jin C.
        • Gao C.
        • Chen C.
        • Ma S.
        • Netra R.
        • Wang Y.
        • et al.
        A preliminary study of the dysregulation of the resting networks in first-episode medication-naive adolescent depression.
        Neurosci Lett. 2011; 503: 105-109
        • Singh M.
        • Kesler S.
        • Hadi Hosseini S.
        • Kelley R.
        • Amatya D.
        • Hamilton J.
        • et al.
        Anomalous gray matter structural networks in major depressive disorder.
        Biol Psychiatry. 2013; 74: 777-785
        • Ajilore O.
        • Lamar M.
        • Leow A.
        • Zhang A.
        • Yang S.
        • Kumar A.
        Graph theory analysis of cortical-subcortical networks in late-life depression.
        Am J Geriatr Psychiatry. 2014; 22: 195-206
        • Bai F.
        • Shu N.
        • Yuan Y.
        • Shi Y.
        • Yu H.
        • Wu D.
        • et al.
        Topologically convergent and divergent structural connectivity patterns between patients with remitted geriatric depression and amnestic mild cognitive impairment.
        J Neurosci. 2012; 32: 4307-4318
        • Qin J.
        • Wei M.
        • Liu H.
        • Yan R.
        • Luo G.
        • Yao Z.
        • Lu Q.
        Abnormal brain anatomical topological organization of the cognitive-emotional and the frontoparietal circuitry in major depressive disorder [published online ahead of print November 22].
        Magn Reson Med. 2013; (doi:10.1002/mrm.25036)
        • Korgaonkar M.S.
        • Fornito A.
        • Williams L.M.
        • Grieve S.M.
        Abnormal structural networks characterize major depressive disorder: A connectome analysis.
        Biol Psychiatry. 2014; 76: 567-574
        • Wang L.
        • Dai Z.
        • Peng H.
        • Tan L.
        • Ding Y.
        • He Z.
        • et al.
        Overlapping and segregated resting-state functional connectivity in patients with major depressive disorder with and without childhood neglect.
        Hum Brain Mapp. 2014; 35: 1154-1166
        • Cisler J.
        • James G.
        • Tripathi S.
        • Mletzko T.
        • Heim C.
        • Hu X.
        • et al.
        Differential functional connectivity within an emotion regulation neural network among individuals resilient and susceptible to the depressogenic effects of early life stress.
        Psychol Med. 2013; 43: 507-518
        • Teicher M.
        • Anderson C.
        • Ohashi K.
        • Polcari A.
        Childhood maltreatment: Altered network centrality of cingulate, precuneus, temporal pole and insula.
        Biol Psychiatry. 2013; 76: 297-305
        • Craddock R.
        • Holtzheimer P.
        • Hu X.P.
        • Mayberg H.
        Disease state prediction from resting state functional connectivity.
        Magn Reson Med. 2009; 62: 1619-1628
        • Korgaonkar M.
        • Cooper N.
        • Williams L.
        • Grieve S.
        Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: A whole-brain diffusion tensor imaging tractography study.
        Neuroreport. 2012; 23: 566-571
        • Zeng L.
        • Shen H.
        • Liu L.
        • Wang L.
        • Li B.
        • Fang P.
        • et al.
        Identifying major depression using whole-brain functional connectivity: A multivariate pattern analysis.
        Brain. 2012; 135: 1498-1507
        • Guo H.
        • Cao X.
        • Liu Z.
        • Li H.
        • Chen J.
        • Zhang K.
        Machine learning classifier using abnormal brain network topological metrics in major depressive disorder.
        Neuroreport. 2012; 23: 1006-1011
        • Perrin J.
        • Merz S.
        • Bennett D.
        • Currie J.
        • Steele D.
        • Reid I.
        • Schwarzbauer C.
        Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder.
        Proc Natl Acad Sci U S A. 2012; 109: 5464-5468
        • Friston K.
        • Frith C.
        • Liddle P.
        • Frackowiak R.
        Functional connectivity: The principal-component analysis of large (PET) data sets.
        J Cereb Blood Flow Metab. 1993; 13: 5-14
        • Friston K.
        • Frith C.
        • Frackowiak R.
        Time-dependent changes in effective connectivity measured with PET.
        Hum Brain Mapp. 1993; 1: 69-80
        • Alexander-Bloch A.
        • Giedd J.
        • Bullmore E.
        Imaging structural co-variance between human brain regions.
        Nat Rev Neurosci. 2013; 14: 322-336
        • Boccaletti S.
        • Latora V.
        • Moreno Y.
        • Chavez M.
        • Hwang D.
        Complex networks: Structure and dynamics.
        Phys Reports. 2006; 424: 175-308
        • Watts D.J.
        • Strogatz S.H.
        Collective dynamics of ׳small-world׳ networks.
        Nature. 1998; 393: 440-442
        • Latora V.
        • Marchiori M.
        Efficient behavior of small-world networks.
        Phys Rev Lett. 2001; 87: 198701
        • He Y.
        • Chen Z.
        • Evans A.C.
        Small-world anatomical networks in the human brain revealed by cortical thickness from MRI.
        Cereb Cortex. 2007; 17: 2407-2419
        • Achard S.
        • Salvador R.
        • Whitcher B.
        • Suckling J.
        • Bullmore E.
        A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs.
        J Neurosci. 2006; 26: 63-72
        • Hagmann P.
        • Cammoun L.
        • Gigandet X.
        • Meuli R.
        • Honey C.
        • Wedeen V.
        • Sporns O.
        Mapping the structural core of human cerebral cortex.
        PLoS Biol. 2008; 6: e159
        • He Y.
        • Wang J.
        • Wang L.
        • Chen Z.J.
        • Yan C.
        • Yang H.
        • et al.
        Uncovering intrinsic modular organization of spontaneous brain activity in humans.
        PLoS One. 2009; 4: e5226
        • Meunier D.
        • Lambiotte R.
        • Fornito A.
        • Ersche K.
        • Bullmore E.
        Hierarchical modularity in human brain functional networks.
        Front Neuroinform. 2009; 3: 37
        • Gong G.
        • He Y.
        • Concha L.
        • Lebel C.
        • Gross D.
        • Evans A.
        • Beaulieu C.
        Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography.
        Cereb Cortex. 2009; 19: 524-536
        • Buckner R.
        • Sepulcre J.
        • Talukdar T.
        • Krienen F.M.
        • Liu H.
        • Hedden T.
        • et al.
        Cortical hubs revealed by intrinsic functional connectivity: Mapping, assessment of stability, and relation to Alzheimer’s disease.
        J Neurosci. 2009; 29: 1860-1873
        • Zuo X.
        • Ehmke R.
        • Mennes M.
        • Imperati D.
        • Castellanos F.
        • Sporns O.
        • Milham M.P.
        Network centrality in the human functional connectome.
        Cereb Cortex. 2012; 22: 1862-1875
        • Wang J.
        • Wang L.
        • Zang Y.
        • Yang H.
        • Tang H.
        • Gong Q.
        • et al.
        Parcellation-dependent small-world brain functional networks: A resting-state fMRI study.
        Hum Brain Mapp. 2009; 30: 1511-1523
        • Zalesky A.
        • Fornito A.
        • Harding I.
        • Cocchi L.
        • Yucel M.
        • Pantelis C.
        • Bullmore E.T.
        Whole-brain anatomical networks: Does the choice of nodes matter?.
        Neuroimage. 2010; 50: 970-983
        • Liang X.
        • Wang J.
        • Yan C.
        • Shu N.
        • Xu K.
        • Gong G.
        • He Y.
        Effects of different correlation metrics and preprocessing factors on small-world brain functional networks: A resting-state functional MRI study.
        PLoS One. 2012; 7: e32766
        • Steele J.
        • Lawrie S.
        Segregation of cognitive and emotional function in the prefrontal cortex: A stereotactic meta-analysis.
        Neuroimage. 2004; 21: 868-875
        • Young K.
        • Bellgowan P.
        • Bodurka J.
        • Drevets W.
        Behavioral and neurophysiological correlates of autobiographical memory deficits in patients with depression and individuals at high risk for depression.
        JAMA Psychiatry. 2013; 70: 698-708
        • Lehericy S.
        • Gerardin E.
        Normal functional imaging of the basal ganglia.
        Epileptic Disord. 2002; 4: S23-S30
        • Wu Q.
        • Li D.
        • Kuang W.
        • Zhang T.
        • Lui S.
        • Huang X.
        • et al.
        Abnormal regional spontaneous neural activity in treatment-refractory depression revealed by resting-state fMRI.
        Hum Brain Mapp. 2011; 32: 1290-1299
        • Gabbay V.
        • Hess D.A.
        • Liu S.
        • Babb J.
        • Klein R.
        • Gonen O.
        Lateralized caudate metabolic abnormalities in adolescent major depressive disorder: A proton MR spectroscopy study.
        Am J Psychiatry. 2007; 164: 1881-1889
        • Liang X.
        • Zou Q.
        • He Y.
        • Yang Y.
        Coupling of functional connectivity and regional cerebral blood flow reveals a physiological basis for network hubs of the human brain.
        Proc Natl Acad Sci U S A. 2013; 110: 1929-1934
        • Pine D.
        • Cohen E.
        • Cohen P.
        • Brook J.
        Adolescent depressive symptoms as predictors of adult depression: Moodiness or mood disorder?.
        Am J Psychiatry. 1999; 156: 133-135
        • Versace A.
        • Thompson W.
        • Zhou D.
        • Almeida J.
        • Hassel S.
        • Klein C.
        • et al.
        Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: State versus trait vulnerability markers of depression in bipolar disorder.
        Biol Psychiatry. 2010; 67: 422-431
        • Sexton C.
        • Allan C.
        • Le Masurier M.
        • McDermott L.
        • Kalu U.
        • Herrmann L.
        • et al.
        Magnetic resonance imaging in late-life depression: Multimodal examination of network disruption.
        Arch Gen Psychiatry. 2012; 69: 680-689
        • Alexopoulos G.
        • Hoptman M.
        • Kanellopoulos D.
        • Murphy C.
        • Lim K.
        • Gunning F.
        Functional connectivity in the cognitive control network and the default mode network in late-life depression.
        J Affect Disord. 2012; 139: 56-65
        • Zalesky A.
        • Fornito A.
        • Bullmore E.T.
        Network-based statistic: Identifying differences in brain networks.
        Neuroimage. 2010; 53: 1197-1207
        • Price J.
        • Drevets W.
        Neurocircuitry of mood disorders.
        Neuropsychopharmacology. 2010; 35: 192-216
        • Gong G.
        • He Y.
        • Chen Z.
        • Evans A.
        Convergence and divergence of thickness correlations with diffusion connections across the human cerebral cortex.
        Neuroimage. 2013; 59: 1239-1248
        • Alexander-Bloch A.
        • Raznahan A.
        • Bullmore E.
        • Giedd J.
        The convergence of maturational change and structural covariance in human cortical networks.
        J Neurosci. 2013; 33: 2889-2899
        • Hosseini S.
        • Kesler S.
        Comparing connectivity pattern and small-world organization between structural correlation and resting-state networks in healthy adults.
        Neuroimage. 2013; 78: 402-414
        • Sullivan P.
        • Neale M.
        • Kendler K.
        Genetic epidemiology of major depression: Review and meta-analysis.
        Am J Psychiatry. 2000; 157: 1552-1562
        • Lopez-Leon S.
        • Janssens A.
        • Gonzalez-Zuloeta Ladd A.
        • Del-Favero J.
        • Claes S.
        • Oostra B.
        • van Duijn C.M.
        Meta-analyses of genetic studies on major depressive disorder.
        Mol Psychiatry. 2008; 13: 772-785
        • Pezawas L.
        • Meyer-Lindenberg A.
        • Drabant E.
        • Verchinski B.
        • Munoz K.
        • Kolachana B.
        • et al.
        5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: A genetic susceptibility mechanism for depression.
        Nat Neurosci. 2005; 8: 828-834
        • Pezawas L.
        • Meyer-Lindenberg A.
        • Goldman A.
        • Verchinski B.
        • Chen G.
        • Kolachana B.
        • et al.
        Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression.
        Mol Psychiatry. 2008; 13: 709-716
        • Wiggins J.
        • Bedoyan J.
        • Peltier S.
        • Ashinoff S.
        • Carrasco M.
        • Weng S.
        • et al.
        The impact of serotonin transporter (5-HTTLPR) genotype on the development of resting-state functional connectivity in children and adolescents: A preliminary report.
        Neuroimage. 2012; 59: 2760-2770
        • van den Heuvel M.
        • van Soelen I.
        • Stam C.
        • Kahn R.
        • Boomsma D.
        • Hulshoff Pol H.
        Genetic control of functional brain network efficiency in children.
        Eur Neuropsychopharmacol. 2013; 23: 19-23
        • Fornito A.
        • Zalesky A.
        • Bassett D.
        • Meunier D.
        • Ellison-Wright I.
        • Yucel M.
        • et al.
        Genetic influences on cost-efficient organization of human cortical functional networks.
        J Neurosci. 2011; 31: 3261-3270
        • Brown J.
        • Terashima K.
        • Burggren A.
        • Ercoli L.
        • Miller K.
        • Small G.
        • Bookheimer S.Y.
        Brain network local interconnectivity loss in aging APOE-4 allele carriers.
        Proc Natl Acad Sci U S A. 2011; 108: 20760-20765
        • Heim C.
        • Nemeroff C.
        The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies.
        Biol Psychiatry. 2001; 49: 1023-1039
        • Widom C.
        • DuMont K.
        • Czaja S.
        A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up.
        Arch Gen Psychiatry. 2007; 64: 49-56
        • Agid O.
        • Kohn Y.
        • Lerer B.
        Environmental stress and psychiatric illness.
        Biomed Pharmacother. 2000; 54: 135-141
        • Heim C.
        • Plotsky P.
        • Nemeroff C.
        Importance of studying the contributions of early adverse experience to neurobiological findings in depression.
        Neuropsychopharmacology. 2004; 29: 641-648
        • Kaufman J.
        • Plotsky P.
        • Nemeroff C.
        • Charney D.
        Effects of early adverse experiences on brain structure and function: Clinical implications.
        Biol Psychiatry. 2000; 48: 778-790
        • Nanni V.
        • Uher R.
        • Danese
        A childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: A meta-analysis.
        Am J Psychiatry. 2012; 169: 141-151
        • Philip N.
        • Sweet L.
        • Tyrka A.
        • Price L.
        • Bloom R.
        • Carpenter L.
        Decreased default network connectivity is associated with early life stress in medication-free healthy adults.
        Eur Neuropsychopharmacol. 2013; 23: 24-32
        • Burghy C.
        • Stodola D.
        • Ruttle P.
        • Molloy E.
        • Armstrong J.
        • Oler J.
        • et al.
        Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence.
        Nat Neurosci. 2012; 15: 1736-1741
        • van der Werff S.
        • Pannekoek J.
        • Veer I.
        • van Tol M.
        • Aleman A.
        • Veltman D.
        • et al.
        Resting-state functional connectivity in adults with childhood emotional maltreatment.
        Psychol Med. 2013; 43: 1825-1836
        • van der Werff S.
        • Pannekoek J.
        • Veer I.
        • van Tol M.
        • Aleman A.
        • Veltman D.
        • et al.
        Resilience to childhood maltreatment is associated with increased resting-state functional connectivity of the salience network with the lingual gyrus.
        Child Abuse Negl. 2013; 37: 1021-1029
        • Paul R.
        • Henry L.
        • Grieve S.
        • Guilmette T.
        • Niaura R.
        • Bryant R.
        • et al.
        The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population.
        Neuropsychiatr Dis Treat. 2008; 4: 193-201
        • Coplan J.
        • Abdallah C.
        • Tang C.
        • Mathew S.
        • Martinez J.
        • Hof P.
        • et al.
        The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates.
        Neurosci Lett. 2010; 480: 93-96
        • Kendler K.
        • Kuhn J.
        • Vittum J.
        • Prescott C.
        • Riley B.
        The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: A replication.
        Arch Gen Psychiatry. 2005; 62: 529-535
        • Silberg J.
        • Pickles A.
        • Rutter M.
        • Hewitt J.
        • Simonoff E.
        • Maes H.
        • et al.
        The influence of genetic factors and life stress on depression among adolescent girls.
        Arch Gen Psychiatry. 1999; 56: 225-232
        • Uher R.
        • McGuffin P.
        The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: Review and methodological analysis.
        Mol Psychiatry. 2008; 13: 131-146
        • Caspi A.
        • Sugden K.
        • Moffitt T.
        • Taylor A.
        • Craig I.
        • Harrington H.
        • et al.
        Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene.
        Science. 2003; 301: 386-389
        • Alexander N.
        • Klucken T.
        • Koppe G.
        • Osinsky R.
        • Walter B.
        • Vaitl D.
        • et al.
        Interaction of the serotonin transporter-linked polymorphic region and environmental adversity: Increased amygdala-hypothalamus connectivity as a potential mechanism linking neural and endocrine hyperreactivity.
        Biol Psychiatry. 2012; 72: 49-56
        • Perez-Stable E.
        • Miranda J.
        • Munoz R.
        • Ying Y.
        Depression in medical outpatients. Underrecognition and misdiagnosis.
        Arch Intern Med. 1990; 150: 1083-1088
        • Mourao-Miranda J.
        • Bokde A.
        • Born C.
        • Hampel H.
        • Stetter M.
        Classifying brain states and determining the discriminating activation patterns: Support vector machine on functional MRI data.
        Neuroimage. 2005; 28: 980-995
        • Anderson R.
        • Frye M.
        • Abulseoud O.
        • Lee K.
        • McGillivray J.
        • Berk M.
        • Tye S.J.
        Deep brain stimulation for treatment-resistant depression: Efficacy, safety and mechanisms of action.
        Neurosci Biobehav Rev. 2012; 36: 1920-1933
        • Lozano A.
        • Lipsman N.
        Probing and regulating dysfunctional circuits using deep brain stimulation.
        Neuron. 2013; 77: 406-424
        • Mayberg H.S.
        Targeted electrode-based modulation of neural circuits for depression.
        J Clin Invest. 2009; 119: 717-725
        • Leuchter A.F.
        • Cook I.
        • Jin Y.
        • Phillips B.
        The relationship between brain oscillatory activity and therapeutic effectiveness of transcranial magnetic stimulation in the treatment of major depressive disorder.
        Front Hum Neurosci. 2013; 7: 37
        • Li B.
        • Liu L.
        • Friston K.
        • Shen H.
        • Wang L.
        • Zeng L.
        • Hu D.
        A treatment-resistant default mode subnetwork in major depression.
        Biol Psychiatry. 2013; 74: 48-54
        • McCabe C.
        • Mishor Z.
        Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers.
        Neuroimage. 2011; 57: 1317-1323
        • McCabe C.
        • Mishor Z.
        • Filippini N.
        • Cowen P.
        • Taylor M.
        • Harmer C.
        SSRI administration reduces resting state functional connectivity in dorso-medial prefrontal cortex.
        Mol Psychiatry. 2011; 16: 592-594
        • Scheidegger M.
        • Walter M.
        • Lehmann M.
        • Metzger C.
        • Grimm S.
        • Boeker H.
        • et al.
        Ketamine decreases resting state functional network connectivity in healthy subjects: Implications for antidepressant drug action.
        PLoS One. 2012; 7: e44799
        • Herbsman T.
        • Avery D.
        • Ramsey D.
        • Holtzheimer P.
        • Wadjik C.
        • Hardaway F.
        • et al.
        More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant response.
        Biol Psychiatry. 2009; 66: 509-515
        • Fox M.
        • Buckner R.
        • White M.
        • Greicius M.
        • Pascual-Leone A.
        Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate.
        Biol Psychiatry. 2012; 72: 595-603
        • Wang Z.
        • Dai Z.
        • Gong G.
        • Zhou C.
        • He Y.
        Understanding structural-functional relationships in the human brain: A large-scale network perspective.
        Neuroscientist. 2014; (doi:10.1177/1073858414537560)
        • Bi Y.
        • He Y.
        Connectomics reveals faulty wiring patterns for depressed brain.
        Biol Psychiatry. 2014; 76: 515-516
        • de Kwaasteniet B.
        • Ruhe E.
        • Caan M.
        • Rive M.
        • Olabarriaga S.
        • Groefsema M.
        • et al.
        Relation between structural and functional connectivity in major depressive disorder.
        Biol Psychiatry. 2013; 74: 40-47
        • Honey C.
        • Sporns O.
        • Cammoun L.
        • Gigandet X.
        • Thiran J.
        • Meuli R.
        • Hagmann P.
        Predicting human resting-state functional connectivity from structural connectivity.
        Proc Natl Acad Sci U S A. 2009; 106: 2035-2040
        • Tomasi D.
        • Wang G.
        • Volkow N.
        Energetic cost of brain functional connectivity.
        Proc Natl Acad Sci U S A. 2013; 110: 13642-13647
        • Musazzi L.
        • Treccani G.
        • Mallei A.
        • Popoli M.
        The action of antidepressants on the glutamate system: Regulation of glutamate release and glutamate receptors.
        Biol Psychiatry. 2013; 73: 1180-1188
        • Crossley N.
        • Mechelli A.
        • Scott J.
        • Carletti F.
        • Fox P.
        • McGuire P.
        • Bullmore E.T.
        The hubs of the human connectome are generally implicated in the anatomy of brain disorders.
        Brain. 2014; 137: 2382-2395
        • Liao X.
        • Xia M.
        • Xu T.
        • Dai Z.
        • Cao X.
        • Niu H.
        • et al.
        Functional brain hubs and their test-retest reliability: A multiband resting-state functional MRI study.
        Neuroimage. 2013; 83: 969-982
        • Wang J.
        • Zuo X.
        • Gohel S.
        • Milham M.
        • Biswal B.
        • He Y.
        Graph theoretical analysis of functional brain networks: Test-retest evaluation on short- and long-term resting-state functional MRI data.
        PLoS One. 2011; 6: e21976
        • Zuo X.
        • Xing X.
        Test-retest reliabilities of resting-state FMRI measurements in human brain functional connectomics: A systems neuroscience perspective.
        Neurosci Biobehav Rev. 2014; 45C: 100-118
        • Xia M.
        • Wang J.
        • He Y.
        BrainNet Viewer: A network visualization tool for human brain connectomics.
        PLoS One. 2013; 8: e68910