Brain Networks, Hormones and Genes Implicated in Depression

The Pre-frontal Limbic Network: Modulation of Synapses by Hormones and Epigenetic Mechanisms
  • Maxwell Bennett


The anterior cingulate cortex, amygdala and hippocampus form part of an interconnected prefrontal neocortical and limbic archicortical network, as shown in Fig. 5.1, which is dysregulated in major depressive disorders (MDD; for a review see Bennett 2010b). This dysregulation is manifest in decreased activity, according to functional magnetic imaging (fMRI) studies, in dorsal prefrontal areas such as dorsolateral prefrontal cortex (dlPFC), dorsomedial prefrontal cortex (dmPFC) and both dorsal and rostral anterior cingulate cortices (dACC and rACC) (Fig. 1; summarized in Table 1 of Taylor and Liberzon 2007). Such dysregulation is accompanied by increased activity in ventral prefrontal areas, namely in ventrolateral prefrontal cortex (vlPFC), in subgenual anterior cingulate cortex (sgACC) and in the amygdala (Fig. 1; Taylor and Liberzon 2007). These differences in activity during MDD have led to the concept that dorsal areas, associated with cognitive capacities, normally exert an inhibitory influence over more ventral areas, associated with affective capacities, but that this influence fails in those suffering from MDD (see Taylor and Liberzon 2007 for a critical review of this idea). Special emphasis is placed on the increased activity in the amygdala, as this has been correlated with a range of mood disorders (Bennett 2010b, 2011). This review canvases the mechanisms of interaction, relevant to MDD, between the PLN and three systems, namely those provided by the hypothalamic pituitary– adrenal axis, the basal ganglia and the midbrain.


Prefrontal Cortex Anterior Cingulate Cortex Ventral Tegmental Area Corticotropin Release Factor Suicide Victim 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M (1998) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 155:761–767PubMedGoogle Scholar
  2. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, van Heertum RL, Gorman JM, Laruelle M (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A 97:8104–8109PubMedCrossRefGoogle Scholar
  3. Ahearn EP, Jamison KR, Steffens DC, Cassidy F, Provenzale JM, Lehman A, Weisler RH, Carroll BJ, Krishnan KR (2001) MRI correlates of suicide attempt history in unipolar depression. Biol Psychiatry 50:266–270PubMedCrossRefGoogle Scholar
  4. Ahlenius S (1999) Clozapine: dopamine D1 receptor agonism in the prefrontal cortex as the code to decipher a Rosetta stone of antipsychotic drugs. Pharmacol Toxicol 84:193–196PubMedCrossRefGoogle Scholar
  5. Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113:296–320PubMedCrossRefGoogle Scholar
  6. Alexander GE, Crutcher MD (1990) Neural representations of the target (goal) of visually guided arm movements in three motor areas of the monkey. J Neurophysiol 64:164–178PubMedGoogle Scholar
  7. Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M (1997) ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 54:915–922PubMedCrossRefGoogle Scholar
  8. Alt SR, Turner JD, Klok MD, Meijer OC, Lakke EA, Derijk RH, Muller CP (2010) Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology 35:544–556PubMedCrossRefGoogle Scholar
  9. Autry AE, Adachi M, Cheng P, Monteggia LM (2009) Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior. Biol Psychiatry 66:84–90PubMedCrossRefGoogle Scholar
  10. Balleine BW, O’Doherty JP (2010) Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action. Neuropsychopharmacology 35:48–69PubMedCrossRefGoogle Scholar
  11. Balleine BW, Liljeholm M, Ostlund SB (2009) The integrative function of the basal ganglia in instrumental conditioning. Behav Brain Res 199:43–52PubMedCrossRefGoogle Scholar
  12. Ballmaier M, Toga AW, Blanton RE, Sowell ER, Lavretsky H, Peterson J, Pham D, Kumar A (2004) Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex. Am J Psychiatry 161:99–108PubMedCrossRefGoogle Scholar
  13. Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neurophar­macology 38:1083–1152PubMedCrossRefGoogle Scholar
  14. Bennett MR (2008a) Stress and anxiety in schizophrenia and depression: glucocorticoids, corticotropin-releasing hormone and synapse regression. Aust N Z J Psychiatry 42:995–1002CrossRefGoogle Scholar
  15. Bennett MR (2008b) Stress and anxiety in schizophrenia and depression: glucocorticoids, corticotropin-releasing hormone and synapse regression. Aust N Z J Psychiatry 42:995–1002CrossRefGoogle Scholar
  16. Bennett M (2009) Positive and negative symptoms in schizophrenia: the NMDA receptor hypofunction hypothesis, neuregulin/ErbB4 and synapse regression. Aust N Z J Psychiatry 43:711–721PubMedCrossRefGoogle Scholar
  17. Bennett MR (2010a) The prefrontal-limbic network in depression: modulation by hypothalamus, basal ganglia and midbrain. Prog Neurobiol 93:468–487CrossRefGoogle Scholar
  18. Bennett MR (2010b) Synapse regression in depression: the role of 5-HT receptors in modulating NMDA receptor function and synaptic plasticity. Aust N Z J Psychiatry 44:301–308PubMedCrossRefGoogle Scholar
  19. Bennett MR (2011) The prefrontal-limbic network in depression: a core pathology of synapse regression. Prog Neurobiol 93:457–467PubMedCrossRefGoogle Scholar
  20. Bensley LS, van Eenwyk J, Spieker SJ, Schoder J (1999) Self-reported abuse history and adolescent problem behaviors. I. Antisocial and suicidal behaviors. J Adolesc Health 24:163–172PubMedCrossRefGoogle Scholar
  21. Bonelli RM, Kapfhammer HP, Pillay SS, Yurgelun-Todd DA (2006) Basal ganglia volumetric studies in affective disorder: what did we learn in the last 15 years? J Neural Transm 113:255–268PubMedCrossRefGoogle Scholar
  22. Borsini F, Ceci A, Bietti G, Donetti A (1995) BIMT 17, a 5-HT1A receptor agonist/5-HT2A receptor antagonist, directly activates postsynaptic 5-HT inhibitory responses in the rat cerebral cortex. Naunyn Schmiedebergs Arch Pharmacol 352:283–290PubMedGoogle Scholar
  23. Bortolozzi A, Amargos-Bosch M, Adell A, Diaz-Mataix L, Serrats J, Pons S, Artigas F (2003) In vivo modulation of 5-hydroxytryptamine release in mouse prefrontal cortex by local 5-HT(2A) receptors: effect of antipsychotic drugs. Eur J Neurosci 18:1235–1246PubMedCrossRefGoogle Scholar
  24. Bortolozzi A, Diaz-Mataix L, Scorza MC, Celada P, Artigas F (2005) The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity. J Neurochem 95:1597–1607PubMedCrossRefGoogle Scholar
  25. Boyle MP, Brewer JA, Funatsu M, Wozniak DF, Tsien JZ, Izumi Y, Muglia LJ (2005) Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proc Natl Acad Sci U S A 102:473–478PubMedCrossRefGoogle Scholar
  26. Boyle MP, Kolber BJ, Vogt SK, Wozniak DF, Muglia LJ (2006) Forebrain glucocorticoid receptors modulate anxiety-associated locomotor activation and adrenal responsiveness. J Neurosci 26:1971–1978PubMedCrossRefGoogle Scholar
  27. Brambilla P, Nicoletti MA, Harenski K, Sassi RB, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC (2002) Anatomical MRI study of subgenual prefrontal cortex in bipolar and unipolar subjects. Neuropsychopharmacology 27:792–799PubMedCrossRefGoogle Scholar
  28. Bramham CR (2007) Control of synaptic consolidation in the dentate gyrus: mechanisms, functions, and therapeutic implications. Prog Brain Res 163:453–471PubMedCrossRefGoogle Scholar
  29. Bray PJ, Cotton RG (2003) Variations of the human glucocorticoid receptor gene (NR3C1): pathological and in vitro mutations and polymorphisms. Hum Mutat 21:557–568PubMedCrossRefGoogle Scholar
  30. Bremner JD, Vythilingam M, Vermetten E, Nazeer A, Adil J, Khan S, Staib LH, Charney DS (2002) Reduced volume of orbitofrontal cortex in major depression. Biol Psychiatry 51:273–279PubMedCrossRefGoogle Scholar
  31. Brent DA, Johnson BA, Perper J, Connolly J, Bridge J, Bartle S, Rather C (1994) Personality disorder, personality traits, impulsive violence, and completed suicide in adolescents. J Am Acad Child Adolesc Psychiatry 33:1080–1086PubMedCrossRefGoogle Scholar
  32. Brent DA, Bridge J, Johnson BA, Connolly J (1996) Suicidal behavior runs in families. A controlled family study of adolescent suicide victims. Arch Gen Psychiatry 53:1145–1152PubMedCrossRefGoogle Scholar
  33. Brezo J, Paris J, Barker ED, Tremblay R, Vitaro F, Zoccolillo M, Hebert M, Turecki G (2007) Natural history of suicidal behaviors in a population-based sample of young adults. Psychol Med 37:1563–1574PubMedGoogle Scholar
  34. Brody AL, Barsom MW, Bota RG, Saxena S (2001) Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. Semin Clin Neuropsychiatry 6:102–112PubMedCrossRefGoogle Scholar
  35. Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205:929–932PubMedCrossRefGoogle Scholar
  36. Caetano SC, Hatch JP, Brambilla P, Sassi RB, Nicoletti M, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC (2004) Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiatry Res 132:141–147PubMedCrossRefGoogle Scholar
  37. Carlsson A (2006) The neurochemical circuitry of schizophrenia. Pharmacopsychiatry 39(Suppl 1):S10–S14PubMedCrossRefGoogle Scholar
  38. Carlsson A (1990) Schizophrenia: a neurotransmitter imbalance syndrome? Yakubutsu Seishin Kodo 10:35–42Google Scholar
  39. Carlsson M, Carlsson A (1990) Schizophrenia: a subcortical neurotransmitter imbalance syndrome? Schizophr Bull 16:425–432PubMedCrossRefGoogle Scholar
  40. Carlsson A, Carlsson ML (2006) A dopaminergic deficit hypothesis of schizophrenia: the path to discovery. Dialogues Clin Neurosci 8:137–142PubMedGoogle Scholar
  41. Carlsson A, Waters N, Carlsson ML (1999) Neurotransmitter interactions in schizophrenia-therapeutic implications. Eur Arch Psychiatry Clin Neurosci 249(Suppl 4):37–43PubMedCrossRefGoogle Scholar
  42. Carvalho AL, Caldeira MV, Santos SD, Duarte CB (2008) Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br J Pharmacol 153(Suppl 1):S310–S324PubMedGoogle Scholar
  43. Castren E, Voikar V, Rantamaki T (2007) Role of neurotrophic factors in depression. Curr Opin Pharmacol 7:18–21PubMedCrossRefGoogle Scholar
  44. Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER, Joels M, Krugers H (2008) Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 28:6037–6045PubMedCrossRefGoogle Scholar
  45. Coffey CE, Figiel GS, Djang WT, Weiner RD (1990) Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects. Am J Psychiatry 147:187–189PubMedGoogle Scholar
  46. Compan V, Segu L, Buhot MC, Daszuta A (1998) Selective increases in serotonin 5-HT1B/1D and 5-HT2A/2C binding sites in adult rat basal ganglia following lesions of serotonergic neurons. Brain Res 793:103–111PubMedCrossRefGoogle Scholar
  47. Corbit LH, Balleine BW (2003) The role of prelimbic cortex in instrumental conditioning. Behav Brain Res 146:145–157PubMedCrossRefGoogle Scholar
  48. Daffner KR, Mesulam MM, Holcomb PJ, Calvo V, Acar D, Chabrerie A, Kikinis R, Jolesz FA, Rentz DM, Scinto LF (2000) Disruption of attention to novel events after frontal lobe injury in humans. J Neurol Neurosurg Psychiatry 68:18–24PubMedCrossRefGoogle Scholar
  49. Davis KL, Kahn RS, Ko G, Davidson M (1991) Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 148:1474–1486PubMedGoogle Scholar
  50. Daw ND, O’Doherty JP, Dayan P, Seymour B, Dolan RJ (2006) Cortical substrates for exploratory decisions in humans. Nature 441:876–879PubMedCrossRefGoogle Scholar
  51. Day M, Wokosin D, Plotkin JL, Tian X, Surmeier DJ (2008) Differential excitability and modulation of striatal medium spiny neuron dendrites. J Neurosci 28:11603–11614PubMedCrossRefGoogle Scholar
  52. de Bellis MD, Chrousos GP, Dorn LD, Burke L, Helmers K, Kling MA, Trickett PK, Putnam FW (1994) Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls. J Clin Endocrinol Metab 78:249–255PubMedCrossRefGoogle Scholar
  53. Dedovic K, Duchesne A, Andrews J, Engert V, Pruessner JC (2009) The brain and the stress axis: the neural correlates of cortisol regulation in response to stress. Neuroimage 47:864–871PubMedCrossRefGoogle Scholar
  54. di Matteo V, Pierucci M, Esposito E, Crescimanno G, Benigno A, di Giovanni G (2008) Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson’s disease and other motor disorders. Prog Brain Res 172:423–463PubMedCrossRefGoogle Scholar
  55. Diaconu G, Turecki G (2009) Family history of suicidal behavior predicts impulsive-aggressive behavior levels in psychiatric outpatients. J Affect Disord 113:172–178PubMedCrossRefGoogle Scholar
  56. Diaz Heijtz R, Kolb B, Forssberg H (2003) Can a therapeutic dose of amphetamine during pre-adolescence modify the pattern of synaptic organization in the brain? Eur J Neurosci 18:3394–3399PubMedCrossRefGoogle Scholar
  57. Diaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F (2005) Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci 25:10831–10843PubMedCrossRefGoogle Scholar
  58. Diaz-Mataix L, Artigas F, Celada P (2006) Activation of pyramidal cells in rat medial prefrontal cortex projecting to ventral tegmental area by a 5-HT1A receptor agonist. Eur Neuropsycho­pharmacol 16:288–296PubMedCrossRefGoogle Scholar
  59. Diorio D, Viau V, Meaney MJ (1993) The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress. J Neurosci 13:3839–3847PubMedGoogle Scholar
  60. Drevets WC (2007) Orbitofrontal cortex function and structure in depression. Ann N Y Acad Sci 1121:499–527PubMedCrossRefGoogle Scholar
  61. Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME (1997) Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386:824–827PubMedCrossRefGoogle Scholar
  62. Dumais A, Lesage AD, Alda M, Rouleau G, Dumont M, Chawky N, Roy M, Mann JJ, Benkelfat C, Turecki G (2005) Risk factors for suicide completion in major depression: a case–control study of impulsive and aggressive behaviors in men. Am J Psychiatry 162:2116–2124PubMedCrossRefGoogle Scholar
  63. Dutta R, Greene T, Addington J, McKenzie K, Phillips M, Murray RM (2007) Biological, life course, and cross-cultural studies all point toward the value of dimensional and developmental ratings in the classification of psychosis. Schizophr Bull 33:868–876PubMedCrossRefGoogle Scholar
  64. Duvarci S, Pare D (2007) Glucocorticoids enhance the excitability of principal basolateral amygdala neurons. J Neurosci 27:4482–4491PubMedCrossRefGoogle Scholar
  65. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 60:804–815PubMedCrossRefGoogle Scholar
  66. Ehrlich S, Breeze JL, Hesdorffer DC, Noam GG, Hong X, Alban RL, Davis SE, Renshaw PF (2005) White matter hyperintensities and their association with suicidality in depressed young adults. J Affect Disord 86:281–287PubMedCrossRefGoogle Scholar
  67. Ernst C, Deleva V, Deng X, Sequeira A, Pomarenski A, Klempan T, Ernst N, Quirion R, Gratton A, Szyf M, Turecki G (2009) Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers. Arch Gen Psychiatry 66:22–32PubMedCrossRefGoogle Scholar
  68. Evans E, Hawton K, Rodham K (2005) Suicidal phenomena and abuse in adolescents: a review of epidemiological studies. Child Abuse Negl 29:45–58PubMedCrossRefGoogle Scholar
  69. Fergusson DM, Horwood LJ, Lynskey MT (1996) Childhood sexual abuse and psychiatric disorder in young adulthood: II. Psychiatric outcomes of childhood sexual abuse. J Am Acad Child Adolesc Psychiatry 35:1365–1374PubMedCrossRefGoogle Scholar
  70. Fink JK (1997) Advances in hereditary spastic paraplegia. Curr Opin Neurol 10:313–318PubMedCrossRefGoogle Scholar
  71. Flores G, Wood GK, Liang JJ, Quirion R, Srivastava LK (1996) Enhanced amphetamine sensitivity and increased expression of dopamine D2 receptors in postpubertal rats after neonatal excitotoxic lesions of the medial prefrontal cortex. J Neurosci 16:7366–7375PubMedGoogle Scholar
  72. Freedman LJ, Insel TR, Smith Y (2000) Subcortical projections of area 25 (subgenual cortex) of the macaque monkey. J Comp Neurol 421:172–188PubMedCrossRefGoogle Scholar
  73. Fuchikami M, Morinobu S, Kurata A, Yamamoto S, Yamawaki S (2009) Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus. Int J Neuropsychopharmacol 12:73–82PubMedCrossRefGoogle Scholar
  74. Fuchs E, Flugge G, Czeh B (2006) Remodeling of neuronal networks by stress. Front Biosci 11:2746–2758PubMedCrossRefGoogle Scholar
  75. Garcia R (2001) Stress, hippocampal plasticity, and spatial learning. Synapse 40:180–183PubMedCrossRefGoogle Scholar
  76. Gareri P, de Fazio P, de Sarro G (2002) Neuropharmacology of depression in aging and age-related diseases. Ageing Res Rev 1:113–134PubMedCrossRefGoogle Scholar
  77. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ, Sibley DR Jr (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429–1432PubMedCrossRefGoogle Scholar
  78. Glowinski AL, Bucholz KK, Nelson EC, Fu Q, Madden PA, Reich W, Heath AC (2001) Suicide attempts in an adolescent female twin sample. J Am Acad Child Adolesc Psychiatry 40:1300–1307PubMedCrossRefGoogle Scholar
  79. Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H (2004) Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 61:34–41PubMedCrossRefGoogle Scholar
  80. Goodwin GM (1997) Neuropsychological and neuroimaging evidence for the involvement of the frontal lobes in depression. J Psychopharmacol 11:115–122PubMedCrossRefGoogle Scholar
  81. Goto Y, Grace AA (2008) Limbic and cortical information processing in the nucleus accumbens. Trends Neurosci 31:552–558PubMedCrossRefGoogle Scholar
  82. Graff J, Mansuy IM (2008) Epigenetic codes in cognition and behaviour. Behav Brain Res 192:70–87PubMedCrossRefGoogle Scholar
  83. Grahn JA, Parkinson JA, Owen AM (2008) The cognitive functions of the caudate nucleus. Prog Neurobiol 86:141–155PubMedCrossRefGoogle Scholar
  84. Gray JA, Roth BL (2007) Molecular targets for treating cognitive dysfunction in schizophrenia. Schizophr Bull 33:1100–1119PubMedCrossRefGoogle Scholar
  85. Graybiel AM (2008) Habits, rituals, and the evaluative brain. Annu Rev Neurosci 31:359–387PubMedCrossRefGoogle Scholar
  86. Greenwald BS, Kramer-Ginsberg E, Krishnan RR, Ashtari M, Aupperle PM, Patel M (1996) MRI signal hyperintensities in geriatric depression. Am J Psychiatry 153:1212–1215PubMedGoogle Scholar
  87. Gurevich EV, Joyce JN (1997) Alterations in the cortical serotonergic system in schizophrenia: a postmortem study. Biol Psychiatry 42:529–545PubMedCrossRefGoogle Scholar
  88. Haber SN (2003) The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 26:317–330PubMedCrossRefGoogle Scholar
  89. Haber H, Henklein P, Georgi M, Melzig MF (1995) Resolution of catecholic tetrahydroisoquinoline enantiomers and the determination of R- and S-salsolinol in biological samples by gas chromatography–mass spectrometry. J Chromatogr B Biomed Appl 672:179–187PubMedCrossRefGoogle Scholar
  90. Haber S, Fudge J, McFarland N (2000) Striatonegro striatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci 20:2369–2382PubMedGoogle Scholar
  91. Haber S, Kim K, Mailly P, Calvazara R (2006) Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J Neurosci 26:8368–8376PubMedCrossRefGoogle Scholar
  92. Hafner H, An Der Heiden W, Maurer K (2008) Evidence for separate diseases?: stages of one disease or different combinations of symptom dimensions? Eur Arch Psychiatry Clin Neurosci 258(Suppl 2):85–96PubMedCrossRefGoogle Scholar
  93. Hampton AN, Bossaerts P, O’Doherty JP (2006) The role of the ventromedial prefrontal cortex in abstract state-based inference during decision making in humans. J Neurosci 26:8360–8367PubMedCrossRefGoogle Scholar
  94. Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, Nemeroff CB (2000) Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA 284:592–597PubMedCrossRefGoogle Scholar
  95. Helmeke C, Seidel K, Poeggel G, Bredy TW, Abraham A, Braun K (2009) Paternal deprivation during infancy results in dendrite- and time-specific changes of dendritic development and spine formation in the orbitofrontal cortex of the biparental rodent Octodon degus. Neuroscience 163:790–798PubMedCrossRefGoogle Scholar
  96. Herman JP, Ostrander MM, Mueller NK, Figueiredo H (2005) Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. Prog Neuropsychopharmacol Biol Psychiatry 29:1201–1213PubMedCrossRefGoogle Scholar
  97. Hickie I, Scott E, Mitchell P, Wilhelm K, Austin MP, Bennett B (1995) Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry 37:151–160PubMedCrossRefGoogle Scholar
  98. Hickie IB, Naismith SL, Ward PB, Scott EM, Mitchell PB, Schofield PR, Scimone A, Wilhelm K, Parker G (2007) Serotonin transporter gene status predicts caudate nucleus but not amygdala or hippocampal volumes in older persons with major depression. J Affect Disord 98:137–142PubMedCrossRefGoogle Scholar
  99. Holsboer F (2000) The stress hormone system is back on the map. Curr Psychiatry Rep 2:454–456PubMedCrossRefGoogle Scholar
  100. Hoptman MJ, Gunning-Dixon FM, Murphy CF, Lim KO, Alexopoulos GS (2006) Structural neuroimaging research methods in geriatric depression. Am J Geriatr Psychiatry 14:812–822PubMedCrossRefGoogle Scholar
  101. Howes OD, Montgomery AJ, Asselin MC, Murray RM, Grasby PM, McGuire PK (2007) Molecular imaging studies of the striatal dopaminergic system in psychosis and predictions for the prodromal phase of psychosis. Br J Psychiatry Suppl 51:s13–s18PubMedCrossRefGoogle Scholar
  102. Huttunen J, Heinimaa M, Svirskis T, Nyman M, Kajander J, Forsback S, Solin O, Ilonen T, Korkeila J, Ristkari T, McGlashan T, Salokangas RK, Hietala J (2008) Striatal dopamine synthesis in first-degree relatives of patients with schizophrenia. Biol Psychiatry 63:114–117PubMedCrossRefGoogle Scholar
  103. Ichikawa J, Ishii H, Bonaccorso S, Fowler WL, O’Laughlin IA, Meltzer HY (2001) 5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem 76:1521–1531PubMedCrossRefGoogle Scholar
  104. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254PubMedCrossRefGoogle Scholar
  105. Jiao H, Zhang L, Gao F, Lou D, Zhang J, Xu M (2007) Dopamine D(1) and D(3) receptors oppositely regulate NMDA- and cocaine-induced MAPK signaling via NMDA receptor phosphorylation. J Neurochem 103:840–848PubMedCrossRefGoogle Scholar
  106. Joels M, de Kloet ER (1991) Effect of corticosteroid hormones on electrical activity in rat hippocampus. J Steroid Biochem Mol Biol 40:83–86PubMedCrossRefGoogle Scholar
  107. Jokinen J, Nordstrom P (2009) HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients. J Affect Disord 116:117–120PubMedCrossRefGoogle Scholar
  108. Jueptner M, Frith CD, Brooks DJ, Frackowiak RS, Passingham RE (1997) Anatomy of motor learning. II. Subcortical structures and learning by trial and error. J Neurophysiol 77:1325–1337PubMedGoogle Scholar
  109. Kapur S, Remington G (1996) Serotonin-dopamine interaction and its relevance to schizophrenia. Am J Psychiatry 153:466–476PubMedGoogle Scholar
  110. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109:143–148PubMedCrossRefGoogle Scholar
  111. Karst H, Nair S, Velzing E, Rumpff-Van Essen L, Slagter E, Shinnick-Gallagher P, Joels M (2002) Glucocorticoids alter calcium conductances and calcium channel subunit expression in basolateral amygdala neurons. Eur J Neurosci 16:1083–1089PubMedCrossRefGoogle Scholar
  112. Kaur S, Sassi RB, Axelson D, Nicoletti M, Brambilla P, Monkul ES, Hatch JP, Keshavan MS, Ryan N, Birmaher B, Soares JC (2005) Cingulate cortex anatomical abnormalities in children and adolescents with bipolar disorder. Am J Psychiatry 162:1637–1643PubMedCrossRefGoogle Scholar
  113. Kellendonk C, Simpson EH, Polan HJ, Malleret G, Vronskaya S, Winiger V, Moore H, Kandel ER (2006) Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 49:603–615PubMedCrossRefGoogle Scholar
  114. Kern S, Oakes TR, Stone CK, McAuliff EM, Kirschbaum C, Davidson RJ (2008) Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor. Psychoneuroendocrinology 33:517–529PubMedCrossRefGoogle Scholar
  115. Kim JJ, Haller J (2007) Glucocorticoid hyper- and hypofunction: stress effects on cognition and aggression. Ann N Y Acad Sci 1113:291–303PubMedCrossRefGoogle Scholar
  116. Kim CD, Seguin M, Therrien N, Riopel G, Chawky N, Lesage AD, Turecki G (2005) Familial aggregation of suicidal behavior: a family study of male suicide completers from the general population. Am J Psychiatry 162:1017–1019PubMedCrossRefGoogle Scholar
  117. Kim H, Shimojo S, O’Doherty JP (2006) Is avoiding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain. PLoS Biol 4:e233PubMedCrossRefGoogle Scholar
  118. Kolber BJ, Wieczorek L, Muglia LJ (2008) Hypothalamic-pituitary-adrenal axis dysregulation and behavioral analysis of mouse mutants with altered glucocorticoid or mineralocorticoid receptor function. Stress 11:321–338PubMedCrossRefGoogle Scholar
  119. Kopell BH, Greenberg BD (2008) Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry. Neurosci Biobehav Rev 32:408–422PubMedCrossRefGoogle Scholar
  120. Korz V, Frey JU (2003) Stress-related modulation of hippocampal long-term potentiation in rats: involvement of adrenal steroid receptors. J Neurosci 23:7281–7287PubMedGoogle Scholar
  121. Kretz O, Reichardt HM, Schutz G, Bock R (1999) Corticotropin-releasing hormone expression is the major target for glucocorticoid feedback-control at the hypothalamic level. Brain Res 818:488–491PubMedCrossRefGoogle Scholar
  122. Kringelbach ML, Rolls ET (2004) The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog Neurobiol 72:341–372PubMedCrossRefGoogle Scholar
  123. Krishnan KR (1993) Neuroanatomic substrates of depression in the elderly. J Geriatr Psychiatry Neurol 6:39–58PubMedGoogle Scholar
  124. Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902PubMedCrossRefGoogle Scholar
  125. Krishnan KR, Hays JC, Blazer DG (1997) MRI-defined vascular depression. Am J Psychiatry 154:497–501PubMedGoogle Scholar
  126. Kumar A, Bilker W, Jin Z, Udupa J (2000) Atrophy and high intensity lesions: complemen­­tary neurobiological mechanisms in late-life major depression. Neuropsychopharmacology 22:264–274PubMedCrossRefGoogle Scholar
  127. Kuroki T, Meltzer HY, Ichikawa J (1999) Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol Exp Ther 288:774–781PubMedGoogle Scholar
  128. Lacerda AL, Keshavan MS, Hardan AY, Yorbik O, Brambilla P, Sassi RB, Nicoletti M, Mallinger AG, Frank E, Kupfer DJ, Soares JC (2004) Anatomic evaluation of the orbitofrontal cortex in major depressive disorder. Biol Psychiatry 55:353–358PubMedCrossRefGoogle Scholar
  129. Lafer B, Renshaw PF, Sachs GS (1997) Major depression and the basal ganglia. Psychiatr Clin North Am 20:885–896PubMedCrossRefGoogle Scholar
  130. Laruelle M, Kegeles LS, Abi-Dargham A (2003) Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann N Y Acad Sci 1003:138–158PubMedCrossRefGoogle Scholar
  131. Lee SH, Payne ME, Steffens DC, McQuoid DR, Lai TJ, Provenzale JM, Krishnan KR (2003) Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression. Biol Psychiatry 54:529–533PubMedCrossRefGoogle Scholar
  132. Lehericy S, Benali H, van de Moortele PF, Pelegrini-Issac M, Waechter T, Ugurbil K, Doyon J (2005) Distinct basal ganglia territories are engaged in early and advanced motor sequence learning. Proc Natl Acad Sci U S A 102:12566–12571PubMedCrossRefGoogle Scholar
  133. Lesser IM, Boone KB, Mehringer CM, Wohl MA, Miller BL, Berman NG (1996) Cognition and white matter hyperintensities in older depressed patients. Am J Psychiatry 153:1280–1287PubMedGoogle Scholar
  134. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373:31–41PubMedCrossRefGoogle Scholar
  135. Levesque J, Eugene F, Joanette Y, Paquette V, Mensour B, Beaudoin G, Leroux JM, Bourgouin P, Beauregard M (2003) Neural circuitry underlying voluntary suppression of sadness. Biol Psychiatry 53:502–510PubMedCrossRefGoogle Scholar
  136. Li Z, Ichikawa J, Dai J, Meltzer HY (2004) Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain. Eur J Pharmacol 493:75–83PubMedCrossRefGoogle Scholar
  137. Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic- pituitary-adrenal responses to stress. Science 277:1659–1662PubMedCrossRefGoogle Scholar
  138. McEwen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54:20–23PubMedCrossRefGoogle Scholar
  139. McEwen BS, Sapolsky RM (1995) Stress and cognitive function. Curr Opin Neurobiol 5:205–216PubMedCrossRefGoogle Scholar
  140. McGirr A, Seguin M, Renaud J, Benkelfat C, Alda M, Turecki G (2006) Gender and risk factors for suicide: evidence for heterogeneity in predisposing mechanisms in a psychological autopsy study. J Clin Psychiatry 67:1612–1617PubMedCrossRefGoogle Scholar
  141. McGirr A, Paris J, Lesage A, Renaud J, Turecki G (2007) Risk factors for suicide completion in borderline personality disorder: a case–control study of cluster B comorbidity and impulsive aggression. J Clin Psychiatry 68:721–729PubMedCrossRefGoogle Scholar
  142. McGowan S, Lawrence AD, Sales T, Quested D, Grasby P (2004) Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18 F]fluorodopa study. Arch Gen Psychiatry 61:134–142PubMedCrossRefGoogle Scholar
  143. McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, Meaney MJ, Turecki G, Szyf M (2008) Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One 3:e2085PubMedCrossRefGoogle Scholar
  144. McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonte B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348PubMedCrossRefGoogle Scholar
  145. Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192PubMedCrossRefGoogle Scholar
  146. Meaney MJ, Szyf M, Seckl JR (2007) Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends Mol Med 13:269–277PubMedCrossRefGoogle Scholar
  147. Mijnster MJ, Raimundo AG, Koskuba K, Klop H, Docter GJ, Groenewegen HJ, Voorn P (1997) Regional and cellular distribution of serotonin 5-hydroxytryptamine2a receptor mRNA in the nucleus accumbens, olfactory tubercle, and caudate putamen of the rat. J Comp Neurol 389:1–11PubMedCrossRefGoogle Scholar
  148. Missale C, Fiorentini C, Busi C, Collo G, Spano PF (2006) The NMDA/D1 receptor complex as a new target in drug development. Curr Top Med Chem 6:801–808PubMedCrossRefGoogle Scholar
  149. Mitra R, Ferguson D, Sapolsky RM (2009) Mineralocorticoid receptor overexpression in basolateral amygdala reduces corticosterone secretion and anxiety. Biol Psychiatry 66:686–690PubMedCrossRefGoogle Scholar
  150. Monkul ES, Hatch JP, Nicoletti MA, Spence S, Brambilla P, Lacerda AL, Sassi RB, Mallinger AG, Keshavan MS, Soares JC (2007) Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder. Mol Psychiatry 12:360–366PubMedCrossRefGoogle Scholar
  151. Murase S, Grenhoff J, Chouvet G, Gonon FG, Svensson TH (1993) Prefrontal cortex regulates burst firing and transmitter release in rat mesolimbic dopamine neurons studied in vivo. Neurosci Lett 157:53–56PubMedCrossRefGoogle Scholar
  152. Naismith S, Hickie I, Ward PB, Turner K, Scott E, Little C, Mitchell P, Wilhelm K, Parker G (2002) Caudate nucleus volumes and genetic determinants of homocysteine metabolism in the prediction of psychomotor speed in older persons with depression. Am J Psychiatry 159:2096–2098PubMedCrossRefGoogle Scholar
  153. Nebes RD, Reynolds CF 3rd, Boada F, Meltzer CC, Fukui MB, Saxton J, Halligan EM, Dekosky ST (2002) Longitudinal increase in the volume of white matter hyperintensities in late-onset depression. Int J Geriatr Psychiatry 17:526–530PubMedCrossRefGoogle Scholar
  154. Neve KA, Seamans JK, Trantham-Davidson H (2004) Dopamine receptor signaling. J Recept Signal Transduct Res 24:165–205PubMedCrossRefGoogle Scholar
  155. Oberlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin AM (2008) Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3:97–106PubMedCrossRefGoogle Scholar
  156. Ongur D, Price JL (2000) The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 10:206–219PubMedCrossRefGoogle Scholar
  157. Ongur D, Drevets WC, Price JL (1998) Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A 95:13290–13295PubMedCrossRefGoogle Scholar
  158. Pavlides C, Watanabe Y, McEwen BS (1993) Effects of glucocorticoids on hippocampal long-term potentiation. Hippocampus 3:183–192PubMedCrossRefGoogle Scholar
  159. Pawlak V, Kerr JN (2008) Dopamine receptor activation is required for corticostriatal spike-timing-dependent plasticity. J Neurosci 28:2435–2446PubMedCrossRefGoogle Scholar
  160. Peralta V, Cuesta MJ (2001) How many and which are the psychopathological dimensions in schizophrenia? Issues influencing their ascertainment. Schizophr Res 49:269–285PubMedCrossRefGoogle Scholar
  161. Pompili M, Ehrlich S, de Pisa E, Mann JJ, Innamorati M, Cittadini A, Montagna B, Iliceto P, Romano A, Amore M, Tatarelli R, Girardi P (2007) White matter hyperintensities and their associations with suicidality in patients with major affective disorders. Eur Arch Psychiatry Clin Neurosci 257:494–499PubMedCrossRefGoogle Scholar
  162. Pompili M, Innamorati M, Mann JJ, Oquendo MA, Lester D, del Casale A, Serafini G, Rigucci S, Romano A, Tamburello A, Manfredi G, de Pisa E, Ehrlich S, Giupponi G, Amore M, Tatarelli R, Girardi P (2008) Periventricular white matter hyperintensities as predictors of suicide attempts in bipolar disorders and unipolar depression. Prog Neuropsychopharmacol Biol Psychiatry 32:1501–1507PubMedCrossRefGoogle Scholar
  163. Puig MV, Artigas F, Celada P (2005) Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA. Cereb Cortex 15:1–14PubMedCrossRefGoogle Scholar
  164. Reichardt HM, Kaestner KH, Wessely O, Gass P, Schmid W, Schutz G (1998) Analysis of glucocorticoid signalling by gene targeting. J Steroid Biochem Mol Biol 65:111–115PubMedCrossRefGoogle Scholar
  165. Reichardt HM, Tronche F, Bauer A, Schutz G (2000) Molecular genetic analysis of glucocorticoid signaling using the Cre/loxP system. Biol Chem 381:961–964PubMedCrossRefGoogle Scholar
  166. Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W, Zink M, Hortnagl H, Flor H, Henn FA, Schutz G, Gass P (2005) Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 25:6243–6250PubMedCrossRefGoogle Scholar
  167. Robinson TE, Kolb B (1999) Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci 11:1598–1604PubMedCrossRefGoogle Scholar
  168. Rogers MA, Bradshaw JL, Pantelis C, Phillips JG (1998) Frontostriatal deficits in unipolar major depression. Brain Res Bull 47:297–310PubMedCrossRefGoogle Scholar
  169. Rollema H, Lu Y, Schmidt AW, Zorn SH (1997) Clozapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation. Eur J Pharmacol 338:R3–R5PubMedCrossRefGoogle Scholar
  170. Rollema H, Lu Y, Schmidt AW, Sprouse JS, Zorn SH (2000) 5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. Biol Psychiatry 48:229–237PubMedCrossRefGoogle Scholar
  171. Roth TL, Lubin FD, Funk AJ, Sweatt JD (2009) Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry 65:760–769PubMedCrossRefGoogle Scholar
  172. Roy A, Segal NL, Centerwall BS, Robinette CD (1991) Suicide in twins. Arch Gen Psychiatry 48:29–32PubMedCrossRefGoogle Scholar
  173. Roy A, Segal NL, Sarchiapone M (1995) Attempted suicide among living co-twins of twin suicide victims. Am J Psychiatry 152:1075–1076PubMedGoogle Scholar
  174. Saint-Cyr JA, Taylor AE, Nicholson K (1995) Behavior and the basal ganglia. Adv Neurol 65:1–28PubMedGoogle Scholar
  175. Salloway S, Malloy P, Kohn R, Gillard E, Duffy J, Rogg J, Tung G, Richardson E, Thomas C, Westlake R (1996) MRI and neuropsychological differences in early- and late-life-onset geriatric depression. Neurology 46:1567–1574PubMedCrossRefGoogle Scholar
  176. Schulsinger F, Kety SS, Rosenthal D, Wender PH (1979) A family study of suicide. In: Schou M, Stromgren E (eds) Origins, prevention and treatment of affective disorders. Academic, OrlandoGoogle Scholar
  177. Seamans JK, Yang CR (2004) The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol 74:1–58PubMedCrossRefGoogle Scholar
  178. Segal M, Greenberger V, Korkotian E (2003) Formation of dendritic spines in cultured striatal neurons depends on excitatory afferent activity. Eur J Neurosci 17:2573–2585PubMedCrossRefGoogle Scholar
  179. Seguin M, Lesage A, Turecki G, Bouchard M, Chawky N, Tremblay N, Daigle F, Guy A (2007) Life trajectories and burden of adversity: mapping the developmental profiles of suicide mortality. Psychol Med 37:1575–1583PubMedCrossRefGoogle Scholar
  180. Sesack SR, Carr DB, Omelchenko N, Pinto A (2003) Anatomical substrates for glutamate-dopamine interactions: evidence for specificity of connections and extrasynaptic actions. Ann N Y Acad Sci 1003:36–52PubMedCrossRefGoogle Scholar
  181. Shah PJ, Glabus MF, Goodwin GM, Ebmeier KP (2002) Chronic, treatment-resistant depression and right fronto-striatal atrophy. Br J Psychiatry 180:434–440PubMedCrossRefGoogle Scholar
  182. Shen H, Sesack SR, Toda S, Kalivas PW (2008) Automated quantification of dendritic spine density and spine head diameter in medium spiny neurons of the nucleus accumbens. Brain Struct Funct 213:149–157PubMedCrossRefGoogle Scholar
  183. Soares JC, Mann JJ (1997) The anatomy of mood disorders – review of structural neuroimaging studies. Biol Psychiatry 41:86–106PubMedCrossRefGoogle Scholar
  184. Spokas M, Wenzel A, Stirman SW, Brown GK, Beck AT (2009) Suicide risk factors and mediators between childhood sexual abuse and suicide ideation among male and female suicide attempters. J Trauma Stress 22:467–470PubMedCrossRefGoogle Scholar
  185. Stahl SM (2007a) Beyond the dopamine hypothesis to the NMDA glutamate receptor hypofunction hypothesis of schizophrenia. CNS Spectr 12:265–268PubMedGoogle Scholar
  186. Stahl SM (2007b) Novel therapeutics for depression: L-methylfolate as a trimonoamine modulator and antidepressant-augmenting agent. CNS Spectr 12:739–744PubMedGoogle Scholar
  187. Statham DJ, Heath AC, Madden PA, Bucholz KK, Bierut L, Dinwiddie SH, Slutske WS, Dunne MP, Martin NG (1998) Suicidal behaviour: an epidemiological and genetic study. Psychol Med 28:839–855PubMedCrossRefGoogle Scholar
  188. Steffens DC, Helms MJ, Krishnan KR, Burke GL (1999) Cerebrovascular disease and depression symptoms in the cardiovascular health study. Stroke 30:2159–2166PubMedCrossRefGoogle Scholar
  189. Stephan KE, Friston KJ, Frith CD (2009) Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 35:509–527PubMedCrossRefGoogle Scholar
  190. Strakowski SM, Adler CM, Delbello MP (2002) Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder? Bipolar Disord 4:80–88PubMedCrossRefGoogle Scholar
  191. Szyf M, Weaver I, Meaney M (2007) Maternal care, the epigenome and phenotypic differences in behavior. Reprod Toxicol 24:9–19PubMedCrossRefGoogle Scholar
  192. Tanaka T, Naquet R (1976) Influence of subcortical stimulation on amygdaloid kindled cats. Appl Neurophysiol 39:302–305PubMedGoogle Scholar
  193. Tanaka SC, Doya K, Okada G, Ueda K, Okamoto Y, Yamawaki S (2004) Prediction of immediate and future rewards differentially recruits cortico-basal ganglia loops. Nat Neurosci 7:887–893PubMedCrossRefGoogle Scholar
  194. Tata DA, Anderson BJ (2010) The effects of chronic glucocorticoid exposure on dendritic length, synapse numbers and glial volume in animal models: implications for hippocampal volume reductions in depression. Physiol Behav 99:186–193PubMedCrossRefGoogle Scholar
  195. Tata DA, Marciano VA, Anderson BJ (2006) Synapse loss from chronically elevated glucocorticoids: relationship to neuropil volume and cell number in hippocampal area CA3. J Comp Neurol 498:363–374PubMedCrossRefGoogle Scholar
  196. Taylor SF, Liberzon I (2007) Neural correlates of emotion regulation in psychopathology. Trends Cogn Sci 11:413–418PubMedCrossRefGoogle Scholar
  197. Thomas AJ, Perry R, Barber R, Kalaria RN, O’Brien JT (2002) Pathologies and pathological mechanisms for white matter hyperintensities in depression. Ann N Y Acad Sci 977:333–339PubMedCrossRefGoogle Scholar
  198. Treadway MT, Grant MM, Ding Z, Hollon SD, Gore JC, Shelton RC (2009) Early adverse events, HPA activity and rostral anterior cingulate volume in MDD. PLoS One 4:e4887PubMedCrossRefGoogle Scholar
  199. Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban PC, Bock R, Klein R, Schutz G (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23:99–103PubMedCrossRefGoogle Scholar
  200. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525PubMedCrossRefGoogle Scholar
  201. Tseng KY, O’Donnell P (2004) Dopamine-glutamate interactions controlling prefrontal cortical pyramidal cell excitability involve multiple signaling mechanisms. J Neurosci 24:5131–5139PubMedCrossRefGoogle Scholar
  202. Tupler LA, Krishnan KR, McDonald WM, Dombeck CB, D’Souza S, Steffens DC (2002) Anatomic location and laterality of MRI signal hyperintensities in late-life depression. J Psychosom Res 53:665–676PubMedCrossRefGoogle Scholar
  203. Turner JD, Muller CP (2005) Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple new human exon 1. J Mol Endocrinol 35:283–292PubMedCrossRefGoogle Scholar
  204. Turner JD, Schote AB, Macedo JA, Pelascini LP, Muller CP (2006) Tissue specific glucocorticoid receptor expression, a role for alternative first exon usage? Biochem Pharmacol 72:1529–1537PubMedCrossRefGoogle Scholar
  205. Valentin VV, Dickinson A, O’Doherty JP (2007) Determining the neural substrates of goal-directed learning in the human brain. J Neurosci 27:4019–4026PubMedCrossRefGoogle Scholar
  206. van Elst LT, Woermann FG, Lemieux L, Thompson PJ, Trimble MR (2000) Affective aggression in patients with temporal lobe epilepsy: a quantitative MRI study of the amygdala. Brain 123(Pt 2):234–243PubMedCrossRefGoogle Scholar
  207. van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L (2009) A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol Med 39:179–195PubMedCrossRefGoogle Scholar
  208. Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, Brummer M, Staib L, Vermetten E, Charney DS, Nemeroff CB, Bremner JD (2002) Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry 159:2072–2080PubMedCrossRefGoogle Scholar
  209. Weaver IC (2009) Epigenetic effects of glucocorticoids. Semin Fetal Neonatal Med 14:143–150PubMedCrossRefGoogle Scholar
  210. Weaver ICG, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854PubMedCrossRefGoogle Scholar
  211. Wender PH, Kety SS, Rosenthal D, Schulsinger F, Ortmann J, Lunde I (1986) Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry 43:923–929PubMedCrossRefGoogle Scholar
  212. Widom CS, Dumont K, Czaja SJ (2007) A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up. Arch Gen Psychiatry 64:49–56PubMedCrossRefGoogle Scholar
  213. Williams GV, Goldman-Rakic PS (1995) Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376:572–575PubMedCrossRefGoogle Scholar
  214. Yamada K, McEwen BS, Pavlides C (2003) Site and time dependent effects of acute stress on hippocampal long-term potentiation in freely behaving rats. Exp Brain Res 152:52–59PubMedCrossRefGoogle Scholar
  215. Yasuno F, Suhara T, Ichimiya T, Takano A, Ando T, Okubo Y (2004) Decreased 5-HT1A receptor binding in amygdala of schizophrenia. Biol Psychiatry 55:439–444PubMedCrossRefGoogle Scholar
  216. Yin HH, Knowlton BJ, Balleine BW (2005a) Blockade of NMDA receptors in the dorsomedial striatum prevents action-outcome learning in instrumental conditioning. Eur J Neurosci 22:505–512PubMedCrossRefGoogle Scholar
  217. Yin HH, Ostlund SB, Knowlton BJ, Balleine BW (2005b) The role of the dorsomedial striatum in instrumental conditioning. Eur J Neurosci 22:513–523PubMedCrossRefGoogle Scholar
  218. Yin HH, Knowlton BJ, Balleine BW (2006) Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning. Behav Brain Res 166:189–196PubMedCrossRefGoogle Scholar
  219. Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z (2005) Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism. J Neurosci 25:5488–5501PubMedCrossRefGoogle Scholar
  220. Zhong P, Yuen EY, Yan Z (2008) Modulation of neuronal excitability by serotonin-NMDA interactions in prefrontal cortex. Mol Cell Neurosci 38:290–299PubMedCrossRefGoogle Scholar
  221. Zhu MY, Wang WP, Huang J, Regunathan S (2007) Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. J Neurochem 103:1811–1820PubMedCrossRefGoogle Scholar
  222. Zou B, Golarai G, Connor JA, Tang AC (2001) Neonatal exposure to a novel environment enhances the effects of corticosterone on neuronal excitability and plasticity in adult hippocampus. Brain Res Dev Brain Res 130:1–7PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Maxwell Bennett
    • 1
  1. 1.Brain and Mind Research InstituteCamperdownAustralia

Personalised recommendations