Neurobiological Markers of Familial Risk for Depression

  • Lara C. Foland-Ross
  • Michael G. Hardin
  • Ian H. GotlibEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 14)


Major depression is associated with a wide range of neurobiological disturbances, including anomalies in the structure and function of cortical and subcortical gray matter and dysregulation of the HPA axis. In this chapter, we review research demonstrating that many of these abnormalities are also present in never-depressed offspring of adults with recurrent depression and discuss how such findings might reflect dysfunctional neuroregulatory systems that precede the onset of this disorder. We also briefly discuss candidate genes and environmental factors that have been posited to be directly involved in the transmission of neural and HPA-axis abnormalities from depressed parents to their offspring, and we review how, by obtaining a better understanding of the neurobiological markers of depression risk, we can facilitate the development of targeted strategies for the prevention and treatment of major depression.


Depression Risk Neuroimaging Cortisol Hippocampus DLPFC Amygdala Genetics 



Preparation of this chapter was facilitated by NIMH Grants MH59259 and MH74849 to Ian H. Gotlib and MH090617 to Lara Foland-Ross, and by a Hope for Depression Research Foundation Grant awarded to Ian H. Gotlib and Lara Foland-Ross.


  1. Adam EK, Doane LD, Zinbarg RE, Mineka S, Craske MG, Griffith JW (2010) Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence. Psychoneuroendocrinology 35(6):921–931CrossRefPubMedGoogle Scholar
  2. Adolphs R (2008) Fear, faces, and the human amygdala. Curr Opin Neurobiol 18(2):166–172CrossRefPubMedGoogle Scholar
  3. Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381CrossRefPubMedGoogle Scholar
  4. Amico F, Meisenzahl E, Koutsouleris N, Reiser M, Moller HJ, Frodl T (2011) Structural MRI correlates for vulnerability and resilience to major depressive disorder. J Psychiatry Neurosci 36(1):15–22CrossRefPubMedGoogle Scholar
  5. Aron AR (2011) From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses. Biol Psychiatry 69(12):e55–e68CrossRefGoogle Scholar
  6. Baaré WF, Vinberg M, Knudsen GM, Paulson OB, Langkilde AR, Jernigan TL, Kessing LV (2010) Hippocampal volume changes in healthy subjects at risk of unipolar depression. J Psychiatr Res 44(10):655–662CrossRefPubMedGoogle Scholar
  7. Barbazanges A, Vallée M, Mayo W, Day J, Simon H, Le Moal M, Maccari S (1996) Early and later adoptions have different long-term effects on male rat offspring. J Neurosci 16(23):7783–7790PubMedGoogle Scholar
  8. Beardslee WR, Versage EM, Gladstone TR (1998) Children of affectively ill parents: a review of the last 10 years. J Am Acad Child Adolesc Psychiatry 37(11):11134–11141Google Scholar
  9. Beauregard M, Levesque J, Bourgouin P (2001) Neural correlates of conscious self-regulation of emotion. J Neurosci 21(18):RC165Google Scholar
  10. Bhagwagar Z, Hafizi S, Cowen PJ (2005) Increased salivary cortisol after waking in depression. Psychopharmacologia 182(1):54–57CrossRefGoogle Scholar
  11. Browning M, Holmes EA, Harmer CJ (2010) The modification of attentional bias to emotional information: a review of the techniques, mechanisms, and relevance to emotional disorders. Cogn Affect Behav Neurosci 10(1):8–20CrossRefPubMedGoogle Scholar
  12. Bueller JA, Aftab M, Sen S, Gomez-Hassan D, Burmeister M, Zubieta JK (2006) BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biol Psychiatry 59(9):812–815CrossRefPubMedGoogle Scholar
  13. Burke HM, Davis MC, Otte C, Mohr DC (2005) Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology 30(9):846–856CrossRefPubMedGoogle Scholar
  14. Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ (1998) Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Nat Acad Sci USA 95(9):5335–5340CrossRefPubMedGoogle Scholar
  15. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386–389CrossRefPubMedGoogle Scholar
  16. Chen MC, Hamilton JP, Gotlib IH (2010) Decreased hippocampal volume in healthy girls at risk of depression. Arch Gen Psychiatry 67(3):270–276CrossRefPubMedGoogle Scholar
  17. Chao HM, Choo PH, McEwen BS (1989) Glucocorticoid and mineralocorticoid receptor mRNA expression in rat brain. Neuroendocrinology 50(4):365–371CrossRefPubMedGoogle Scholar
  18. Critchley H, Daly E, Phillips M, Brammer M, Bullmore E, Williams S, Van Amelsvoort T, Robertson D, David A, Murphy D (2000) Explicit and implicit neural mechanisms for processing of social information from facial expressions: a functional magnetic resonance imaging study. Hum Brain Mapp 9(2):93–105CrossRefPubMedGoogle Scholar
  19. Dannlowski U, Konrad C, Kugel H, Zwitserlood P, Domschke K, Schöning S, Ohrmann P, Bauer J, Pyka M, Hohoff C, Zhang W, Baune BT, Heindel W, Arolt V, Suslow T (2010) Emotion specific modulation of automatic amygdala responses by 5-HTTLPR genotype. Neuroimage 53(3):893–898CrossRefPubMedGoogle Scholar
  20. De Raedt R, Koster EH, Joormann J (2010) Attentional control in depression: a translational affective neuroscience approach. Cogn Affect Behav Neurosci 10(1):1–7CrossRefPubMedGoogle Scholar
  21. Dearing KF, Gotlib IH (2009) Interpretation of ambiguous information in girls at risk for depression. J Abnorm Child Psychol 37(1):79–91CrossRefPubMedGoogle Scholar
  22. Dickerson SS, Kemeny ME (2004) Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull 130(3):355–391CrossRefPubMedGoogle Scholar
  23. Diego MA, Field T, Hernandez-Reif M, Cullen C, Schanberg S, Kuhn C (2004) Prepartum, postpartum, and chronic depression effects on newborns. Psychiatry 67(1):63–80PubMedGoogle Scholar
  24. Dougherty LR, Klein DN, Congdon E, Canli T, Hayden EP (2010) Interaction between 5-HTTLPR and BDNF Val66Met polymorphisms on HPA axis reactivity in preschoolers. Biol Psychiatry 83(2):93–100Google Scholar
  25. Dozier M, Peloso E, Lewis E, Laurenceau JP, Levine S (2008) Effects of an attachment-based intervention on the cortisol production of infants and toddlers in foster care. Dev Psychopathol 20(3):845–859CrossRefPubMedGoogle Scholar
  26. Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59(12):1116–1127CrossRefPubMedGoogle Scholar
  27. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112(2):257–269CrossRefPubMedGoogle Scholar
  28. Eisenberger NI, Gable SL, Lieberman MD (2007) Functional magnetic resonance imaging responses relate to differences in real-world social experience. Emotion 7(4):745–754CrossRefPubMedGoogle Scholar
  29. Evans J, Heron J, Francomb H, Oke S, Golding J (2001) Cohort study of depressed mood during pregnancy and after childbirth. BMJ 323(7307):257–260CrossRefPubMedGoogle Scholar
  30. Feldman S, Conforti N, Siegel RA (1982) Adrenocortical responses following limbic stimulation in rats with hypothalamic deafferentations. Neuroendocrinology 35:205CrossRefPubMedGoogle Scholar
  31. Field T (1984) Early interactions between infants and their postpartum depressed mothers. Infant Behav Dev 7(4):537–540CrossRefGoogle Scholar
  32. Field T (1994) The effects of mother’s physical and emotional unavailability on emotion regulation. The development of emotion regulation. N. A. Fox Chicago, University of Chicago PressGoogle Scholar
  33. Field T, Diego M, Dieter J, Hernandez-Reif M, Schanberg S, Kuhn C, Yando R, Bendell D (2006a) Prenatal depression effects on the fetus and newborn: a review. Infant Behav Dev 29(3):445–455CrossRefGoogle Scholar
  34. Field T, Hernandez-Reif M, Diego M, Figueiredo B, Schanberg S, Kuhn C (2006b) Prenatal cortisol, prematurity and low birthweight. Infant Behav Dev 29(2):268–275CrossRefGoogle Scholar
  35. Forbes EE, Hariri AR, Martin SL, Silk JS, Moyles DL, Fisher PM, Brown SM, Ryan ND, Birmaher B, Axelson DA, Dahl RE (2009) Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. Am J Psychiatry 166(1):64–73CrossRefPubMedGoogle Scholar
  36. Forbes EE, Shaw DS, Dahl RE (2007) Alterations in reward-related decision making in boys with recent and future depression. Biol Psychiatry 61(5):633–639CrossRefPubMedGoogle Scholar
  37. Fries E, Dettenborn L, Kirschbaum C (2009) The cortisol awakening response (CAR): facts and future directions. Int J Psychophysiol 72(1):67–73CrossRefPubMedGoogle Scholar
  38. Frodl T, Schüle C, Schmitt G, Born C, Baghai T, Zill P, Bottlender R, Rupprecht R, Bondy B, Reiser M, Möller HJ, Meisenzahl EM (2007) Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry 64(4):410–416CrossRefPubMedGoogle Scholar
  39. Furay AR, Bruestle AE, Herman JP (2008) The role of the forebrain glucocorticoid receptor in acute and chronic stress. Endocrinology 149(11):5482–5490CrossRefPubMedGoogle Scholar
  40. Furman DJ, Hamilton JP, Joormann J, Gotlib IH (2010) Altered timing of amygdala activation during sad mood elaboration as a function of 5-HTTLPR. Soc Cogn Affect Neurosci 6(3):270–276CrossRefPubMedGoogle Scholar
  41. Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S, Benedetti F, Abbamonte M, Gasparotti R, Barale F, Perez J, McGuire P, Politi P (2009) Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci 34(6):418–432PubMedGoogle Scholar
  42. Gallagher P, Reid KS, Ferrier IN (2009) Neuropsychological functioning in health and mood disorder: modulation by glucocorticoids and their receptors. Psychoneuroendocrinology 34(Suppl 1):S196–S207CrossRefPubMedGoogle Scholar
  43. Gatt JM, Nemeroff CB, Dobson-Stone C, Paul RH, Bryant RA, Schofield PR, Gordon E, Kemp AH, Williams LM (2009) Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol Psychiatry 14(7):681–695CrossRefPubMedGoogle Scholar
  44. Gerritsen L, Tendolkar I, Franke B, Vasquez AA, Kooijman S, Buitelaar J, Fernández G, Rijpkema M (in press) BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects. Mol PsychiatryGoogle Scholar
  45. Gitau R, Fisk NM, Teixeira JM, Cameron A, Glover V (2001) Fetal hypothalamic-pituitaryadrenal stress responses to invasive procedures are independent of maternal responses. J Clin Endocrinol Metab 86(1):104–109CrossRefPubMedGoogle Scholar
  46. Glover V (1997) Maternal stress or anxiety in pregnancy and emotional development of the child. Br J Psychiatry 171:105–106CrossRefPubMedGoogle Scholar
  47. Gold GI (2003) Linking reward expectation to behavior in the basal ganglia. Trends Neurosci 26(1):12–14CrossRefPubMedGoogle Scholar
  48. Goodman SH, Gotlib IH (1999) Risk for psychopathology in the children of depressed mothers: a developmental model for understanding mechanisms of transmission. Psychol Rev 106(3):458–490CrossRefPubMedGoogle Scholar
  49. Goodyer IM, Bacon A, Ban M, Croudace T, Herbert J (2009) Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents. Br J Psychiatry 195(1):39–45CrossRefPubMedGoogle Scholar
  50. Goodyer IM, Tamplin A, Herbert J, Altham PM (2000) Recent life events, cortisol, dehydroepiandrosterone and the onset of major depression in high-risk adolescents. Br J Psychiatry 177:499–504CrossRefPubMedGoogle Scholar
  51. Gotlib IH, Hamilton JP (2008) Neuroimaging and depression: current status and unresolved issues. Curr Dir Psychol Sci 17(2):159–163CrossRefGoogle Scholar
  52. Gotlib IH, Hamilton JP, Cooney RE, Singh MK, Henry ML, Joormann J (2010) Neural processing of reward and loss in girls at risk for major depression. Arch Gen Psychiatry 67(4):380–387CrossRefPubMedGoogle Scholar
  53. Gotlib IH, Joormann J, Minor KL, Hallmayer J (2008) HPA-axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biol Psychiatry 63(9):847–851CrossRefPubMedGoogle Scholar
  54. Gotthardt U, Schweiger U, Fahrenberg J, Lauer CJ, Holsboer F, Heuser I (1995) Cortisol, ACTH, and cardiovascular response to a cognitive challenge paradigm in aging and depression. Am J Physiol 268(Pt 4):R865–R873PubMedGoogle Scholar
  55. Halligan SL, Herbert J, Goodyer I, Murray L (2007) Disturbances in morning cortisol secretion in association with maternal postnatal depression predict subsequent depressive symptomatology in adolescents. Biol Psychiatry 62(1):40–46CrossRefPubMedGoogle Scholar
  56. Halligan SL, Herbert J, Goodyer IM, Murray L (2004) Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biol Psychiatry 55(4):376–381CrossRefPubMedGoogle Scholar
  57. Hamilton JP, Siemer M, Gotlib IH (2008) Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Mol Psychiatry 13(11):993–1000CrossRefPubMedGoogle Scholar
  58. Hammen C, Shih J, Altman T, Brennan PA (2003) Interpersonal impairment and the prediction of depressive symptoms in adolescent children of depressed and nondepressed mothers. J Am Acad Child Adolesc Psychiatry 42(5):571–577CrossRefPubMedGoogle Scholar
  59. Hanson JL, Chung MK, Avants BB, Shirtcliff EA, Gee JC, Davidson RJ, Pollak SD (2010) Early stress is associated with alterations in the orbitofrontal cortex: a tensor-based morphometry investigation of brain structure and behavioral risk. J Neurosci 30(22):7466–7472CrossRefPubMedGoogle Scholar
  60. Hariri AR, Bookheimer SY, Mazziotta JC (2000) Modulating emotional responses: effects of a neocortical network on the limbic system. NeuroReport 11(1):43–48CrossRefPubMedGoogle Scholar
  61. Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR (2005) A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 62(2):146–152CrossRefPubMedGoogle Scholar
  62. Harris TO, Borsanyi S, Messari S, Stanford K, Brown GW, Cleary SE, Shiers HM, Herbert J (2000) Morning cortisol as a risk factor for subsequent major depressive disorder in adult women. Br J Psychiatry 177:505–510CrossRefPubMedGoogle Scholar
  63. Heim C, Mletzko T, Purselle D, Musselman DL, Nemeroff CB (2008) The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biol Psychiatry 63(4):398–405CrossRefPubMedGoogle Scholar
  64. 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. J Am Med Assoc 284(5):592–597CrossRefGoogle Scholar
  65. Heim C, Newport DJ, Wagner D, Wilcox MM, Miller AH, Nemeroff CB (2002) The role of early adverse experience and adulthood stress in the prediction of neuroendocrine stress reactivity in women: a multiple regression analysis. Depress Anxiety 15(3):117–125CrossRefPubMedGoogle Scholar
  66. Herman JP, Ostrander MM, Mueller NK, Figueiredo H (2005) Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. Prog Neuropsychopharmacol Biol Psychiatry 29(8):1201–1213CrossRefPubMedGoogle Scholar
  67. Herman JP, Schäfer MK, Young EA, Thompson R, Douglass J, Akil H, Watson SJ (1989) Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis. J Neurosci 9(9):3072–3082PubMedGoogle Scholar
  68. Heuser I, Yassouridis A, Holsboer F (1994) The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res 28(4):341–356CrossRefPubMedGoogle Scholar
  69. Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736CrossRefPubMedGoogle Scholar
  70. Huang H, Fan X, Williamson DE, Rao U (2011) White matter changes in healthy adolescents at familial risk for unipolar depression: a diffusion tensor imaging study. Neuropsychopharmacology 36(3):684–691CrossRefPubMedGoogle Scholar
  71. Huber TJ, Issa K, Schik G, Wolf OT (2006) The cortisol awakening response is blunted in psychotherapy inpatients suffering from depression. Psychoneuroendocrinology 31(7):900–904CrossRefPubMedGoogle Scholar
  72. Huot RL, Gonzalez ME, Ladd CO, Thrivikraman KV, Plotsky PM (2004) Foster litters prevent hypothalamic-pituitary-adrenal axis sensitization mediated by neonatal maternal separation. Psychoneuroendocrinology 29(2):279–289CrossRefPubMedGoogle Scholar
  73. Joormann J, Cooney RE, Henry ML, Gotlib IH (2012) Neural correlates of automatic mood regulation in girls at high risk for depression. J Abnorm Psychol 121(1):61–72CrossRefPubMedGoogle Scholar
  74. Joormann J, Gilbert K, Gotlib IH (2010) Emotion identification in girls at high risk for depression. J Child Psychol Psychiatry 51(5):575–582CrossRefPubMedGoogle Scholar
  75. Joormann J, Talbot L, Gotlib IH (2007) Biased processing of emotional information in girls at risk for depression. J Abnorm Psychol 116(1):135–143CrossRefPubMedGoogle Scholar
  76. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatric Research 109(2):143–148CrossRefGoogle Scholar
  77. Kaufman J, Yang BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter J (2006) Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biol Psychiatry 59(8):673–680CrossRefPubMedGoogle Scholar
  78. Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J (2004) Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Nat Acad Sci USA 101(49):17316–17321CrossRefPubMedGoogle Scholar
  79. Kawagoe R, Takikawa Y, Hikosaka O (1998) Expectation of reward modulates cognitive signals in the basal ganglia. Nat Neurosci 1(5):411–416CrossRefPubMedGoogle Scholar
  80. Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC (2011) Structural neuroimaging studies in major depressive disorder: meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry 68(7):675–690CrossRefPubMedGoogle Scholar
  81. Kensinger EA, Corkin S (2004) Two routes to emotional memory: distinct neural processes for valence and arousal. Proc Nat Acad Sci USA 101(9):3310–3315CrossRefPubMedGoogle Scholar
  82. Kessler RC, Wang PS (2009) Epidemiology of depression. In: Gotlib IH, Hammen CL (eds) Handbook of depression, 2nd edn. Guilford, New YorkGoogle Scholar
  83. Kieseppä T, Eerola M, Mäntylä R, Neuvonen T, Poutanen V, Luoma K, Tuulio-Henriksson A, Jylhä P, Mantere O, Melartin T, Rytsälä H, Vuorilehto M, Isometsä E (2010) Major depressive disorder and white matter abnormalities: a diffusion tensor imaging study with tract-based spatial statistics. J Affect Disord 120(1–3):240–244CrossRefPubMedGoogle Scholar
  84. Knorr U, Vinberg M, Kessing LV, Wetterslev J (2010) Salivary cortisol in depressed patients versus control persons: a systematic review and meta-analysis. Psychoneuroendocrinology 35(9):1275–1286CrossRefPubMedGoogle Scholar
  85. Koolschijn PC, van Haren NE, Lensvelt-Mulders GJ, Hulshoff Pol HE, Kahn RS (2009) Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 30(11):3719–3735CrossRefPubMedGoogle Scholar
  86. Kumar P, Waiter G, Ahearn T, Milders M, Reid I, Steele JD (2008) Abnormal temporal difference reward-learning signals in major depression. Brain 131(Pt 8):2084–2093CrossRefPubMedGoogle Scholar
  87. Lai CH, Hsu YY, Wu YT (2010) First episode drug-naive major depressive disorder with panic disorder: gray matter deficits in limbic and default network structures. Eur Neuropsychopharmacol 20(10):676–682CrossRefPubMedGoogle Scholar
  88. Langrock AM, Compas BE, Keller G, Merchant MJ, Copeland ME (2002) Coping with the stress of parental depression: parents’ reports of children’s coping, emotional, and behavioral problems. J Clin Child Adolesc Psychol 31(3):312–324PubMedGoogle Scholar
  89. Lau JY, Eley TC (2008) Disentangling gene-environment correlations and interactions on adolescent depressive symptoms. J Child Adolesc Psychiatry 49(2):142–150CrossRefGoogle Scholar
  90. Lau JYF, Rijsdijk FV, Eley TC (2006) I think, therefore I am: a twin study of attributional style in adolescents. J Child Psychol Psychiatry 47:696–703CrossRefPubMedGoogle Scholar
  91. Lévesque ML, Beauregard M, Ottenhof KW, Fortier E, Tremblay RE, Brendgen M, Pérusse D, Dionne G, Robaey P, Vitaro F, Boivin M, Booij L (2011) Altered patterns of brain activity during transient sadness in children at familial risk for major depression. J Affect Disord 135(1–3):410–413CrossRefPubMedGoogle Scholar
  92. Levinson DF (2006) The genetics of depression: a review. Biol Psychiatry 60(2):84–92CrossRefPubMedGoogle Scholar
  93. Liu D, Diorio J, Day JC, Francis DD, Meaney MJ (2000) Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci 3(8):799–806CrossRefPubMedGoogle Scholar
  94. Lopez JF, Akil H, Watson SJ (1999) Neural circuits mediating stress. Biol Psychiatry 46(11):1461–1471CrossRefPubMedGoogle Scholar
  95. Lundy BL, Jones NA, Field T, Nearing G, Davalos M, Pietro PA, Schanberg S, Kuhn C (1999) Prenatal depression effects on neonates. Infant Behav Dev 22(1):119–129CrossRefGoogle Scholar
  96. Lupien SJ, King S, Meaney MJ, McEwen BS (2000) Child’s stress hormone levels correlate with mother’s socioeconomic status and depressive state. Biol Psychiatry 48(10):976–980CrossRefPubMedGoogle Scholar
  97. Lupien SJ, Parent S, Evans AC, Tremblay RE, Zelazo PD, Corbo V, Pruessner JC, Séguin JR (2011) Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proc Nat Acad Sci USA 108(34):14324–14329CrossRefPubMedGoogle Scholar
  98. Maccari S, Piazza PV, Kabbaj M, Barbazanges A, Simon H, Le Moal M (1995) Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress. J Neurosci 15(1):110–116PubMedGoogle Scholar
  99. Magariños AM, Deslandes A, McEwen BS (1999) Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress. Eur J Pharmacol 371(2–3):113–122CrossRefPubMedGoogle Scholar
  100. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110PubMedGoogle Scholar
  101. Mannie ZN, Bristow GC, Harmer CJ, Cowen PJ (2007a) Impaired emotional categorisation in young people at increased familial risk of depression. Neuropsychologia 45(13):2975–2980CrossRefGoogle Scholar
  102. Mannie ZN, Harmer CJ, Cowen PJ (2007b) Increased waking salivary cortisol levels in young people at familial risk of depression. Am J Psychiatry 164(4):617–621CrossRefGoogle Scholar
  103. Mannie ZN, Taylor MJ, Harmer CJ, Cowen PJ, Norbury R (2011) Frontolimbic responses to emotional faces in young people at familial risk of depression. J Affect Disord 130(1–2):127–132CrossRefPubMedGoogle Scholar
  104. McEwen BS (1998) Protective and damaging effects of stress mediators. N Engl J Med 338(3):171–179CrossRefPubMedGoogle Scholar
  105. McEwen BS, Conrad CD, Kuroda Y, Frankfurt M, Magarinos AM, McKittrick C (1997) Prevention of stress-induced morphological and cognitive consequences. Eur Neuropsychopharmacol 7(3):S323–S328CrossRefPubMedGoogle Scholar
  106. Mehta MA, Golembo NI, Nosarti C, Colvert E, Mota A, Williams SC, Rutter M, Sonuga-Barke EJ (2009) Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian adoptees study pilot. J Child Psychol Psychiatry 50(8):943–951CrossRefPubMedGoogle Scholar
  107. Mizoguchi K, Ishige A, Aburada M, Tabira T (2003) Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus. Neuroscience 119(3):887–897CrossRefPubMedGoogle Scholar
  108. Monk CS, Klein RG, Telzer EH, Schroth EA, Mannuzza S, Moulton JL III, Guardino M, Masten CL, McClure-Tone EB, Fromm S, Blair RJ, Pine DS, Ernst M (2008) Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression. Am J Psychiatry 165(1):90–98CrossRefPubMedGoogle Scholar
  109. Monroe SM, Simons AD (1991) Diathesis-stress theories in the context of life stress research: implications for the depressive disorders. Psychol Bull 110(3):406–425CrossRefPubMedGoogle Scholar
  110. Murer MG, Yan Q, Raisman-Vozari R (2001) Brain-derived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease. Prog Neurobiol 63(1):71–124CrossRefPubMedGoogle Scholar
  111. Murray C, Lobez A (1996) The global burden of disease. Harvard School of Public Health, CambridgeGoogle Scholar
  112. Murray L, Cooper P (2003) Intergenerational transmission of affective and cognitive processes asociated with depression: infancy and the pre-school years. Oxford University Press, OxfordGoogle Scholar
  113. Murray L, Halligan SL, Goodyer I, Herbert J (2010) Disturbances in early parenting of depressed mothers and cortisol secretion in offspring: a preliminary study. J Affect Disord 122(3):218–223CrossRefPubMedGoogle Scholar
  114. O’Hara MW, Zekoski EM, Philipps LH, Wright EJ (1990) Controlled prospective study of postpartum mood disorders: comparison of childbearing and non childbearing women. J Abnorm Psychol 99(1):3–15CrossRefPubMedGoogle Scholar
  115. Pessoa L, Adolphs R (2010) Emotion processing and the amygdala: from a ‘low road’ to ‘many roads’ of evaluating biological significance. Nat Rev Neurosci 11(11):773–783CrossRefPubMedGoogle Scholar
  116. Peterson BS, Warner V, Bansal R, Zhu H, Hao X, Liu J, Durkin K, Adams PB, Wickramaratne P, Weissman MM (2009) Cortical thinning in persons at increased familial risk for major depression. Proc Nat Acad Sci USA 106(15):6273–6278CrossRefPubMedGoogle Scholar
  117. Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR (2005) 5-HTTLPR polymorphism impacts human cingulate–amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 8(6):828–834CrossRefPubMedGoogle Scholar
  118. Pezawas L, Meyer-Lindenberg A, Goldman AL, Verchinski BA, Chen G, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR (2008) Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression. Mol Psychiatry 13(7):709–716CrossRefPubMedGoogle Scholar
  119. Pezawas L, Verchinski BA, Mattay VS, Callicott JH, Kolachana BS, Straub RE, Egan MF, Meyer-Lindenberg A, Weinberger DR (2004) The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci 24(45):10099–10102CrossRefPubMedGoogle Scholar
  120. Pizzagalli DA, Holmes AJ, Dillon DG, Goetz EL, Birk JL, Bogdan R, Dougherty DD, Iosifescu DV, Rauch SL, Fava M (2009) Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am J Psychiatry 166(6):702–710CrossRefPubMedGoogle Scholar
  121. Posener JA, Schildkraut JJ, Samson JA, Schatzberg AF (1996) Diurnal variation of plasma cortisol and homovanillic acid in healthy subjects. Psychoneuroendocrinology 21(1):33–38CrossRefPubMedGoogle Scholar
  122. Price JL, Drevets WC (2010) Neurocircuitry of mood disorders. Neuropsychopharmacology 35(1):192–216CrossRefPubMedGoogle Scholar
  123. Pruessner M, Hellhammer DH, Pruessner JC, Lupien SJ (2003) Self-reported depressive symptoms and stress levels in healthy young men: associations with the cortisol response to awakening. Psychosom Med 65(1):92–99CrossRefPubMedGoogle Scholar
  124. Radecki DT, Brown LM, Martinez J, Teyler TJ (2005) BDNF protects against stress-induced impairments in spatial learning and memory and LTP. Hippocampus 15(2):246–253CrossRefPubMedGoogle Scholar
  125. Rao U, Chen LA, Bidesi AS, Shad MU, Thomas MA, Hammen CL (2010) Hippocampal changes associated with early-life adversity and vulnerability to depression. Biol Psychiatry 67(4):357–364CrossRefPubMedGoogle Scholar
  126. Rao U, Hammen CL, Poland RE (2009) Risk markers for depression in adolescents: sleep and HPA measures. Neuropsychopharmacology 34(8):1936–1945CrossRefPubMedGoogle Scholar
  127. Ridderinkhoff KR, Ullsperger M, Crone EA, Nieuwenhuis S (2004) The role of the medial frontal cortex in cognitive control. Science 306(5695):443–447CrossRefGoogle Scholar
  128. Rice F, Harold GT, Thapar A (2003) Negative life events as an account of age-related differences in the genetic aetiology of depression in childhood and adolescence. J Child Psychol Psychiatry 44:977–987CrossRefPubMedGoogle Scholar
  129. Roceri M, Hendriks W, Racagni G, Ellenbroek BA, Riva MA (2002) Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus. Mol Psychiatry 7(6):609–616CrossRefPubMedGoogle Scholar
  130. Sanchez MM, Ladd CO, Plotsky PM (2001) Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models. Dev Psychopathol 13(3):419–449CrossRefPubMedGoogle Scholar
  131. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301(5634):805–809CrossRefPubMedGoogle Scholar
  132. Sapolsky RM (2000) The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry 48(8):755–765CrossRefPubMedGoogle Scholar
  133. Sapolsky RM, Krey LC, McEwen BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 7(3):284–301CrossRefPubMedGoogle Scholar
  134. Scharinger C, Rabl U, Sitte HH, Pezawas L (2010) Imaging genetics of mood disorders. Neuroimage 53(3):810–821CrossRefPubMedGoogle Scholar
  135. Schlotz W, Hellhammer J, Schulz P, Stone AA (2004) Perceived work overload and chronic worrying predict weekend-weekday differences in the cortisol awakening response. Psychosom Med 66(2):207–214CrossRefPubMedGoogle Scholar
  136. Schmahmann JD, Pandya DN, Wang R, Dai G, D’Arceuil HE, de Crespigny AJ, Wedeen VJ (2007) Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 130(3):630–653CrossRefPubMedGoogle Scholar
  137. Schumacher J, Jamra RA, Becker T, Ohlraun S, Klopp N, Binder EB, Schulze TG, Deschner M, Schmäl C, Höfels S, Zobel A, Illig T, Propping P, Holsboer F, Rietschel M, Nöthen MM, Cichon S (2005) Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. Biol Psychiatry 58(4):307–314CrossRefPubMedGoogle Scholar
  138. Selvaraj S, Godlewska BR, Norbury R, Bose S, Turkheimer F, Stokes P, Rhodes R, Howes O, Cowen PJ (2011) Decreased regional gray matter volume in S’ allele carriers of the 5-HTTLPR triallelic polymorphism. Mol Psychiatry 16(5):472–473CrossRefGoogle Scholar
  139. Sexton CE, Mackay CE, Ebmeier KP (2009) A systematic review of diffusion tensor imaging studies in affective disorders. Biol Psychiatry 66(9):814–823CrossRefPubMedGoogle Scholar
  140. Steele JD, Kumar P, Ebmeier KP (2007) Blunted response to feedback information in depressive illness. Brain 130(Pt 9):2367–2374CrossRefPubMedGoogle Scholar
  141. Steptoe A, Cropley M, Griffith J, Kirschbaum C (2000) Job strain and anger expression predict early morning elevations in salivary cortisol. Psychosom Med 62(2):286–292PubMedGoogle Scholar
  142. Stetler C, Miller GE (2005) Blunted cortisol response to awakening in mild to moderate depression: regulatory influences of sleep patterns and social contacts. J Abnorm Psychol 114(4):697–705CrossRefPubMedGoogle Scholar
  143. Stetler C, Miller GE (2011) Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom Med 73(2):114–126CrossRefPubMedGoogle Scholar
  144. Suomi SJ (1991) Early stress and adult emotional reactivity in rhesus monkeys. Ciba Found Symp 156(171–183):183–188Google Scholar
  145. Thapar A, Harold G, McGuffin P (1998) Life events and depressive symptoms in childhood-shared genes or shared adversity? A research note. J Child Psychol Psychiatry 39:1153–1158CrossRefPubMedGoogle Scholar
  146. Tottenham N, Hare TA, Quinn BT, McCarry TW, Nurse M, Gilhooly T, Millner A, Galvan A, Davidson MC, Eigsti IM, Thomas KM, Freed PJ, Booma ES, Gunnar MR, Altemus M, Aronson J, Casey BJ (2010) Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev Sci 13(1):46–61CrossRefPubMedGoogle Scholar
  147. van Harmelen AL, van Tol MJ, van der Wee NJ, Veltman DJ, Aleman A, Spinhoven P, van Buchem MA, Zitman FG, Penninx BW, Elzinga BM (2010) Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biol Psychiatry 68(9):832–838CrossRefPubMedGoogle Scholar
  148. Vermetten E, Vythilingam M, Southwick SM, Charney DS, Bremner JD (2003) Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder. Biol Psychiatry 54(7):693–702CrossRefPubMedGoogle Scholar
  149. Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 161(11):1957–1966CrossRefPubMedGoogle Scholar
  150. von dem Hagen EA, Passamonti L, Nutland S, Sambrook J, Calder AJ (2011) The serotonin transporter gene polymorphism and the effect of baseline on amygdala response to emotional faces. Neuropsychologia 49(4):674–680CrossRefGoogle Scholar
  151. Vreeburg SA, Hartman CA, Hoogendijk WJ, van Dyck R, Zitman FG, Ormel J, Penninx BW (2010) Parental history of depression or anxiety and the cortisol awakening response. Br J Psychiatry 197(3):180–185CrossRefPubMedGoogle Scholar
  152. Vreeburg SA, Hoogendijk WJ, van Pelt J, Derijk RH, Verhagen JC, van Dyck R, Smit JH, Zitman FG, Penninx BW (2009) Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry 66(6):617–626CrossRefPubMedGoogle Scholar
  153. 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(12):2072–2080CrossRefPubMedGoogle Scholar
  154. Way BM, Taylor SE (2010) The serotonin transporter promoter polymorphism is associated with cortisol response to psychosocial stress. Biol Psychiatry 67(5):487–492CrossRefPubMedGoogle Scholar
  155. Wichers M, Kenis G, Jacobs N, Mengelers R, Derom C, Vlietinck R, van Os J (2008) The BDNF Val(66)Met x 5-HTTLPR x child adversity interaction and depressive symptoms: an attempt at replication. Am J Med Genet 147B(1):120–123CrossRefPubMedGoogle Scholar
  156. Williamson DE, Birmaher B, Axelson DA, Ryan ND, Dahl RE (2004) First episode of depression in children at low and high familial risk for depression. J Am Acad Child Adolesc Psychiatry 43(3):291–297CrossRefPubMedGoogle Scholar
  157. Wust S, Federenko I, Hellhammer DH, Kirschbaum C (2000) Genetic factors, perceived chronic stress, and the free cortisol response to awakening. Psychoneuroendocrinology 25(7):707–720CrossRefPubMedGoogle Scholar
  158. Young EA, Aggen SH, Prescott CA, Kendler KS (2000) Similarity in saliva cortisol measures in monozygotic twins and the influence of past major depression. Biol Psychiatry 48(1):70–74CrossRefPubMedGoogle Scholar
  159. Young EA, Vazquez D, Jiang H, Pfeffer CR (2006) Saliva cortisol and response to dexamethasone in children of depressed parents. Biol Psychiatry 60(8):831–836CrossRefPubMedGoogle Scholar
  160. Zobel AW, Nickel T, Sonntag A, Uhr M, Holsboer F, Ising M (2001) Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression: a prospective study. J Psychiatr Res 35(2):83–94CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Lara C. Foland-Ross
    • 1
  • Michael G. Hardin
    • 1
  • Ian H. Gotlib
    • 1
    Email author
  1. 1.Department of PsychologyStanford UniversityStanfordUSA

Personalised recommendations