Adapting to Stress: Understanding the Neurobiology of Resilience

Behavioral Medicine

Volumn 43, Issue 4, 2017, Pages 307-322

  Osório, Carlos ^a   Probert, Thomas ^a   Jones, Edgar ^a   Young, Allan H ^a   Robbins, Ian ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

biological markers; depression; ; PTSD; resilience; uncontrollable stress

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; BREXANOLONE; CORTICOTROPIN RELEASING FACTOR; DOPAMINE; GALANIN; HYDROCORTISONE; NEUROPEPTIDE Y; NEUROTRANSMITTER; NORADRENALIN; PRASTERONE; PRASTERONE SULFATE; SEROTONIN;

ADRENERGIC SYSTEM; COMPREHENSION; DEVELOPMENT; DNA METHYLATION; DOPAMINERGIC SYSTEM; EPIGENETICS; HISTONE ACETYLATION; HISTONE METHYLATION; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; LIFE CYCLE; MAJOR DEPRESSION; MOLECULAR GENETICS; NEUROBIOLOGY; NEUROCHEMISTRY; NONHUMAN; NORADRENERGIC SYSTEM; POSTTRAUMATIC STRESS DISORDER; PSYCHOLOGICAL RESILIENCE; REVIEW; SEROTONINERGIC SYSTEM; SOCIAL ADAPTATION; BRAIN; COPING BEHAVIOR; MENTAL STRESS; METABOLISM; PHYSIOLOGY; PSYCHOLOGY; SYNAPTIC TRANSMISSION;

ADAPTATION, PSYCHOLOGICAL; BRAIN; HUMANS; RESILIENCE, PSYCHOLOGICAL; STRESS DISORDERS, POST-TRAUMATIC; STRESS, PSYCHOLOGICAL; SYNAPTIC TRANSMISSION;

EID: 85029773260     PISSN: 08964289     EISSN: 19404026     Source Type: Journal    
DOI: 10.1080/08964289.2016.1170661     Document Type: Review

References (168)

1. Selye H. The evolution of the stress concept: The originator of the concept traces its development from the discovery in 1936 of the alarm reaction to modern therapeutic applications of syntoxic and catatoxic hormones. Am Sci. 1973;61:692–699.
2. Selye H. Confusion and controversy in the stress field. J Human Stress. 1975;1:37–44.
3. Mason JW. A historical view of the stress field. J Human Stress. 1975;1:6–12.
4. McEwen BS. Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiol Rev. 2007;87:873–904.
5. McEwen BS, Stellar E. Stress and the individual: Mechanisms leading to disease. Arch Intern Med. 1993;153:2093–2101.
6. McEwen BS. The neurobiology of stress: From serendipity to clinical relevance. Brain Res. 2000;886:172–189.
7. Sterling P, Eyer J. Allostasis: A new paradigm to explain arousal pathology. In: Fisher S, Reason J, eds. Handbook of Life Stress, Cognition and Health. New York: John Willey and Sons; 1988:629–649.
8. Karatsoreos IN, McEwen BS. Psychobiological allostasis: Resistance, resilience and vulnerability. Trends Cogn Sci. 2011;15:576–584.
9. McEwen BS. Allostasis and allostatic load: Implications for neuropsychopharmacology. Neuropsychopharmacol. 2000;22:108–124.
10. Charney DS. Psychobiological mechanisms of resilience and vulnerability: Implications for successful adaptation to extreme stress. Am J Psych. 2004;161:195–216.
11. Feder A, Charney DS, Collins K. Pathways to resilience—Neurobiology of resilience. In: Southwick S, Litz BT, Charney DS, Friedman M, eds. Resilience and Mental Health: Challenges across the Lifespan. Cambridge, UK: Cambridge University Press; 2011:1–29.
12. Cannon WB. The Wisdom of the Body. Washington, DC: W. W. Norton & Company; 1963.
13. Charney DS. Neuroanatomical circuits modulating fear and anxiety behaviors. Acta Psychiatr Scand. 2003;108:38–50.
14. Heim C, Nemeroff CB. Neurobiology of posttraumatic stress disorder. CNS Spectrum. 2009;14:13–24.
15. Rasmusson AM, Vythilingam M, Morgan CA, 3rd. The neuroendocrinology of posttraumatic stress disorder: New directions. CNS Spectrum. 2003;8:651–656.
16. Russo SJ, Murrough JW, Han MH, Charney DS, Nestler EJ. Neurobiology of resilience. Nat Neurosci. 2012;15:1475–1484.
17. Feder A, Nestler EJ, Charney DS. Psychobiology and molecular genetics of resilience. Nat Rev Neurosci. 2009;10:446–457.
18. Wu G, Feder A, Cohen H, et al. Understanding resilience. Front Behav Neurosci. 2013;7:1–15.
19. Bonanno GA. Loss, trauma, and human resilience: Have we underestimated the human capacity to thrive after extremely aversive events? Psychol Trauma. 2008;1:101–113.
20. de Kloet ER. About stress hormones and resilience to psychopathology. J Neuroenocrinol. 2008;20:885–892.
21. Luthar SS, Cicchetti D, Becker B. The construct of resilience: A critical evaluation and guidelines for future work. Child Dev. 2000;71:543–562.
22. Luthar SS, Cicchetti D. The construct of resilience: Implications for interventions and social policies. Dev Psychopathol. 2000;12:857–885.
23. Southwick SM, Bonanno GA, Masten AS, Panter-Brick C, Yehuda R. Resilience definitions, theory, and challenges: Interdisciplinary perspectives. Eur J Psychotraumatol. 2014;5:1–14.
24. Bonanno GA. Uses and abuses of the resilience construct: Loss, trauma, and health-related adversities. Soc Sci Med. 2012;74:753–756.
25. Haglund ME, Nestadt PS, Cooper NS, Southwick SM, Charney DS. Psychobiological mechanisms of resilience: Relevance to prevention and treatment of stress-related psychopathology. Dev Psychopathol. 2007;19:889–920.
26. Jansen AS, Nguyen XV, Karpitskiy V, Mettenleiter TC, Loewy AD. Central command neurons of the sympathetic nervous system: Basis of the fight-or-flight response. Science. 1995;270:644–646.
27. Southwick SM, Bremner JD, Rasmusson AM, Morgan CA, 3rd, Arnsten A, Charney DS. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry. 1999;46:1192–1204.
28. Morgan CA, 3rd, Wang S, Mason J, et al. Hormone profiles in humans experiencing military survival training. Biol Psychiatry. 2000;47:891–901.
29. Morgan CA, 3rd, Wang S, Southwick SM, et al. Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biol Psychiatry. 2000;47:902–909.
30. Krystal JH, Neumeister A. Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Res. 2009;1293:13–23.
31. McGaugh JL. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu Rev Neurosci. 2004;27:1–28.
32. Heilig M, Widerlov E. Neurobiology and clinical aspects of neuropeptide Y. Crit Rev Neurobiol. 1995;9:115–136.
33. Corder R, Castagne V, Rivet JM, Mormede P, Gaillard RC. Central and peripheral effects of repeated stress and high NaCl diet on neuropeptide Y. Physiol Behav. 1992;52:205–210.
34. Morgan CA, 3rd, Rasmusson AM, Wang S, Hoyt G, Hauger RL, Hazlett GA. Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: Replication and extension of previous report. Biol Psychiatry. 2002;52:136–142.
35. Cohen H, Liu T, Kozlovsky N, Kaplan Z, Zohar J, Mathe AA. The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder. Neuropsychopharmacol. 2012;37:350–363.
36. Rasmusson AM, Hauger RL, Morgan CA, 3rd, Bremner JD, Charney DS, Southwick SM. Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD. Biol Psychiatry. 2000;47:526–539.
37. Sah R, Ekhator NN, Strawn JR, et al. Low cerebrospinal fluid neuropeptide Y concentrations in posttraumatic stress disorder. Biol Psychiatry. 2009;66:705–707.
38. Hou C, Jia F, Liu Y, Li L. CSF serotonin, 5-hydroxyindolacetic acid and neuropeptide Y levels in severe major depressive disorder. Brain Res. 2006;1095:154–158.
39. Sabban EL, Serova LI, Alaluf LG, Laukova M, Peddu C. Comparative effects of intranasal neuropeptide Y and HS014 in preventing anxiety and depressive-like behavior elicited by single prolonged stress. Behav Brain Res. 2015;295:9–16.
40. Murrough JW. A dose escalation study of intranasal neuropeptide Y in post-traumatic stress disorder (PTSD). https://clinicaltrials.gov/ct2/show/study/NCT01533519. Accessed December16, 2015.
41. Evans H, Baumgartner M, Shine J, Herzog H. Genomic organization and localization of the gene encoding human preprogalanin. Genomics. 1993;18:473–477.
42. Mechenthaler I. Galanin and the neuroendocrine axes. Cell Molec Life Sci. 2008;65:1826–1835.
43. Holmes A, Yang RJ, Crawley JN. Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice. J Molec Neurosci. 2002;18:151–165.
44. Ito M. Functional roles of neuropeptides in cerebellar circuits. Neuroscience. 2009;162:666–672.
45. Southwick SM, Morgan CA, 3rd, Vythilingam M, Krystal JH, Charney DS. Emerging neurobiological factors in stress resilience. PTSD Res Quart. 2003;14:1–8.
46. Sevcik J, Finta EP, Illes P. Galanin receptors inhibit the spontaneous firing of locus coeruleus neurones and interact with mu-opioid receptors. Eur J Pharmacol. 1993;230:223–230.
47. Bing O, Moller C, Engel JA, Soderpalm B, Heilig M. Anxiolytic-like action of centrally administered galanin. Neurosci Lett. 1993;164:17–20.
48. Moller C, Sommer W, Thorsell A, Heilig M. Anxiogenic-like action of galanin after intra-amygdala administration in the rat. Neuropsychopharmacol. 1999;21:507–512.
49. Sciolino NR, Smith JM, Stranahan AM, et al. Galanin mediates features of neural and behavioral stress resilience afforded by exercise. Neuropharmacol. 2015;89:255–264.
50. Herman JP, Cullinan WE. Neurocircuitry of stress: Central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci. 1997;20:78–84.
51. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53:865–871.
52. Jones T, Moller MD. Implications of hypothalamic-pituitary-adrenal axis functioning in posttraumatic stress disorder. J Am Psychiatr Nurses Assoc. 2011;17:393–403.
53. de Kloet ER, Joels M, Holsboer F. Stress and the brain: From adaptation to disease. Nat Rev Neurosci. 2005;6:463–475.
54. de Kloet ER, Derijk RH, Meijer OC. Therapy Insight: Is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression? Nat Clin Pract Endocrinol Metab. 2007;3:168–179.
55. Claes SJ. Corticotropin-releasing hormone (CRH) in psychiatry: From stress to psychopathology. Ann Med. 2004;36:50–61.
56. Southwick SM, Vythilingam M, Charney DS. The psychobiology of depression and resilience to stress: Implications for prevention and treatment. Ann Rev Clin Psychol. 2005;1:255–291.
57. Bremner JD, Licinio J, Darnell A, et al. Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. Am J Psych. 1997;154:624–629.
58. Baker DG, West SA, Nicholson WE, et al. Serial CSF corticotropin-releasing hormone levels and adrenocortical activity in combat veterans with posttraumatic stress disorder. Am J Psych. 1999;156:585–588.
59. Nemeroff CB. Recent advances in the neurobiology of depression. Psychopharmacol Bull. 2002;36:6–23.
60. Holsboer F, Ising M. Stress hormone regulation: Biological role and translation into therapy. Ann Rev Psychol. 2010;61:81–109.
61. Paez-Pereda M, Hausch F, Holsboer F. Corticotropin releasing factor receptor antagonists for major depressive disorder. Expert Opin Investig Drugs. 2011;20:519–535.
62. Binder EB, Nemeroff CB. The CRF system, stress, depression and anxiety-insights from human genetic studies. Mol Psychiatry. 2010;15:574–588.
63. Hauger RL, Risbrough V, Oakley RH, Olivares-Reyes JA, Dautzenberg FM. Role of CRF receptor signaling in stress vulnerability, anxiety, and depression. Ann N Y Acad Sci. 2009;1179:120–143.
64. Bale TL, Contarino A, Smith GW, et al. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet. 2000;24:410–414.
65. Bale TL, Picetti R, Contarino A, Koob GF, Vale WW, Lee KF. Mice deficient for both corticotropin-releasing factor receptor 1 (CRFR1) and CRFR2 have an impaired stress response and display sexually dichotomous anxiety-like behavior. J Neurosci. 2002;22:193–199.
66. Coste SC, Kesterson RA, Heldwein KA, et al. Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nat Genet. 2000;24:403–409.
67. Gold PW, Drevets WC, Charney DS. New insights into the role of cortisol and the glucocorticoid receptor in severe depression. Biol Psychiatry. 2002;52:381–385.
68. Fiorentino L, Saxbe D, Alessi CA, Woods DL, Martin JL. Diurnal cortisol and functional outcomes in post-acute rehabilitation patients. J Gerontol. 2012;67:677–682.
69. Newcomer JW, Selke G, Melson AK, et al. Decreased memory performance in healthy humans induced by stress-level cortisol treatment. Arch Gen Psychiatry. 1999;56:527–533.
70. Southwick SM, Axelrod SR, Wang S, et al. Twenty-four-hour urine cortisol in combat veterans with PTSD and comorbid borderline personality disorder. J Nerv Ment Dis. 2003;191:261–262.
71. Morgan CA, 3rd, Southwick SM, Hazlett GA, et al. Relationships among plasma dehydroepiandrosterone sulfate and cortisol levels, symptoms of dissociation, and objective performance in humans exposed to acute stress. Arch Gen Psychiatry. 2004;61:819–825.
72. Morgan CA, 3rd, Rasmusson AM, Pietrzak RH, Coric V, Southwick SM. Relationships among plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate, cortisol, symptoms of dissociation, and objective performance in humans exposed to underwater navigation stress. Biol Psychiatry. 2009;66:334–340.
73. Taylor MK. Dehydroepiandrosterone and dehydroepiandrosterone sulfate: Anabolic, neuroprotective, and neuroexcitatory properties in military men. Mil Med. 2013;178:100–106.
74. Taylor MK, Padilla GA, Stanfill KE, et al. Effects of dehydroepiandrosterone supplementation during stressful military training: A randomized, controlled, double-blind field study. Stress. 2012;15:85–96.
75. van Niekerk JK, Huppert FA, Herbert J. Salivary cortisol and DHEA: Association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation. Psychoneuroendocrinol. 2001;26:591–612.
76. Barnhart KT, Freeman E, Grisso JA, et al. The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life. J Clin Endocrinol Metabol. 1999;84:3896–3902.
77. Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: A double-blind, placebo-controlled study. Psychopharmacol. 2006;188:541–551.
78. Sondergaard HP, Hansson LO, Theorell T. Elevated blood levels of dehydroepiandrosterone sulphate vary with symptom load in posttraumatic stress disorder: findings from a longitudinal study of refugees in Sweden. Psychother Psychosom. 2002;71:298–303.
79. Yehuda R, Brand SR, Golier JA, Yang RK. Clinical correlates of DHEA associated with post-traumatic stress disorder. Acta Psychiatr Scand.2006;114:187–193.
80. Pani L, Porcella A, Gessa GL. The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry. 2000;5:14–21.
81. Morrow BA, Elsworth JD, Rasmusson AM, Roth RH. The role of mesoprefrontal dopamine neurons in the acquisition and expression of conditioned fear in the rat. Neurosci. 1999;92:553–564.
82. Harvey BH, Naciti C, Brand L, Stein DJ. Serotonin and stress: Protective or malevolent actions in the biobehavioral response to repeated trauma? Ann N Y Acad Sci. 2004;1032:267–272.
83. Akimova E, Lanzenberger R, Kasper S. The serotonin-1A receptor in anxiety disorders. Biol Psychiatry 2009;66:627–635.
84. Benekareddy M, Vadodaria KC, Nair AR, Vaidya VA. Postnatal serotonin type 2 receptor blockade prevents the emergence of anxiety behavior, dysregulated stress-induced immediate early gene responses, and specific transcriptional changes that arise following early life stress. Biol Psychiatry. 2011;70:1024–1032.
85. Jones KR, Reichardt LF. Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc Nat Acad Sci. 1990;87:8060–8064.
86. Maisonpierre PC, Le Beau MM, Espinosa R, 3rd, et al. Human and rat brain-derived neurotrophic factor and neurotrophin-3: Gene structures, distributions, and chromosomal localizations. Genomics 1991;10:558–568.
87. Acheson A, Conover JC, Fandl JP, et al. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature. 1995;374:450–453.
88. Huang EJ, Reichardt LF. Neurotrophins: Roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.
89. Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59:1116–1127.
90. Duman RS. Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: Stress and depression. Dialogues Clin Neurosci. 2009;11:239–255.
91. Mahan AL, Ressler KJ. Fear conditioning, synaptic plasticity and the amygdala: Implications for posttraumatic stress disorder. Trends Neurosci. 2012;35:24–35.
92. Masi G, Brovedani P. The hippocampus, neurotrophic factors and depression: Possible implications for the pharmacotherapy of depression. CNS Drugs. 2011;25:913–931.
93. Bali A, Jaggi AS. Multifunctional aspects of allopregnanolone in stress and related disorders. Prog Neuropsychopharmacol Bio Psych. 2014;48:64–78.
94. Melcangi RC, Panzica GC. Allopregnanolone: State of the art. Prog Neurobiol. 2014;113:1–5.
95. Evans J, Sun Y, McGregor A, Connor B. Allopregnanolone regulates neurogenesis and depressive/anxiety-like behaviour in a social isolation rodent model of chronic stress. Neuropharmacol. 2012;63:1315–1326.
96. Girdler SS, Klatzkin R. Neurosteroids in the context of stress: Implications for depressive disorders. Pharmacol Therapeut. 2007;116:125–139.
97. Purdy RH, Morrow AL, Moore PH, Jr., Paul SM. Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain. Proc Nat Acad Sci. 1991;88:4553–4557.
98. Schule C, Nothdurfter C, Rupprecht R. The role of allopregnanolone in depression and anxiety. Prog Neurobiol. 2014;113:79–87.
99. Vogel F, Motulsky AG. Human Genetics: Problems and Approaches. New York: Springer; 1997.
100. Southwick SM, Charney DS. The science of resilience: Implications for the prevention and treatment of depression. Science. 2012;338:79–82.
101. Lukey BJ, Tepe V. Biobehavioral Resilience to Stress. London: Taylor and Francis; 2008.
102. Finley JC, Jr., O'Leary M, Wester D, et al. A genetic polymorphism of the alpha2-adrenergic receptor increases autonomic responses to stress. J Appl Physiol. 2004;96:2231–2239.
103. Kallio J, Pesonen U, Kaipio K, et al. Altered intracellular processing and release of neuropeptide Y due to leucine 7 to proline 7 polymorphism in the signal peptide of preproneuropeptide Y in humans. FASEB Journal. 2001;15:1242–1244.
104. Jimenez-Rivera CA, Segarra O, Santacana G, Hoffman T, Savage DD, Weiss GK. Chronic imipramine treatment induces downregulation of alpha-2 receptors in rat's locus coeruleus and A2 region of the tractus solitarius. Life Sciences. 1996;58:287–294.
105. Donner J, Sipila T, Ripatti S, et al. Support for involvement of glutamate decarboxylase 1 and neuropeptide Y in anxiety susceptibility. Am J Med Genet. 2012;159b:316–327.
106. Zhou Z, Zhu G, Hariri AR, et al. Genetic variation in human NPY expression affects stress response and emotion. Nature. 2008;452:997–1001.
107. Domschke K, Dannlowski U, Hohoff C, et al. Neuropeptide Y (NPY) gene: Impact on emotional processing and treatment response in anxious depression. Eur Neuropsychopharmacol. 2010;20:301–309.
108. Gillespie CF, Phifer J, Bradley B, Ressler KJ. Risk and resilience: Genetic and environmental influences on development of the stress response. Depress Anxiety. 2009;26:984–992.
109. Heim C, Bradley B, Mletzko TC, et al. Effect of childhood trauma on adult depression and neuroendocrine function: Sex-specific moderation by CRH receptor 1 gene. Front Behav Neurosci. 2009;41:1–10.
110. Polanczyk G, Caspi A, Williams B, et al. Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: Replication and extension. Arch Gen Psychiatry. 2009;66:978–985.
111. Binder EB, Bradley RG, Liu W, et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008;299:1291–1305.
112. Zimmermann P, Bruckl T, Nocon A, et al. Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: Results from a 10-year prospective community study. Am J Psych. 2011;168:1107–1116.
113. Heinz A, Smolka MN. The effects of catechol O-methyltransferase genotype on brain activation elicited by affective stimuli and cognitive tasks. Rev Neurosci. 2006;17:359–367.
114. Kolassa IT, Kolassa S, Ertl V, Papassotiropoulos A, De Quervain DJ. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biol Psychiatry. 2010;67:304–308.
115. Schulz-Heik RJ, Schaer M, Eliez S, et al. Catechol-O-methyltransferase Val158Met polymorphism moderates anterior cingulate volume in posttraumatic stress disorder. Biol Psychiatry. 2011;70:1091–1096.
116. Segman RH, Cooper-Kazaz R, Macciardi F, et al. Association between the dopamine transporter gene and posttraumatic stress disorder. Mol Psychiatry. 2002;7:903–907.
117. Blasi G, Lo Bianco L, Taurisano P, et al. Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans. J Neurosci. 2009;29:14812–14819.
118. Ptácek R, Kuzelova H, Stefano GB. Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders. Medical Sci Monitor. 2011;17:215–220.
119. Karg K, Burmeister M, Shedden K, Sen S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Arch Gen Psychiatry. 2011;68:444–454.
120. Xie P, Kranzler HR, Poling J, et al. Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Arch Gen Psychiatry. 2009;66:1201–1209.
121. Stein MB, Campbell-Sills L, Gelernter J. Genetic variation in 5HTTLPR is associated with emotional resilience. Am J Med Genet. 2009;150:900–906.
122. Alexander N, Osinsky R, Schmitz A, Mueller E, Kuepper Y, Hennig J. The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress. Psychoneuroendocrinol. 2010;35:949–953.
123. Colzato LS, Van der Does AJ, Kouwenhoven C, Elzinga BM, Hommel B. BDNF Val66Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults. Psychoneuroendocrinol. 2011;36:1562–1569.
124. Lee Y, Lim SW, Kim SY, et al. Association between the BDNF Val66Met polymorphism and chronicity of depression. Psychiatry Investig. 2013;10:56–61.
125. Gatt JM, Nemeroff CB, Dobson-Stone C, et al. Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molec Psych. 2009;14:681–695.
126. Verhagen M, van der Meij A, van Deurzen PA, et al. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: Effects of gender and ethnicity. Molec Psych. 2010;15:260–271.
127. Wang T. Does BDNF Val66Met polymorphism confer risk for posttraumatic stress disorder? Neuropsychobiol. 2015;71:149–153.
128. Frustaci A, Pozzi G, Gianfagna F, Manzoli L, Boccia S. Meta-analysis of the brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism in anxiety disorders and anxiety-related personality traits. Neuropsychobiol. 2008;58:163–170.
129. Dudley KJ, Li X, Kobor MS, Kippin TE, Bredy TW. Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders. Neurosci Biobehav Rev. 2011;35:1544–1551.
130. Vialou V, Feng J, Robison AJ, Nestler EJ. Epigenetic mechanisms of depression and antidepressant action. Annu Rev Pharmacol Toxicol. 2013;53:59–87.
131. Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proceed Nat Acad Sci. 2005;102:10604–10609.
132. Sun H, Kennedy PJ, Nestler EJ. Epigenetics of the depressed brain: Role of histone acetylation and methylation. Neuropsychopharmacol. 2013;38:124–137.
133. McGowan PO, Sasaki A, D'Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12:342–348.
134. Poulter MO, Du L, Weaver IC, et al. GABAA receptor promoter hypermethylation in suicide brain: Implications for the involvement of epigenetic processes. Biol Psychiatry. 2008;64:645–652.
135. Uddin M, Galea S, Chang SC, et al. Gene expression and methylation signatures of MAN2C1 are associated with PTSD. Dis Markers. 2011;30:111–121.
136. Koenen KC, Guffanti G, Yan L, et al. Genetics of PTSD. In: Friedman MJ, Keane TM, Resick PA, eds. Handbook of PTSD: Science and Practice. New York: The Guildford Press; 2014:300–312.
137. Kramer JM. Epigenetic regulation of memory: Implications in human cognitive disorders. Biomol Concepts. 2013;4:1–12.
138. Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ. Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proceed Nat Acad Sci. 1998;95:5335–5340.
139. Weaver IC, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7:847–854.
140. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997;389:349–352.
141. Covington HE, 3rd, Maze I, LaPlant QC, et al. Antidepressant actions of histone deacetylase inhibitors. J Neurosci. 2009;29:11451–11460.
142. Bagot RC, Labonte B, Pena CJ, Nestler EJ. Epigenetic signaling in psychiatric disorders: Stress and depression. Dialogues Clin Neurosci. 2014;16:281–295.
143. Renthal W, Maze I, Krishnan V, et al. Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron. 2007;56:517–529.
144. Rende R. Behavioral resilience in the post-genomic era: Emerging models linking genes with environment. Front Hum Neurosci. 2012;650:1–5.
145. Kaufman J, Plotsky PM, Nemeroff CB, Charney DS. Effects of early adverse experiences on brain structure and function: Clinical implications. Biol Psychiatry. 2000;48:778–790.
146. Heim C, Newport DJ, Mletzko T, Miller AH, Nemeroff CB. The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinol. 2008;33:693–710.
147. Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies. Biol Psychiatry. 2001;49:1023–1039.
148. Shonkoff JP, Garner AS. The lifelong effects of early childhood adversity and toxic stress. Pediatrics. 2012;129:232–246.
149. Dannlowski U, Stuhrmann A, Beutelmann V, et al. Limbic scars: Long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biol Psychiatry.2012;71:286–293.
150. Davidson RJ, McEwen BS. Social influences on neuroplasticity: Stress and interventions to promote well-being. Nat Neurosci. 2012;15:689–695.
151. Overmier JB, Seligman ME. Effects of inescapable shock upon subsequent escape and avoidance responding. J Comp Physiol Psychol. 1967;63:28–33.
152. Nolen JL. “Learned helplessness.” Encyclopaedia Britannica. http://www.britannica.com/topic/learned-helplessness. Accessed June15, 2015.
153. Seligman ME, Maier SF. Failure to escape traumatic shock. J Exp Psychol 1967;74:1–9.
154. West LJ. Psychiatric aspects of training for honorable survival as a prisoner of war. Am J Psych. 1958;115:329–336.
155. Doran AP, Hoyt G, Morgan CA, 3rd. Survival, evasion, resistance and escape (SERE) training: Preparing military members for the demands of captivity. In: Kennedy CH, Zillmer EA, eds. Military Psychology—Clinical and Operational Applications. New York: The Guilford Press; 2006:241–261.
156. Meichenbaum D. Stress Inoculation Training. New York: Pergamon Press; 1985.
157. Levine S. Plasma-free corticosteroid response to electric shock in rats stimulated in infancy. Science 1962;135:795–796.
158. Lyons DM, Parker KJ, Schatzberg AF. Animal models of early life stress: Implications for understanding resilience. Dev Psychobiol. 2010;52:402–410.
159. Ozbay F, Fitterling H, Charney D, Southwick S. Social support and resilience to stress across the life span: A neurobiologic framework. Curr Psychiatry Rep. 2008;10:304–310.
160. Arnberg FK, Hultman CM, Michel PO, Lundin T. Social support moderates posttraumatic stress and general distress after disaster. J Trauma Stress. 2012;25:721–727.
161. Ozbay F, Johnson DC, Dimoulas E, Morgan CA, 3rd, Charney DS, Southwick SM. Social support and resilience to stress: From neurobiology to clinical practice. Psychiatry. 2007;4:35–40.
162. Bowes L, Jaffee SR. Biology, genes, and resilience: Toward a multidisciplinary approach. Trauma, Violence Abuse. 2013;14:195–208.
163. Simmons AN, Fitzpatrick S, Strigo IA, et al. Altered insula activation in anticipation of changing emotional states: Neural mechanisms underlying cognitive flexibility in Special Operations Forces personnel. Cog Neurosci Neuropsychol. 2012;1–6.
164. Taverniers J, Taylor MK, Smeets T. Delayed memory effects after intense stress in Special Forces candidates: Exploring path processes between cortisol secretion and memory recall. Stress. 2012; 16:311–320.
165. Taverniers J, Van Ruysseveldt J, Smeets T, von Grumbkow J. High-intensity stress elicits robust cortisol increases, and impairs working memory and visuo-spatial declarative memory in Special Forces candidates: A field experiment. Stress. 2010;13:323–333.
166. Vythilingam M, Nelson EE, Scaramozza M, et al. Reward circuitry in resilience to severe trauma: An fMRI investigation of resilient special forces soldiers. Psychiatry Res. 2009;172:75–77.
167. Burki TK. Profile: KCMHR—Dispelling myths about military health. Lancet. 2012;380:1136.
168. Tracey I, Flower R. The warrior in the machine: Neuroscience goes to war. Nat Rev Neurosci. 2014;15:825–834.