Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Neurobiology of resilience

Abstract

Humans exhibit a remarkable degree of resilience in the face of extreme stress, with most resisting the development of neuropsychiatric disorders. Over the past 5 years, there has been increasing interest in the active, adaptive coping mechanisms of resilience; however, in humans, most published work focuses on correlative neuroendocrine markers that are associated with a resilient phenotype. In this review, we highlight a growing literature in rodents that is starting to complement the human work by identifying the active behavioral, neural, molecular and hormonal basis of resilience. The therapeutic implications of these findings are important and can pave the way for an innovative approach to drug development for a range of stress-related syndromes.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Schematic of gene × environment interactions that promote resilience.
Figure 2: Stress inoculation shifts the inverted U-shaped curve to promote resilience.
Figure 3: Brain circuitry implicated in resilience to depression and anxiety disorders.
Figure 4: Active molecular mechanisms in limbic brain circuits that promote resilience in animal models.

References

  1. 1

    Charney, D.S. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am. J. Psychiatry 161, 195–216 (2004).

    PubMed  Google Scholar 

  2. 2

    Feder, A., Nestler, E.J. & Charney, D.S. Psychobiology and molecular genetics of resilience. Nat. Rev. Neurosci. 10, 446–457 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Herman, J.P. & Cullinan, W.E. Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci. 20, 78–84 (1997).

    CAS  PubMed  Google Scholar 

  4. 4

    Stetler, C. & Miller, G.E. Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom. Med. 73, 114–126 (2011).

    PubMed  Google Scholar 

  5. 5

    Meewisse, M.L., Reitsma, J.B., de Vries, G.J., Gersons, B.P. & Olff, M. Cortisol and post-traumatic stress disorder in adults: systematic review and meta-analysis. Br. J. Psychiatry 191, 387–392 (2007).

    PubMed  Google Scholar 

  6. 6

    Heim, C., Newport, D.J., Mletzko, T., Miller, A.H. & Nemeroff, C.B. The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 33, 693–710 (2008).

    CAS  PubMed  Google Scholar 

  7. 7

    Heim, C., Newport, D.J., Miller, A.H. & Nemeroff, C.B. Long-term neuroendocrine effects of childhood maltreatment. J. Am. Med. Assoc. 284, 2321 (2000).

    CAS  Google Scholar 

  8. 8

    Yehuda, R., Golier, J.A. & Kaufman, S. Circadian rhythm of salivary cortisol in Holocaust survivors with and without PTSD. Am. J. Psychiatry 162, 998–1000 (2005).

    PubMed  Google Scholar 

  9. 9

    Rasmusson, A.M., Vythilingam, M. & Morgan, C.A. III. The neuroendocrinology of posttraumatic stress disorder: new directions. CNS Spectr. 8, 651–656, 665–667 (2003).

    PubMed  Google Scholar 

  10. 10

    Yehuda, R., Brand, S.R., Golier, J.A. & Yang, R.K. Clinical correlates of DHEA associated with post-traumatic stress disorder. Acta Psychiatr. Scand. 114, 187–193 (2006).

    CAS  PubMed  Google Scholar 

  11. 11

    Butterfield, M.I. et al. Neuroactive steroids and suicidality in posttraumatic stress disorder. Am. J. Psychiatry 162, 380–382 (2005).

    PubMed  Google Scholar 

  12. 12

    Taylor, M.K. et al. Effects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field study. Stress 15, 85–96 (2012).

    CAS  PubMed  Google Scholar 

  13. 13

    Oliveira, T., Gouveia, M.J. & Oliveira, R.F. Testosterone responsiveness to winning and losing experiences in female soccer players. Psychoneuroendocrinology 34, 1056–1064 (2009).

    CAS  PubMed  Google Scholar 

  14. 14

    Edwards, D.A., Wetzel, K. & Wyner, D.R. Intercollegiate soccer: saliva cortisol and testosterone are elevated during competition, and testosterone is related to status and social connectedness with team mates. Physiol. Behav. 87, 135–143 (2006).

    CAS  PubMed  Google Scholar 

  15. 15

    Morgan, C.A. III et al. Hormone profiles in humans experiencing military survival training. Biol. Psychiatry 47, 891–901 (2000).

    CAS  PubMed  Google Scholar 

  16. 16

    Mulchahey, J.J. et al. Cerebrospinal fluid and plasma testosterone levels in post-traumatic stress disorder and tobacco dependence. Psychoneuroendocrinology 26, 273–285 (2001).

    CAS  PubMed  Google Scholar 

  17. 17

    Pope, H.G. Jr., Cohane, G.H., Kanayama, G., Siegel, A.J. & Hudson, J.I. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am. J. Psychiatry 160, 105–111 (2003).

    PubMed  Google Scholar 

  18. 18

    Morgan, C.A. III et al. Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biol. Psychiatry 47, 902–909 (2000).

    CAS  PubMed  Google Scholar 

  19. 19

    Morgan, C.A. III et al. Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report. Biol. Psychiatry 52, 136–142 (2002).

    CAS  PubMed  Google Scholar 

  20. 20

    Zhou, Z. et al. Genetic variation in human NPY expression affects stress response and emotion. Nature 452, 997–1001 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Mickey, B.J. et al. Emotion processing, major depression, and functional genetic variation of neuropeptide Y. Arch. Gen. Psychiatry 68, 158–166 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Taliaz, D. et al. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor. J. Neurosci. 31, 4475–4483 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Cohen, H. et al. The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder. Neuropsychopharmacology 37, 350–363 (2012).

    CAS  PubMed  Google Scholar 

  24. 24

    Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007).

    CAS  PubMed  Google Scholar 

  25. 25

    Lehmann, M.L. & Herkenham, M. Environmental enrichment confers stress resiliency to social defeat through an infralimbic cortex-dependent neuroanatomical pathway. J. Neurosci. 31, 6159–6173 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Delgado y Palacios, R. et al. Magnetic resonance imaging and spectroscopy reveal differential hippocampal changes in anhedonic and resilient subtypes of the chronic mild stress rat model. Biol. Psychiatry 70, 449–457 (2011).

    PubMed  Google Scholar 

  27. 27

    Golden, S.A., Covington, H.E. III, Berton, O. & Russo, S.J. A standardized protocol for repeated social defeat stress in mice. Nat. Protoc. 6, 1183–1191 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Lutter, M. et al. The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat. Neurosci. 11, 752–753 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Berton, O. et al. Induction of deltaFosB in the periaqueductal gray by stress promotes active coping responses. Neuron 55, 289–300 (2007).

    CAS  PubMed  Google Scholar 

  30. 30

    Fleshner, M., Maier, S.F., Lyons, D.M. & Raskind, M.A. The neurobiology of the stress-resistant brain. Stress 14, 498–502 (2011).

    PubMed  PubMed Central  Google Scholar 

  31. 31

    Vidal, J., Buwalda, B. & Koolhaas, J.M. Male Wistar rats are more susceptible to lasting social anxiety than wild-type Groningen rats following social defeat stress during adolescence. Behav. Processes 88, 76–80 (2011).

    PubMed  Google Scholar 

  32. 32

    Uchida, S. et al. Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events. Neuron 69, 359–372 (2011).

    CAS  PubMed  Google Scholar 

  33. 33

    Mozhui, K. et al. Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability. J. Neurosci. 30, 5357–5367 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Andrus, B.M. et al. Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models. Mol. Psychiatry 17, 49–61 (2012).

    CAS  PubMed  Google Scholar 

  35. 35

    Nesse, R.M. Is depression an adaptation? Arch. Gen. Psychiatry 57, 14–20 (2000).

    CAS  PubMed  Google Scholar 

  36. 36

    Berton, O. et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311, 864–868 (2006).

    CAS  PubMed  Google Scholar 

  37. 37

    Covington, H.E. III et al. Antidepressant actions of histone deacetylase inhibitors. J. Neurosci. 29, 11451–11460 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    Covington, H.E. III, Vialou, V.F., LaPlant, Q., Ohnishi, Y.N. & Nestler, E.J. Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci. Lett. 493, 122–126 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Masten, A.S. Ordinary magic. Resilience processes in development. Am. Psychol. 56, 227–238 (2001).

    CAS  PubMed  Google Scholar 

  40. 40

    Bonanno, G.A. Loss, trauma, and human resilience: have we underestimated the human capacity to thrive after extremely aversive events? Am. Psychol. 59, 20–28 (2004).

    PubMed  Google Scholar 

  41. 41

    Kessler, R.C., Sonnega, A., Bromet, E., Hughes, M. & Nelson, C.B. Posttraumatic stress disorder in the National Comorbidity Survey. Arch. Gen. Psychiatry 52, 1048–1060 (1995).

    CAS  PubMed  Google Scholar 

  42. 42

    Levine, S. Plasma-free corticosteroid response to electric shock in rats stimulated in infancy. Science 135, 795–796 (1962).

    CAS  PubMed  Google Scholar 

  43. 43

    Lyons, D.M., Parker, K.J. & Schatzberg, A.F. Animal models of early life stress: implications for understanding resilience. Dev. Psychobiol. 52, 616–624 (2010).

    PubMed  PubMed Central  Google Scholar 

  44. 44

    Parker, K.J., Buckmaster, C.L., Schatzberg, A.F. & Lyons, D.M. Prospective investigation of stress inoculation in young monkeys. Arch. Gen. Psychiatry 61, 933–941 (2004).

    PubMed  Google Scholar 

  45. 45

    Parker, K.J., Buckmaster, C.L., Justus, K.R., Schatzberg, A.F. & Lyons, D.M. Mild early life stress enhances prefrontal-dependent response inhibition in monkeys. Biol. Psychiatry 57, 848–855 (2005).

    PubMed  Google Scholar 

  46. 46

    Ricon, T., Toth, E., Leshem, M., Braun, K. & Richter-Levin, G. Unpredictable chronic stress in juvenile or adult rats has opposite effects, respectively, promoting and impairing resilience. Stress 15, 11–20 (2012).

    CAS  PubMed  Google Scholar 

  47. 47

    Bradley, R.G. et al. Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene. Arch. Gen. Psychiatry 65, 190–200 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Caspi, A., Hariri, A.R., Holmes, A., Uher, R. & Moffitt, T.E. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am. J. Psychiatry 167, 509–527 (2010).

    PubMed  PubMed Central  Google Scholar 

  49. 49

    Wallace, D.L. et al. CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. Nat. Neurosci. 12, 200–209 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    McEwen, B.S. & Gianaros, P.J. Stress- and allostasis-induced brain plasticity. Annu. Rev. Med. 62, 431–445 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Luine, V. Sex differences in chronic stress effects on memory in rats. Stress 5, 205–216 (2002).

    CAS  PubMed  Google Scholar 

  52. 52

    Christoffel, D.J. et al. IkappaB kinase regulates social defeat stress-induced synaptic and behavioral plasticity. J. Neurosci. 31, 314–321 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Tsankova, N.M. et al. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat. Neurosci. 9, 519–525 (2006).

    CAS  PubMed  Google Scholar 

  54. 54

    Christoffel, D.J. et al. Effects of inhibitor of κB kinase activity in the nucleus accumbens on emotional behavior. Neuropsychopharmacology published online, doi:10.1038/npp.2012.121 (11 July 2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Wood, S.K., Walker, H.E., Valentino, R.J. & Bhatnagar, S. Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor. Endocrinology 151, 1795–1805 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Ono, Y. et al. Active coping with stress suppresses glucose metabolism in the rat hypothalamus. Stress 15, 207–217 (2012).

    CAS  PubMed  Google Scholar 

  57. 57

    Wilkinson, M.B. et al. Imipramine treatment and resiliency exhibit similar chromatin regulation in the mouse nucleus accumbens in depression models. J. Neurosci. 29, 7820–7832 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Price, J.L. & Drevets, W.C. Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192–216 (2010).

    PubMed  Google Scholar 

  59. 59

    Murrough, J.W., Iacoviello, B., Neumeister, A., Charney, D.S. & Iosifescu, D.V. Cognitive dysfunction in depression: neurocircuitry and new therapeutic strategies. Neurobiol. Learn. Mem. 96, 553–563 (2011).

    CAS  PubMed  Google Scholar 

  60. 60

    Mayberg, H.S. Targeted electrode-based modulation of neural circuits for depression. J. Clin. Invest. 119, 717–725 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    van Tol, M.J. et al. Functional magnetic resonance imaging correlates of emotional word encoding and recognition in depression and anxiety disorders. Biol. Psychiatry 71, 593–602 (2012).

    PubMed  Google Scholar 

  62. 62

    Linden, D.E. How psychotherapy changes the brain–the contribution of functional neuroimaging. Mol. Psychiatry 11, 528–538 (2006).

    CAS  PubMed  Google Scholar 

  63. 63

    Christoffel, D.J., Golden, S.A. & Russo, S.J. Structural and synaptic plasticity in stress-related disorders. Rev. Neurosci. 22, 535–549 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Adamec, R., Toth, M., Haller, J., Halasz, J. & Blundell, J. A comparison of activation patterns of cells in selected prefrontal cortical and amygdala areas of rats which are more or less anxious in response to predator exposure or submersion stress. Physiol. Behav. 105, 628–638 (2012).

    CAS  PubMed  Google Scholar 

  65. 65

    Covington, H.E. III et al. Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J. Neurosci. 30, 16082–16090 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Katz, M. et al. Prefrontal plasticity and stress inoculation-induced resilience. Dev. Neurosci. 31, 293–299 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Milad, M.R., Orr, S.P., Pitman, R.K. & Rauch, S.L. Context modulation of memory for fear extinction in humans. Psychophysiology 42, 456–464 (2005).

    PubMed  Google Scholar 

  68. 68

    Rauch, S.L. et al. Orbitofrontal thickness, retention of fear extinction, and extraversion. Neuroreport 16, 1909–1912 (2005).

    PubMed  Google Scholar 

  69. 69

    Kozorovitskiy, Y. et al. Experience induces structural and biochemical changes in the adult primate brain. Proc. Natl. Acad. Sci. USA 102, 17478–17482 (2005).

    CAS  PubMed  Google Scholar 

  70. 70

    Lupien, S.J., McEwen, B.S., Gunnar, M.R. & Heim, C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci. 10, 434–445 (2009).

    CAS  PubMed  Google Scholar 

  71. 71

    Vialou, V. et al. DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nat. Neurosci. 13, 745–752 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Vialou, V. et al. Serum response factor promotes resilience to chronic social stress through the induction of DeltaFosB. J. Neurosci. 30, 14585–14592 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Cao, J.L. et al. Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action. J. Neurosci. 30, 16453–16458 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Goto, Y., Otani, S. & Grace, A.A. The Yin and Yang of dopamine release: a new perspective. Neuropharmacology 53, 583–587 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Grace, A.A., Floresco, S.B., Goto, Y. & Lodge, D.J. Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci. 30, 220–227 (2007).

    CAS  PubMed  Google Scholar 

  76. 76

    Brischoux, F., Chakraborty, S., Brierley, D.I. & Ungless, M.A. Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc. Natl. Acad. Sci. USA 106, 4894–4899 (2009).

    CAS  PubMed  Google Scholar 

  77. 77

    Lammel, S., Ion, D.I., Roeper, J. & Malenka, R.C. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron 70, 855–862 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Shumake, J., Ilango, A., Scheich, H., Wetzel, W. & Ohl, F.W. Differential neuromodulation of acquisition and retrieval of avoidance learning by the lateral habenula and ventral tegmental area. J. Neurosci. 30, 5876–5883 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Lüscher, C. & Slesinger, P.A. Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat. Rev. Neurosci. 11, 301–315 (2010).

    PubMed  PubMed Central  Google Scholar 

  80. 80

    Balana, B. et al. Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27. Proc. Natl. Acad. Sci. USA 108, 5831–5836 (2011).

    CAS  PubMed  Google Scholar 

  81. 81

    Weaver, I.C. et al. Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J. Neurosci. 25, 11045–11054 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Meaney, M.J. & Szyf, M. Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues Clin. Neurosci. 7, 103–123 (2005).

    PubMed  PubMed Central  Google Scholar 

  83. 83

    Elliott, E., Ezra-Nevo, G., Regev, L., Neufeld-Cohen, A. & Chen, A. Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice. Nat. Neurosci. 13, 1351–1353 (2010).

    CAS  PubMed  Google Scholar 

  84. 84

    Moncek, F., Duncko, R., Johansson, B.B. & Jezova, D. Effect of environmental enrichment on stress related systems in rats. J. Neuroendocrinol. 16, 423–431 (2004).

    CAS  PubMed  Google Scholar 

  85. 85

    LaPlant, Q. et al. Role of nuclear factor κB in ovarian hormone-mediated stress hypersensitivity in female mice. Biol. Psychiatry 65, 874–880 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Conrad, C.D., Grote, K.A., Hobbs, R.J. & Ferayorni, A. Sex differences in spatial and non-spatial Y-maze performance after chronic stress. Neurobiol. Learn. Mem. 79, 32–40 (2003).

    PubMed  Google Scholar 

  87. 87

    Galea, L.A. et al. Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress. Neuroscience 81, 689–697 (1997).

    CAS  PubMed  Google Scholar 

  88. 88

    Bowman, R.E., Beck, K.D. & Luine, V.N. Chronic stress effects on memory: sex differences in performance and monoaminergic activity. Horm. Behav. 43, 48–59 (2003).

    CAS  PubMed  Google Scholar 

  89. 89

    Wood, G.E. & Shors, T.J. Stress facilitates classical conditioning in males, but impairs classical conditioning in females through activational effects of ovarian hormones. Proc. Natl. Acad. Sci. USA 95, 4066–4071 (1998).

    CAS  PubMed  Google Scholar 

  90. 90

    Wood, G.E., Beylin, A.V. & Shors, T.J. The contribution of adrenal and reproductive hormones to the opposing effects of stress on trace conditioning in males versus females. Behav. Neurosci. 115, 175–187 (2001).

    CAS  PubMed  Google Scholar 

  91. 91

    Autry, A.E., Adachi, M., Cheng, P. & Monteggia, L.M. Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior. Biol. Psychiatry 66, 84–90 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92

    Bowman, R.E., Ferguson, D. & Luine, V.N. Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats. Neuroscience 113, 401–410 (2002).

    CAS  PubMed  Google Scholar 

  93. 93

    Douglas, A.J., Brunton, P.J., Bosch, O.J., Russell, J.A. & Neumann, I.D. Neuroendocrine responses to stress in mice: hyporesponsiveness in pregnancy and parturition. Endocrinology 144, 5268–5276 (2003).

    CAS  PubMed  Google Scholar 

  94. 94

    Wilkinson, M.B. et al. A novel role of the WNT-dishevelled-GSK3β signaling cascade in the mouse nucleus accumbens in a social defeat model of depression. J. Neurosci. 31, 9084–9092 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Binder, E.B. et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. J. Am. Med. Assoc. 299, 1291–1305 (2008).

    CAS  Google Scholar 

  96. 96

    Ressler, K.J. et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 470, 492–497 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97

    Polanczyk, G. et al. Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension. Arch. Gen. Psychiatry 66, 978–985 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98

    Stein, M.B., Campbell-Sills, L. & Gelernter, J. Genetic variation in 5HTTLPR is associated with emotional resilience. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 150B, 900–906 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99

    Murrough, J.W. & Charney, D.S. The serotonin transporter and emotionality: risk, resilience, and new therapeutic opportunities. Biol. Psychiatry 69, 510–512 (2011).

    PubMed  Google Scholar 

  100. 100

    Domschke, K. et al. Neuropeptide Y (NPY) gene: impact on emotional processing and treatment response in anxious depression. Eur. Neuropsychopharmacol. 20, 301–309 (2010).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Preparation of this review was supported by grants from the US National Institute of Mental Health: R01 MH090264 (S.J.R.); K23 MH094707 (J.W.M.); R01 MH092306 (M.-H.H.); and R01 MH51399, P50 MH66172 and P50 MH96890 (E.J.N.).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Scott J Russo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Russo, S., Murrough, J., Han, MH. et al. Neurobiology of resilience. Nat Neurosci 15, 1475–1484 (2012). https://doi.org/10.1038/nn.3234

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing