Neurobiology of resilience

In the paper

“Our initial analysis showed that the firing rate of VTA dopamine neurons was normal in resilient animals and increased in susceptible animals”

What the sources say

• Not checked yetcites [24] Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007). source

In the paper

“sub–chronic unpredictable stress induces anhedonia (decreased sucrose preference), increased immobility on the forced swim test, and increased anxiety (greater latency to feed in a novel environment and decreased time grooming in the splash test).”

What the sources say

• Not checked yetcites [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). source

In the paper

“a contrary report linked elevated DHEA to increased suicidality in male veterans with PTSD11”

What the sources say

• Not checked yetcites [11] Butterfield, M.I. et al. Neuroactive steroids and suicidality in posttraumatic stress disorder. Am. J. Psychiatry 162, 380–382 (2005). source

In the paper

“stress exposure and adverse life events are important risk factors for both disorders.”

In the paper

“such resilience—the ability to avoid deleterious behavioral changes in response to chronic stress—is mediated not only by the absence of key molecular abnormalities which occur in susceptible animals to impair their coping ability, but also by the presence of novel molecular adaptations which occur uniquely in resilient individuals to help promote normal behavioral function.”

In the paper

“Numerous studies have reported elevated blood glucocorticoid levels in roughly two–thirds of individuals with MDD, although a smaller subset of depressed individuals show reduced glucocorticoid levels and typically display less severe symptoms4.”

What the sources say

• Not checked yetcites [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). source

In the paper

“In both men and woman, testosterone increases in “winners” following an athletic competition and, on average, athletes with the highest saliva testosterone levels have higher rankings within the team13.”

What the sources say

• Not checked yetcites [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). source

In the paper

“Testosterone levels are also positively correlated with the degree of social connectedness with teammates, greater feelings of personal success and dominance14.”

What the sources say

• Not checked yetcites [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). source

In the paper

“Reports have shown that blood DHEA levels increase under acute stress and that a higher level of DHEA, or a higher DHEA to cortisol ratio, is associated with less dissociative symptoms and superior performance in healthy subjects undergoing military survival training9.”

What the sources say

• Not checked yetcites [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). source

In the paper

“a separate study found that DHEA levels were elevated in PTSD but that higher levels were correlated with symptom improvement and better coping while a lower DHEA to cortisol ratio was positively correlated with the severity of PTSD symptoms10.”

What the sources say

• Not checked yetcites [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). source

In the paper

“It has been reported that DHEA responses to adrenocorticotropic hormone (ACTH) were elevated in PTSD and negatively correlated with the severity of symptoms, suggesting that DHEA release during stress may buffer the severity of PTSD 9.”

What the sources say

• Not checked yetcites [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). source

In the paper

“Hypocortisolemia has also been reported widely in PTSD; however, here too the findings have been mixed5.”

What the sources say

• Not checked yetcites [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). source

In the paper

“Increased cerebrospinal fluid levels of corticotropin releasing hormone (CRH) have been documented more generally in adults who report a history of childhood abuse6, and thus does not always correlate with the development of MDD or PTSD7, 8.”

What the sources say

• Not checked yetcites [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). source
• Not checked yetcites [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). source
• Not checked yetcites [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). source

In the paper

“The ability to avoid such deleterious consequences of stress in turn depends on both passive and active resilience mechanisms.”

In the paper

“Cohen et al.23 recently utilized a predator odor to induce a stress response and then classified rats into 3 groups; one-third each that was extremely disrupted, partially disrupted, or minimally disrupted. The classifications were based largely on the number and type of behavioral deficits and the degree of change in brain NPY levels.”

What the sources say

• Not checked yetcites [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). source

In the paper

“Depending on the severity and duration of exposure to inescapable foot shock, a subset of animals, ~30% in some studies, develop learned helplessness—they fail to escape when escape becomes possible, while another subset (termed resilient) escapes with latencies seen in unstressed animals29.”

What the sources say

• Not checked yetcites [29] Berton, O. et al. Induction of deltaFosB in the periaqueductal gray by stress promotes active coping responses. Neuron 55, 289–300 (2007). source

In the paper

“resilient animals are not devoid of symptoms and, in fact, exhibit some behavioral adaptations that appear maladaptive, but they exhibit clear resistance to many other maladaptive sequelae of the chronic social stress.”

In the paper

“Early studies in men suggest that testosterone may be effective in treatment–resistant depression and as an adjunct to SSRI treatment17.”

What the sources say

• Not checked yetcites [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). source

In the paper

“the definition of resilience, and the percent of animals exhibiting resilience, varies across several stress paradigms.”

In the paper

“higher blood NPY levels were shown to predict better performance under stress during military survival training and were found in Special Forces soldiers, compared to their non–Special Forces military counterparts18.”

What the sources say

• Not checked yetcites [18] Morgan, C.A. III et al. Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biol. Psychiatry 47, 902–909 (2000). source

In the paper

“Neuropeptide Y (NPY), a peptide neurotransmitter, modulates stress responses in animals, and studies in humans support the possibility that NPY may represent a protective factor in the face of stress18, 19.”

What the sources say

• Not checked yetcites [18] Morgan, C.A. III et al. Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biol. Psychiatry 47, 902–909 (2000). source
• Not checked yetcites [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). source

In the paper

“Maier and colleagues view the risk of learned helplessness to be highly dependent upon the animal’s own control over the stress, with resilience promoted by control over cessation of the stress (For review see 30).”

What the sources say

• Not checked yetcites [30] Fleshner, M., Maier, S.F., Lyons, D.M. & Raskind, M.A. The neurobiology of the stress-resistant brain. Stress 14, 498–502 (2011). source

In the paper

“10 days of social defeat in C57BL6/J mice results in ~35% resilient mice, while other strains such as CD1 or FVB are closer to 100% resilient 27.”

What the sources say

• Not checked yetcites [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). source

In the paper

“Genetic factors are important determinants for the risk or resilience to psychiatric disorders.”

In the paper

“following chronic social defeat stress, all genetically inbred C57BL6/J male mice exhibit a constellation of symptoms including heightened reactivity of the HPA axis, deficits in exploratory–based behavior that are interpreted as increased anxiety, and stress–induced polydipsia24.”

What the sources say

• Not checked yetcites [24] Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007). source

In the paper

“Strain–dependent responses to other physical stressors such as restraint or CMS have been shown, underscoring the role of complex genetics in regulating risk and resilience to chronic stress32–34.”

What the sources say

• Not checked yetcites [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). source
• Not checked yetcites [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). source
• Not checked yetcites [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). source

In the paper

“higher levels of NPY in response to acute stress predicted less psychological distress and fewer symptoms of dissociation19.”

What the sources say

• Not checked yetcites [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). source

In the paper

“The remaining animals, which have been termed resilient in some studies, usually exhibit some deleterious symptoms in response to the stress, but do not exhibit deficits in key behavioral domains.”

In the paper

“The animals classified as extremely disrupted exhibited anxiety–like behaviors and increased acoustic startle responses, as well as large reductions in NPY across multiple brain regions.”

What the sources say

• Not checked yetcites [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). source

In the paper

“CMS did not reduce hippocampal volume or alter glutamate metabolism in resilient mice as seen in susceptible mice.”

What the sources say

• Not checked yetcites [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). source

In the paper

“The shape of the inverted U differs by many factors including sex, strain, and behavioral domain in question (Fig. 2).”

What the sources say

• Not checked yetcites [50] McEwen, B.S. & Gianaros, P.J. Stress- and allostasis-induced brain plasticity. Annu. Rev. Med. 62, 431–445 (2011). source

In the paper

“we have shown that susceptible mice also avoid non–aggressive C57BL6/J littermates, and that such social avoidance is essentially permanent—it persists for >6 months—despite housing with non–aggressive littermates, suggesting that it does reflect a maladaptive response36, 38.”

What the sources say

• Not checked yetcites [36] Berton, O. et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311, 864–868 (2006). source
• Not checked yetcites [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). source

In the paper

“Compared to non–separated monkeys, previously separated monkeys showed fewer signs of anxiety and increased exploration of the environment coupled with diminished plasma levels of cortisol and ACTH44.”

What the sources say

• Not checked yetcites [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). source

In the paper

“Our group has defined resilience to chronic social defeat stress as the absence of social avoidance, anhedonia, and metabolic syndrome, which are highly correlated with one another24, 27, 28, 36.”

What the sources say

• Not checked yetcites [24] Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007). source
• Not checked yetcites [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). source
• Not checked yetcites [28] Lutter, M. et al. The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat. Neurosci. 11, 752–753 (2008). source

In the paper

“while female rodents tend to be more susceptible to stress–induced dysfunction in emotional domains (i.e., sucrose preference and forced swim test), they tend to show a greater degree of stress resilience in cognitive domains (i.e., object placement and recognition) (for review see51).”

What the sources say

• Not checked yetcites [51] Luine, V. Sex differences in chronic stress effects on memory in rats. Stress 5, 205–216 (2002). source

In the paper

“Separated monkeys also demonstrated enhanced response inhibition to previously rewarding stimuli, suggesting improved cognitive control of behavior45.”

What the sources say

• Not checked yetcites [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). source

In the paper

“During social defeat stress, animals that engage in less submissive posturing during the attack show less social avoidance, suggesting that this behavioral coping strategy may affect the aggressive interaction and thereby lessen the effects of the stress55.”

What the sources say

• Not checked yetcites [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). source

In the paper

“McEwen and colleagues systematically measured the type, length, and quality of stress experience on multiple rat behaviors and found that stress affects most behavioral domains with an inverted U–shape curve, where low and high levels of stress both impair behavior, while intermediate levels actually promote positive coping responses (for review see50).”

What the sources say

• Not checked yetcites [50] McEwen, B.S. & Gianaros, P.J. Stress- and allostasis-induced brain plasticity. Annu. Rev. Med. 62, 431–445 (2011). source

In the paper

“These and related findings highlight the critical window of stress exposure and suggest that early intermittent separations enhance stress tolerance, i.e., promotes resilience.”

In the paper

“coping with moderate amounts of stress leads to an individual sense of mastery and promotes resilience in the future.”

In the paper

“The anhedonic and metabolic symptoms are clearly maladaptive and indeed are reversed by chronic administration of antidepressants to susceptible mice36, 37.”

What the sources say

• Not checked yetcites [36] Berton, O. et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311, 864–868 (2006). source
• Not checked yetcites [37] Covington, H.E. III et al. Antidepressant actions of histone deacetylase inhibitors. J. Neurosci. 29, 11451–11460 (2009). source

In the paper

“This inverted U shape relationship between stress and coping can be observed in all organisms throughout their lifetime and suggests that maintaining optimal stress exposure might prevent the development of major psychiatric dysfunction.”

In the paper

“resilience in both children and adults is a common outcome following adversity – representing successful, adaptive coping in the face of stress39, 40.”

What the sources say

• Not checked yetcites [39] Masten, A.S. Ordinary magic. Resilience processes in development. Am. Psychol. 56, 227–238 (2001). source
• Not checked yetcites [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). source

In the paper

“there is some evidence that more graded exposure of adults to stress might reduce such vulnerabilities, that is, promote resilience.”

In the paper

“Within the general population, between 50–60% experience a severe trauma, yet the prevalence of illness is estimated to be only 7.8%41.”

What the sources say

• Not checked yetcites [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). source

In the paper

“an AMPA glutamate receptor subunit that reduces the Ca2+ permeability and overall conductance of AMPA channels71”

What the sources say

• Not checked yetcites [71] Vialou, V. et al. DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nat. Neurosci. 13, 745–752 (2010). source

In the paper

“there is an independent, active process occurring in resilient mice that normalizes VTA firing to control levels and thus prevents social avoidance and sucrose preference deficits”

What the sources say

• Not checked yetcites [24] Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007). source

In the paper

“such induction of K+ channels functionally occludes the increased Ih current and thereby actively promotes behavioral resilience24, 73”

What the sources say

• Not checked yetcites [24] Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007). source
• Not checked yetcites [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). source

In the paper

“Early intermittent maternal separations that promote resilience increase cortical volume within ventromedial PFC (VMPFC)66, changes opposite in direction to those seen in depressed humans and stressed rodents.”

What the sources say

• Not checked yetcites [66] Katz, M. et al. Prefrontal plasticity and stress inoculation-induced resilience. Dev. Neurosci. 31, 293–299 (2009). source

In the paper

“environmental enrichment similarly increases the complexity of the dendritic tree, dendritic spine density, and synaptic protein levels of pyramidal neurons in hippocampus and PFC”

What the sources say

• Not checked yetcites [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). source

In the paper

“most would argue for hypoactivity of NAc in depression, which is supported by deep brain stimulation studies that show electrical stimulation of the anterior limb of the internal capsule (which includes NAc) alleviates symptoms of depression and anxiety.”

In the paper

“chronic stress reduces dendritic arborization and glutamatergic dendritic spine density of pyramidal neurons in PFC and hippocampus, and reduces hippocampus neurogenesis, while increasing dendritic spine number or branching in amygdala and NAc (for review see63).”

What the sources say

• Not checked yetcites [63] Christoffel, D.J., Golden, S.A. & Russo, S.J. Structural and synaptic plasticity in stress-related disorders. Rev. Neurosci. 22, 535–549 (2011). source

In the paper

“The therapeutic implications of these findings are important and can pave the way for an innovative new approach to drug development for a range of stress–related syndromes.”

• Also stated in: § Introduction · plain

  “we conclude with a discussion of how this growing body of knowledge can guide the development of novel treatments for a range of stress–related disorders by enhancing such natural mechanisms of resilience.”

In the paper

“Numerous studies suggest that depression and anxiety in humans result in part from hypo–activation and reduced volume of frontal cortical and hipppocampal regions that control subcortical structures such as nucleus accumbens (NAc) and amygdala, although hyper–activation of certain PFC regions (e.g., subgenual area of anterior cingulate cortex) is also involved58–61.”

What the sources say

• Not checked yetcites [58] Price, J.L. & Drevets, W.C. Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192–216 (2010). source
• Not checked yetcites [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). source
• Not checked yetcites [60] Mayberg, H.S. Targeted electrode-based modulation of neural circuits for depression. J. Clin. Invest. 119, 717–725 (2009). source
• Not checked yetcites [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). source

In the paper

“Hypoactive PFC and hippocampal inputs to neurons in these subcortical structures may mediate their activation and the subsequent activity–dependent structural plasticity of their dendrites, although further research is needed in this area.”

In the paper

“Increased expression of these immediate early genes would suggest increased neuronal activation within this brain region, which might represent a pro–resilience adaptation.”

In the paper

“One recent paper found an epigenetic mechanism, induced by chronic stress in resilient mice only, that controls HPA axis hyperactivity83”

What the sources say

• Not checked yetcites [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). source

In the paper

“removal of ovarian hormones decreases the pro–depressant or anxiogenic effects of stress, while simultaneously increasing the negative effects of stress on spatial and non–spatial memory85, 91, 92”

What the sources say

• Not checked yetcites [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). source
• Not checked yetcites [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). source
• Not checked yetcites [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). source

In the paper

“the literature suggests that on cognitive domains females cope better with chronic forms of stress, whereas males tend to cope better with acute stress.”

In the paper

“increased excitability of VTA dopamine neurons mediates susceptibility, with normalization mediating resilience”

In the paper

“high levels of maternal care are associated with decreased DNA methylation of the GR gene, higher levels of GR expression, greater feedback inhibition of the HPA axis, and resilient stress responses in adulthood (for review see 81)”

What the sources say

• Not checked yetcites [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). source

In the paper

“Stress enhances the performance of female rodents on the radial arm maze, Morris water maze, Y–maze, non–associative learning, and object placement tasks, whereas stress impairs male performance in these assays86–88.”

What the sources say

• Not checked yetcites [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). source
• Not checked yetcites [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). source
• Not checked yetcites [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). source

In the paper

“there is not a one–to–one correspondence between reward and resilience. Not all molecular changes in the VTA or NAc that increase drug or natural reward promote resilience, and vice versa.”

In the paper

“prenatal exposure to glucocorticoids increases CRH levels in the central nucleus of amygdala and reduces volume of PFC structures in adulthood70”

What the sources say

• Not checked yetcites [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). source

In the paper

“increased firing of VTA dopamine neurons has long been documented in response to rewards as well as to aversive stimuli, and it has been suggested that they increase salience for both types of stimuli24, 73–76”

What the sources say

• Not checked yetcites [24] Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007). source
• Not checked yetcites [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). source
• Not checked yetcites [74] Goto, Y., Otani, S. & Grace, A.A. The Yin and Yang of dopamine release: a new perspective. Neuropharmacology 53, 583–587 (2007). source
• Not checked yetcites [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). source
• Not checked yetcites [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). source

In the paper

“which induces depression– and anxiety–like behavioral abnormalities49 and promotes susceptibility to chronic social defeat stress71”

What the sources say

• Not checked yetcites [49] Wallace, D.L. et al. CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. Nat. Neurosci. 12, 200–209 (2009). source
• Not checked yetcites [71] Vialou, V. et al. DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nat. Neurosci. 13, 745–752 (2010). source

In the paper

“after chronic social defeat stress, Crh gene expression is increased in the paraventricular nucleus (PVN) of hypothalamus of susceptible animals and that this adaptation is necessary for the development of social avoidance83”

What the sources say

• Not checked yetcites [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). source

In the paper

“in tests of acute stress or aversive conditioning, stress enhances learning in males and impairs it in females89, 90”

What the sources say

• Not checked yetcites [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). source
• Not checked yetcites [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). source

In the paper

“The observation that such approaches significantly reduce PTSD severity supports the view that targeting underlying biological mechanisms of stress inoculation may provide us with novel protein targets for new medications that further promote resilience in at–risk populations.”

In the paper

“Such treatments might be understood as being analogous to stress inoculation in that experiencing more moderate levels of stress, combined with techniques that reduce physiological and psychological perception of the trauma, can promote positive coping responses.”