Gene × Environment Determinants of Stress- and Anxiety-Related Disorders

Sharma, Sumeet K.; Powers, Abigail; Bradley, Bekh; Ressler, Kerry J.

doi:10.1146/annurev-psych-122414-033408

Cited by 115 publications

(80 citation statements)

References 80 publications

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“…Given the prominent role of stress in the development and exacerbation of affective disorders including major depression and PTSD1247, understanding the biological mechanisms contributing to inter-individual differences in stress-susceptibility could lead to the development of susceptibility biomarkers, novel treatments, and preventative approaches89. Here we provide converging pharmacological, physiological, and genetic evidence supporting increased 2-AG-CB1R signalling as an endogenous stress-resilience factor that buffers against adverse consequences of stress.…”

Section: Discussionmentioning

confidence: 75%

“…Stress is a major risk factor for neuropsychiatric disease, particularly major depression and anxiety disorders, and is etiologically causal in posttraumatic stress disorder (PTSD)1234567. Stress-resilience is associated with reduced risk of psychopathology and is an active process of adaptation, not merely the absence of maladaptive changes induced by stress exposure8910111213.…”

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confidence: 99%

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Endocannabinoid signalling modulates susceptibility to traumatic stress exposure

et al. 2017

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Stress is a ubiquitous risk factor for the exacerbation and development of affective disorders including major depression and posttraumatic stress disorder. Understanding the neurobiological mechanisms conferring resilience to the adverse consequences of stress could have broad implications for the treatment and prevention of mood and anxiety disorders. We utilize laboratory mice and their innate inter-individual differences in stress-susceptibility to demonstrate a critical role for the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) in stress-resilience. Specifically, systemic 2-AG augmentation is associated with a stress-resilient phenotype and enhances resilience in previously susceptible mice, while systemic 2-AG depletion or CB1 receptor blockade increases susceptibility in previously resilient mice. Moreover, stress-resilience is associated with increased phasic 2-AG-mediated synaptic suppression at ventral hippocampal-amygdala glutamatergic synapses and amygdala-specific 2-AG depletion impairs successful adaptation to repeated stress. These data indicate amygdala 2-AG signalling mechanisms promote resilience to adverse effects of acute traumatic stress and facilitate adaptation to repeated stress exposure.

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Section: Discussionmentioning

confidence: 75%

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confidence: 99%

Endocannabinoid signalling modulates susceptibility to traumatic stress exposure

et al. 2017

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“…Lastly, as there was a very small amount of the variance explained by the G × E interactions, the results may still be subject to the risk of reproducibility and insufficient sample size, which are considered problems related to candidate G × E interaction studies (Sharma, Powers, Bradley, & Ressler, ). Nonetheless, we obtained convergent results from using two relatively large samples after exposure to different types of stress.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y Gene × Environment Interaction Predicts Resilience and Positive Future Focus

Gan

Chen

Xiao

et al. 2019

Applied Psych Health & Well

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Background: The objective of this study was to investigate whether the NPY rs16147 polymorphism interacts with the environment to have an impact on resilience and positive future focus. Methods: In Study 1, 1,140 earthquake survivors were evaluated; self-reported trauma exposure level and resilience were reported. Study 2 included 2,370 company employees and university students; information regarding self-reported early stressful life events and positive future focus were obtained. Results: In both studies, the results showed a significant effect of interaction between the NPY rs16147 polymorphism and the level of stress on resilience. In Study 1, the T allele carriers reported consistent levels of resilience in low, moderate, and high levels of trauma exposure. In Study 2, the T genotype was associated with higher levels of positive future focus following early adversity. Conclusions: Our findings are discussed in light of the differential post-stress growth hypothesis.

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“…In human populations, stress and other anxiety related disorders, are caused by both genetic and environmental factors (Dick, 2011;Sharma et al, 2016). Several genome wide association studies (GWAS) have been conducted in search of genetic variants that predispose patients to anxiety and stress related disorders, and the heritability of these disorders has been calculated to be between 30-50% (True et al, 1993;Stein et al, 2002;Sartor et al, 2012).…”

Section: Genetic Contributions As Demonstrated By F1 and F2 Data Andmentioning

confidence: 99%

Analysis of stress responses inAstyanaxlarvae reveals heterogeneity among different populations

Chin

Loomis

Albert

et al. 2020

Preprint

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Research Highlight:• Cavefish populations of A. mexicanus have reduced stress relative to surface conspecific at larval stages • We show that a glucocorticoid receptor, a negative regulator of the neuroendocrine stress axis, is upregulated in stress-resistant cavefish • There exists much ontological heterogeneity between different cavefish populations. AbstractStress responses are conserved physiological and behavioral outcomes as a result of facing potentially harmful stimuli, yet in pathological states, stress becomes debilitating. Stress responses vary considerably throughout the animal kingdom, but how these responses are shaped evolutionarily is unknown. The Mexican cavefish has emerged as a powerful system for examining genetic principles underlying behavioral evolution. Here, we demonstrate that cave Astyanax have reduced behavioral and physiological measures of stress when examined at larval stages. We also find increased expression of the glucocorticoid receptor, a repressible element of the neuroendocrine stress pathway. Additionally, we examine stress in three different cave populations, and find that some, but not all, show reduced stress measures. Together, these results reveal a mechanistic system by which cave-dwelling fish reduced stress, presumably to compensate for a predator poor environment.

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Gene × Environment Determinants of Stress- and Anxiety-Related Disorders

Cited by 115 publications

References 80 publications

Endocannabinoid signalling modulates susceptibility to traumatic stress exposure

Endocannabinoid signalling modulates susceptibility to traumatic stress exposure

Neuropeptide Y Gene × Environment Interaction Predicts Resilience and Positive Future Focus

Analysis of stress responses inAstyanaxlarvae reveals heterogeneity among different populations

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