Individual differences in the neurobiology of social stress: implications for depression-cardiovascular disease comorbidity

Abstract

Stress initiates a cascade of complex neural and peripheral changes that promote healthy adaption to stress, but when unabated, leads to pathology. Fascinating individual differences arise in the ability to cope with a stressor, rendering an individual more or less likely to develop stress-induced pathologies such as depression, anxiety, and cardiovascular disease. In this review we evaluate recent findings that investigate the neural underpinnings of adopting a passive or active coping response during social defeat stress. Because passive coping is associated with vulnerability to stress-related pathologies and active coping confers resiliency, understanding neurobiological adaptations associated with these diverse coping strategies may reveal biomarkers or targets impacting stress susceptibility. The co-occurrence of stress-induced depression and cardiovascular disease is becoming increasingly clear. Therefore this review focuses on the central mechanisms capable of contributing to psychopathology and cardiovascular disease such as corticotropin releasing factor, neuropeptide Y, monoamines, cytokines and oxidative stress. The impetus for this review is to highlight neurobiological systems that warrant further evaluation for their contribution to the pathophysiology of depression-cardiovascular disease comorbidity.

Keywords: Resident-intruder paradigm; coping; corticotropin releasing factor; dorsal raphe.; locus coeruleus.

Fig. (1)

Distinct consequences of passive and active coping during social defeat stress. Based on studies from our lab and others we postulate that rats characterized by a passive coping strategy (A) exhibit neurobiological adaptations leading to stress vulnerability and include increases in the CRF, noradrenergic, proinflammatory cytokine and oxidative stress systems. These stress-induced changes within the brain lead to reductions in heart rate variability (HRV), increased cardiac hypertrophy, and translate to a depressive-like phenotype. Alternatively, actively coping during social stress (B) leads to a distinct sequence of adaptions; stress results in reductions in the CRF and NE systems within the brain. Additionally, neuroinflammation and oxidative stress (ROS) is reduced and NPY and serotonergic systems are enhanced. These central changes promote resilience in the face of adversity and may prevent decreases in HRV and the development of depressive-like behaviors.