Influence of cocaine dependence and early life stress on pituitary–adrenal axis responses to CRH and the Trier social stressor

Summary Long-term changes in the hypothalamic–pituitary–adrenal (HPA) axis as a result of early life stress could be related to the development of substance use disorders during adulthood. In this study, the neuroendocrine, physiologic (HR), and subjective responses to corticotropin releasing hormone (CRH) and the Trier Social Stress Task (TSST) in individuals with cocaine dependence, with ( n = 21)/without early life stress ( n = 21), non-dependent individuals with early life stress ( n = 22), and a control group were examined ( n = 21). CRH increased cortisol and ACTH levels in all groups. However, a significant effect of early life stress on ACTH was observed indicating that the increase in ACTH was greatest in subjects with a history of childhood stress. Post hoc analysis indicated the early life stress/non-cocaine dependent individuals exhibited significantly higher levels of ACTH as compared to the early life stress/cocaine-dependent group. Despite the elevated ACTH response there was no difference between the groups in the cortisol response to CRH. The TSST produced a significant elevation in ACTH and cortisol all study groups. No significant group differences were observed. The subjective stress and peak heart rate responses to the TSST were greatest in cocaine-dependent subjects without early life stress. In response to CRH, subjective stress and craving were positively correlated in cocaine-dependent subjects regardless of early life stress history, while stress and craving following the TSST were correlated only in cocaine-dependent subjects without a history of early life stress. Findings support previous studies demonstrating that subjects with a history of childhood adversity exhibit elevated ACTH and blunted cortisol levels in response to stress. In contrast, HR and subjective stress in response to the TSST were greatest in cocaine-dependent subjects without a history of early life stress, suggesting that childhood adversity may desensitize autonomic and subjective responding to social stress in adults with cocaine dependence.