Childhood adversity and the cortisol awakening response in depression: A meta-analysis

Although cortisol awakening response (CAR) dysregulation is frequently documented among individuals with depression, there is conflicting evidence regarding the direction and degree of dysregulation, which impedes our ability to provide personalized and efficacious treatment. Childhood adversity is posited to explain variability within the CAR-depression literature, but the effect of childhood adversity on the CAR in depression has not yet been quantified. We meta-analyzed 19 studies (n = 2053) examining the association between childhood adversity and the CAR among individuals with depression. Data were pooled using random-effects models for childhood adversity overall, childhood adversity characterized by threat, and childhood adversity characterized by deprivation. Among individuals with depression, greater exposure to childhood adversity was associated with a steeper CAR. Further, in line with hypotheses, among individuals with depression, greater exposure to childhood adversity characterized by threat was associated with a steeper CAR, whereas greater exposure to adversity characterized by deprivation was not. These results support the proposition that greater childhood adversity, and in particular adversity characterized by threat, could lead to a distinct presentation of depression characterized by dysregulated diurnal HPA axis activity, as evidenced by a steeper CAR. These findings suggest specificity in the associations between types of childhood adversity and the CAR and could inform growing efforts towards personalized medicine in the treatment of depression.