Relationship of object loss during development to hypothalamic-pituitary-adrenal axis function during major affective illness later in life.

Although many studies have attempted to determine whether early object loss influences the risk of developing major affective illness in adulthood, there are few empirical data relating early loss to subsequent hypothalamic-pituitary-adrenal (HPA) axis dysfunction in adulthood. Forty-five psychiatric inpatients admitted for an active major affective illness, all of whom had a previous history of a significant permanent object loss (by death only), were studied retrospectively in this preliminary investigation to examine whether the type and timing of object loss experienced earlier in life would discriminate affectively ill patients who exhibit HPA dysfunction. Several loss variables were found to be statistically significant predictors of cortisol responses following glucocorticoid challenge. A median split of the distribution was used to classify patients into early loss (< or = 19 years) and late loss (> or = 20 years) groups. Analyses for all subjects, early and late loss combined, showed that late loss was associated with higher 11 p.m. cortisol levels. Within the early loss group, however, age of first loss was the most significant predictor of 4 p.m. cortisol levels after dexamethasone challenge. Consistent with the hypothesis that childhood object loss may be associated with long-term alterations in HPA axis function, younger age of loss correlated significantly with higher 4 p.m. cortisol responses. These preliminary data suggest that future prospective investigation of the neurobiological as well as psychosocial consequences of various types of early loss warrant further study.