High neuroticism and depressive temperament are associated with dysfunctional regulation of the hypothalamic-pituitary-adrenocortical system in healthy volunteers

Objective: Elevated neuroticism, depressive temperament and dysfunctional regulation of the hypothalamic-pituitary-adrenocortical (HPA) system are considered as risk factors for unipolar depression. An interaction of these vulnerability factors was suggested, but controversially discussed. In absence of other informative studies we set out for a replication test and for elucidation of the underlying mechanism. Method: Ninety-two subjects recruited in the community-performed assessments of personality and temperament as well as measurement of HPA function with the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Results: Cortisol levels subsequent to Dex/CRH challenge were associated with neuroticism; high-neuroticism subjects revealed a higher HPA activation. This difference was mainly because of male subjects greater than or equal to25 years. A similar relationship was observed for depressive temperament. Conclusion: This constellation may propose that HPA dysregulation is the endocrinological basis for neuroticism and depressive temperament; this result supports the view that distinct personality factors and HPA vulnerability interact in mediating depression.