HORMONAL RESPONSE PATTERN IN THE COMBINED DEX-CRH TEST IS STABLE OVERTIME IN SUBJECTS AT HIGH FAMILIAL RISK FOR AFFECTIVE-DISORDERS

One of the major neurobiological alterations in depressive disorders c onsists in a disturbed regulation of the hypothalamic-pituitary-adreno cortical (HPA) system. This is reflected by a pathological increase in the adrenocorticotropin (ACTH) and cortisol release after pretreatmen t with 1.5 mg dexamethansone (DEX) the previous night and a challenge with 100 mu g corticotropin-releasing hormone (CRH) the next day. The changes evoked by this combined DEX-CRH test recede partially with an improvement of the psychopathological symptoms of depressed patients. It is still unclear, however, whether this long-lasting disturbance of the HPA system is due to acquired changes in the acute illness or whe ther it plays a causal role and could be considered as a trait or vuln erability marker for depression. In a previous study we have examined the HPA function of healthy probands with a high genetic load for affe ctive disorders. We found that this group of high-risk probands (HRPs) showed abnormal DEX-CRH test results with a cortisol release that was between that of a control group and a group of patients with depressi on. In a follow-up study we now reexamined 14 of the 47 HRPs about 4 y ears after the index investigation and found surprisingly constant DEX -CRH test results, so that one of the requirements for a vulnerability marker is fulfilled. (C) 1998 American College of Neuropsychopharmaco logy. Published by Elsevier Science Inc.