Dexamethasone suppression tests in psychiatry: is there a place for an integrated hypothesis?

The abnormal performance of the DST in depressive illness has been shown to be one of the most reproducible findings in biological psychiatry. Initial claims of its very high diagnostic specificity for the diagnosis of endogenous depression have not been substantiated: an abnormal response appears to reflect a biological dysfunction that cuts across the clinically established boundaries of psychiatric nosology. This lack of diagnostic utility does not reduce its prognostic value and abnormal DST response may indicate or reflect a versatile component in psychiatric disturbance and could serve therefore to predict or monitor the effects of physical and psychological intervention. Contributory factors to abnormal DST response are explored: factors such as stress, nutrition and age are reviewed and discussed. Concepts of biogenetic (neurohumoral) and psychological (psychodynamic and psychosocial) vulnerability and initiation/promotion are invoked and an integrated hypothesis is suggested: emotional strain provokes neurohumoral and neuroendocrine changes; these changes lead to vegetative disturbances including loss of appetite and weight with subsequent nutritional deficiencies that promote/reverse their neurohumoral and neuroendocrine changes. The role of 5-hydroxytryptamine is emphasized. Supportive evidence for aspects of this hypothesis is provided including animal studies and studies of the clinical and biological correlates of abnormal DST response.