Neuroendocrine Probes as Biological Markers of Affective Disorders: New Directions*

Abstract

Numerous endocrine abnormalities are found in depressive illness and, among these, several have been proposed as useful markers in diagnosis, prediction of treatment response, monitoring treatment outcome or in understanding of etiology. This paper reviews five endocrine systems — the hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, growth hormone regulation, prolactin regulation and pineal function, in which such abnormalities have been reported. The dexamethasone suppression test (DST) results are affected by a variety of other diseases and confounding conditions. Furthermore, variability in dexamethasone availability has recently been shown to be an important factor, influencing post-DST cortisol levels. Refined tests, taking into account all these factors, or alternative tests of hypothalamic-pituitary-adrenal function may lead to improved clinical utility. Pineal function is now the focus of considerable investigation. Low nocturnal output of melatonin is found in unipolar and bipolar affective disorder and is normalized by treatment with antidepressant drugs which block re-uptake of noradrenaline. These findings support the hypothesis of noradrenergic abnormality in depression. In seasonal affective disorder there is evidence for a phase delay in the melatonin rhythm which may be a key factor in the seasonal disorder. Effective light therapy causes a phase advance in the abnormal melatonin rhythm. Whether the normalization of the melatonin rhythm is instrumental in producing the antidepressant effect is yet to be determined. There are wide spread neuroendocrine abnormalities in depressive illness. These abnormalities encompass many different pituitary hormones, as well as the pineal. Major theories of affective disorder attribute the mood and visceral changes to disruption in central neurotransmitter regulation or to altered central regulation of body rhythms, or to both. It is thought that disruption of these central systems give rise not only to the mood and visceral changes, but to the accompanying changes in endocrine regulation. Current diagnostic practice is to use clinical history and observation to identify typical forms of depression. Such an approach to diagnosis is less useful in delineating atypical, borderline or sub-clinical affective disorder. For these reasons, the endocrine changes have been proposed as biological markers to be used as clinical aids in diagnosis, prediction of treatment response, monitoring treatment outcome and in understanding etiology. This paper reviews and evaluates published data on five such endocrine measures.