CLINICAL AND MAGNETIC-RESONANCE-IMAGING CORRELATES OF HYPOTHALAMIC-PITUITARY-ADRENAL AXIS FUNCTION IN DEPRESSION AND ALZHEIMERS-DISEASE

Background. An age-related dysregulation of the hypothalamic-pituitary -adrenal (HPA) axis is well recognised in animals, but still remains c ontroversial in humans. There is increasing interest that raised corti costeroid levels, due to activation of the HPA axis, may cause both de pressive symptoms and cognitive impairments. Steroid effects on cognit ion may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory. Method. To investigate this further, we examined the relationship between the de xamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 norm al controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM-III-R Major Depression. Results. Controlling for dif ferences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subject s. However, among subjects with Alzheimer's disease, post-dexamethason e cortisol levels were independently associated with both minor depres sive symptoms and hippocampal atrophy on MRI. Conclusion. An associati on between advancing age and increased HPA axis dysregulation is suppo rted for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal d irection of these associations.