Cortisol and depression in pre-diagnosed and early stage Huntington's disease

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction and depression have both been shown to occur in Huntington's disease (HD) gene carriers prior to diagnosis (pre-HD) and in diagnosed HD patients. However, the relationship between HPA axis dysfunction and the severity of depressive symptomatology in pre-HD and early-HD has not been systematically examined, despite morning hypercortisolism being a characteristic feature of some subtypes of idiopathic depression. The aim of this study was to investigate whether HPA axis function is related to levels of depression in pre-HD and early-HD. To assess HPA axis function we obtained salivary cortisol concentrations from 20 controls, 20 pre-HD, and 17 early-HD participants at four time points over a 24h period. Depression symptoms were assessed using the Inventory of Depressive Symptomatology - Self-Report. Of the participants who were found not to be depressed, the early-HD group had significantly lower morning cortisol levels relative to pre-HD and controls. In contrast, the early-HD group with at least mild or greater levels of depression symptoms had a comparable cortisol concentration to pre-HD and controls. The results suggest that early-HD may be associated with hypocortisolism. However when depressed, a hyperactive HPA axis response may still be induced in early-HD and lead to cortisol levels that are similar to pre-HD and controls. Our study reveals that cortisol levels in HD may be modified by the presence or absence of depressive symptomatology. Depression may be an important factor for understanding how the HPA axis is affected in HD, particularly in the morning.