Post-dexamethasone arginine vasopressin levels in patients with severe mood disorders

There appears to be an allostatic shift in the hypothalamic-pituitary-adrenal (HPA) axis of animals exposed to chronic stress, such that vasopressinergic regulation of the HPA axis becomes critical for sustaining corticotroph responsiveness in the presence of high circulating glucocorticoid levels. It has been hypothesised that this is also a feature of patients with mood disorders and is mediated by a shift in hypothalamic drive in favour of arginine vasopressin (AVP) rather than corticotrophin releasing hormone (CRH), by up-regulation of AVP receptors in the pituitary and by a relatively reduced impact of glucocorticoid induced negative feedback on AVP release. We examined the latter, by comparing AVP levels after pretreatment with the glucocorticoid, dexamethasone in 41 bipolar patients (21 of whom were in full remission), 23 patients with chronic major depressive disorder and 21 healthy controls. We found that, as hypothesised, post-dexamethasone AVP levels were significantly elevated in patients with bipolar disorder and chronic depression compared with controls and also that there was no difference between symptomatic and remitted bipolar patients. The data shows that post-dexamethasone AVP levels are a sensitive measure of HPA axis function, that HPA axis dysfunction persists into euthymia in bipolar disorder and that, in contrast to previous reports, patients with chronic depression have a dysfunctional HPA axis.