HPA axis dysregulation and suicidal behavior in depression – Differentiation of a genetically distinct subgroup?

One of the most demanding tasks in psychiatry is to protect patients from suicidal behavior. More than 90% of the suicide victims have a diagnosis of some type of mood disorder. Postmortem and functional data in indicate a possible dysregulation of the hypothalamic-pituitary adrenal (HPA) axis activity. We applied the combined dexamethasone-suppression/CRH stimulation (Dex/CRH) test to 310 patients admitted with a depressive syndrome. Psychopathology was assessed using syndrome- and symptom-oriented scales, a thorough disease and family history for affective disorders and suicidal behavior was acquired. Whereas there was no difference in baseline and post-dexamethasone-suppression hormone levels regarding suicidal behavior we observed that depressed patients with suicidal ideation or attempt prior to admission showed a significantly lower cortisol and ACTH response to CRH stimulation compared to non-suicidal depressed patients. In general, depressed patients that attempted suicide in their disease history up to admission presented with a significantly lower cortisol response than those that never attempted suicide regardless of current suicidality. These findings suggest that depressed patients with suicidal behavior may represent a biological subgroup of depressed patients. To address the question whether this difference could be reflected on the genetic level we genotyped 56 SNPs in 8 candidate genes related to HPA axis activity.