Abnormal stress responsiveness and suicidal behavior: A risk phenotype

Suicidal behavior is a major cause of morbidity and mortality in psychiatric illness. However, only a subset of patients with psychiatric illnesses, such as major depressive disorder (MDD), commit suicide. This raises the question of how those who manifest suicidal behavior differ from those who do not. In the context of a stress-diathesis model of suicidal behavior, the reaction to stress has often been overlooked. The hypothalamic-pituitary-adrenal (HPA) axis dysfunction is proposed as an index of a disordered response to stress that thereby is part of the pathogenesis of risk for suicide in major depression. Suicide attempters are distinguished from non-attempters by a cluster of traits that include greater mood dysregulation and subjective distress, more pronounced reactive aggressive traits, impaired problem solving and learning, and distortion of perceived social cues. In this review, we show how these traits and risk for suicide are potentially linked to HPA axis dysfunction, which in turn can be traced back to genetic predisposition, and early life stress-related epigenetic mechanisms.