The Interface of Stress and the HPA Axis in Behavioural Phenotypes of Mental Illness

Abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function are one of the most consistent biological findings across several mental disorders, but many of the mechanisms underlying this abnormality as well as the potential contribution to behavioural phenotypes remain only partially understood. Interestingly, evidence suggests a U-curve, with dysregulation of the HPA axis towards both hyper- or hypoactivity manifesting as a risk to mental wellbeing. This review will elaborate on both the clinical and molecular role of the neuroendocrine stress system in depressive, psychotic and post-traumatic stress disorders and present some of the most recent findings that have shed light on the complex interface between environmental stressors, molecular mechanisms and clinical presentation. Crucially, plasticity of the HPA axis confers both vulnerability to adverse events, particularly so in early developmental stages, as well as hope for the treatment of mental disorder, as evidenced by changes in HPA functioning associated with remission of symptoms.