Neurobiological Pathways between Chronic Stress and Depression: Dysregulated Adaptive Mechanisms?

Stress-related diseases have been predicted to become major contributors to the Global Disease Burden within the next 20 years. Of these, depression is one of the principal identifiable sources of concern for public mental health, and has been hypothesized to be an outcome of prolonged stress. Examination of the hyper-responsiveness of the Hypothalamic-Pituitary-Adrenal axis, consequent elevated serum cortisol, plus the effects of this upon brain structure and function, provides a model for understanding how chronic stress may be a causal vector in the development of depression. Evidence from studies of the effectiveness of antidepressants aimed at reducing cortisol within depressed patients supports this model and suggests avenues for future research and treatment of stress-induced depression.