PERSISTENT CHANGES IN CORTICOTROPIN-RELEASING FACTOR SYSTEMS DUE TO EARLY-LIFE STRESS - RELATIONSHIP TO THE PATHOPHYSIOLOGY OF MAJOR DEPRESSION AND POSTTRAUMATIC-STRESS-DISORDER

In addition to a genetic contribution to the vulnerability for mood an d anxiety disorders, such as major depressive disorder (MDD) and post- traumatic stress disorder (PTSD), a preeminent role of early adverse l ife events in the pathogenesis of these disorders has been postulated. Corticotropin releasing factor (CRF), which has been conclusively doc umented to be the major regulator of the mammalian stress response, ma y be the seminal neurobiological substrate mediating the effects of ea rly life stress on subsequent psychopathology. Central administration of CRF produces many of the physiological and behavioral effects of st ress and of anxiety and depression. Clinical studies have provided evi dence for increased activation of CRF neuronal systems in both MDD and PTSD. Similar hyperactivity of CRF neurons and sensitization of the p ituitary-adrenal stress response has been observed in adult animals ex posed to stress early in life. We propose that early adverse life even ts might render the human individual vulnerable to the effects of stre ss later in life, resulting in an increased risk for developing psycho pathology via long-lived alterations in CRF-containing neural circuits . Based on these findings, new therapies including early intervention can now be developed to treat individuals exposed to severe stress ear ly in life.