Persistent changes in corticotropin-releasing factor systems due to early life stress: relationship to the pathophysiology of major depression and post-traumatic stress disorder.
In addition to a genetic contribution to the vulnerability for mood and anxiety disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), a preeminent role of early adverse life events in the pathogenesis of these disorders has been postulated. Corticotropin releasing factor (CRF), which has been conclusively documented to be the major regulator of the mammalian stress response, may be the seminal neurobiological substrate mediating the effects of early life stress on subsequent psychopathology. Central administration of CRF produces many of the physiological and behavioral effects of stress and of anxiety and depression. Clinical studies have provided evidence for increased activation of CRF neuronal systems in both MDD and PTSD. Similar hyperactivity of CRF neurons and sensitization of the pituitary-adrenal stress response has been observed in adult animals exposed to stress early in life. We propose that early adverse life events might render the human individual vulnerable to the effects of stress later in life, resulting in an increased risk for developing psychopathology 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 early in life.
Heim
C
C
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Owens
M J
MJ
Plotsky
P M
PM
Nemeroff
C B
CB
D000328:Adult; D000818:Animals; D002648:Child; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000502:physiology*; D003866:Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008016:Life Change Events; D008255:Macaca radiata; D008297:Male; D051381:Rats; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology*
D003346:Corticotropin-Releasing Hormone