Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression.
The discovery that stress and depression, as well as other psychiatric illnesses, are characterized by structural alterations, and that these changes result from atrophy and loss of neurons and glia in specific limbic regions and circuits, has contributed to a fundamental change in our understanding of these illnesses. These structural changes are accompanied by dysregulation of neuroprotective and neurotrophic signaling mechanisms that are required for the maturation, growth, and survival of neurons and glia. Conversely, behavioral and therapeutic interventions can reverse these structural alterations by stimulating neuroprotective and neurotrophic pathways and by blocking the damaging, excitotoxic, and inflammatory effects of stress. Lifetime exposure to cellular and environmental stressors and interactions with genetic factors contribute to individual susceptibility or resilience. This exciting area of research holds promise and potential for further elucidating the pathophysiology of psychiatric illness and for development of novel therapeutic interventions.
Duman
Ronald S
RS
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA. ronald.duman@yale.edu
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology / Q000628:therapy
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents