Vol 6 n° 2 - Neuroplasticity
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epression is a common, chronic, and often dis- abling psychiatric illness, which is estimated to affect 5% to 10% of the population. It frequently appears in early life, has a chronic course, and is considered a risk factor for other medical illnesses, such as coronary vascular dis- ease, diabetes, and osteoporosis.This is not altogether sur- prising given the extensive bidirectional “mind-body” interactions mediated via the autonomic nervous system, immune system, and a host of neuroendocrine factors. According to the World Health Organization (WHO), depression is the leading global cause of years of life lived with disability and the fourth leading cause of disability- adjusted   life-years.  Disability-adjusted   life-years   is defined as the reduction in an individual’s productive life, and takes into account premature mortality.1,2 Considering the high morbidity and mortality associated with depression, it is unfortunate that the psychological and neurobiological underpinnings of depression have not been specifically defined.Although major depression is currently diagnosed by means of a diagnostic system (Diagnostic  and  Statistical  Manual  of  Mental  Health Disorders, Fourth Edition [DSM-IV]) based upon phe- nomenology, this disorder most likely embodies a het- erogeneous   set   of   disorders   with   multiple   causes. Therefore, one of the major goals of current and future research on depression is the development of a diagnos- tic system based on etiology.3 This goal is becoming increasingly closer to reality due to recent progress in the identification of neural circuits, neurochemicals, and  signal  transduction  mechanisms 2 1 7 C l i n i c a l   r e s e a r c h D Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Cellular plasticity and resilience and the pathophysiology of severe mood disorders Dennis S. Charney, MD; Georgette DeJesus, MD; Husseini K. Manji, MD Keywords:  mood  disorder;  depression;  neuroplasticity;  stress;  resilience;  brain morphology Author affiliations: National Institute of Mental Health, Bethesda, Md, USA Address  for  correspondence:  Prof  Dennis  S.  Charney,  National  Institute  of Mental Health, 15K North Drive, Room 101, Bethesda, MD 20892-2670, USA (e-mail: charneyd@nih.gov) Recent advances in the identification of the neural cir- cuits, neurochemicals, and signal transduction mecha- nisms involved in the pathophysiology and treatment of mood  disorders  have  led  to  much  progress  toward understanding  the  roles  of  genetic  factors  and  psy- chosocial stressors. The monoaminergic neurotransmit- ter systems have received the most attention, partly because of the observation that effective antidepressant drugs exert their primary biochemical effects by regu- lating intrasynaptic concentrations of serotonin and nor- epinephrine. Furthermore, the monoaminergic systems are extensively distributed throughout the network of limbic, striatal, and prefrontal cortical neuronal circuits thought to support the behavioral and visceral manifes- tations of mood disorders. Increasing numbers of neu- roimaging, neuropathological, and biochemical studies indicate impairments in cellular plasticity and resilience in patients who suffer from severe, recurrent mood dis- orders. In this paper, we describe studies identifying pos- sible structural, functional, and cellular abnormalities associated with depressive disorders, which are poten- tially the cellular underpinnings of these diseases. We suggest that drugs designed to enhance cellular plastic- ity and resilience, and attenuate the activity of mal- adaptive stress-responsive systems, may be useful for the treatment of severe mood disorders.    © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:217-225.