Vol 6 n° 2 - Neuroplasticity
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he recent development of neuroimaging tech- nologies  that  permit  in  vivo  characterization  of  the anatomical, physiological, and receptor pharmacological correlates of mood disorders have enabled significant advances toward delineating the neurobiological corre- lates of mood disorders. Because these conditions were not associated with gross brain pathology or with clear animal models for spontaneous, recurrent mood episodes, the availability of tools allowing noninvasive assessment of the human brain proved critical to illuminating the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). The results of studies apply- ing imaging technologies and postmortem studies have 1 9 9 C l i n i c a l   r e s e a r c h T Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Neuroplasticity in mood disorders Wayne C. Drevets, MD Keywords:  major  depressive  disorder;  bipolar  disorder;  neuroplasticity;  neuroimaging abnormalities; postmortem studies Author  affiliations:  Wayne  C.  Drevets,  MD,  Mood  and  Anxiety  Disorders Program, NIH NIMH/MIB, 15K North Dr, Bethesda, Md, USA Address  for  correspondence:  Wayne  C.  Drevets,  MD,  Mood  and  Anxiety Disorders  Program,  NIH  NIMH/MIB,  15K  North  Dr,  MSC  2670,  Bethesda,  MD 20892-2670, USA (e-mail: drevetsw@intra.nimh.nih.gov) Neuroimaging and neuropathological studies of major depressive disorder (MDD) and bipolar disorder (BD) have iden- tified abnormalities of brain structure in areas of the prefrontal cortex, amygdala, striatum, hippocampus, parahip- pocampal gyrus, and raphe nucleus. These structural imaging abnormalities persist across illness episodes, and prelimi- nary evidence suggests they may in some cases arise prior to the onset of depressive episodes in subjects at high familial risk for MDD. In other cases, the magnitude of abnormality is reportedly correlated with time spent depressed. Postmortem histopathological studies of these regions have shown abnormal reductions of synaptic markers and glial cells, and, in rare cases, reductions in neurons in MDD and BD. Many of the regions affected by these structural abnor- malities show increased glucose metabolism during depressive episodes. Because the glucose metabolic signal is domi- nated by glutamatergic transmission, these data support other evidence that excitatory amino acid transmission is ele- vated in limbic-cortical-striatal-pallidal-thalamic circuits during depression. Some of the subject samples in which these metabolic abnormalities have been demonstrated were also shown to manifest abnormally elevated stressed plasma cor- tisol levels. The co-occurrence of increased glutamatergic transmission and cortisol hypersecretion raises the possibility that the gray matter volumetric reductions in these depressed subjects are partly accounted for by processes homologous to the dendritic atrophy induced by chronic stress in adult rodents, which depends upon interactions between elevated glucocorticoid secretion and N-methyl-D-aspartate (NMDA)–glutamate receptor stimulation. Some mood-stabilizing and antidepressant drugs that exert neurotrophic effects in rodents appear to reverse or attenuate the gray matter volume abnormalities in humans with mood disorders. These neurotrophic effects may be integrally related to the therapeutic effects of such agents, because the regions affected by structural abnormalities in mood disorders are known to play major roles in modulating the endocrine, autonomic, behavioral, and emotional experiential responses to stressors.   © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:199-216.