Abstract

Mood disorders are related to considerable morbidity and mortality, and although there is little doubt that they are brain-based disorders, their neural correlates still remain elusive. A neuro-anatomic model of mood regulation comprising the prefrontal cortex, amygdala-hippocampus complex, thalamus, basal ganglia, and connections among these areas has been proposed. We reviewed the evidence for regional brain abnormalities in bipolar disorder, and attempted to integrate available findings into a comprehensive pathophysiological model of illness. A computerized Medline Ovid search was conducted for the period 1966-2002, and complemented by a manual search of bibliographical references from recent reviews. Articles meeting specified criteria were included. Hyperintense lesions in cortical and subcortical regions are the most consistently reported and widely studied structural abnormalities. Smaller prefrontal cortical volume is a common finding in bipolar disorder and unipolar depression. Enlarged amygdala (in bipolar disorder) and smaller hippocampus (in unipolar depression) have been reported by several groups. Decreased volumes (in unipolar depression) and increased or unaltered volumes (in bipolar disorder) of striatal structures have been reported. Bipolar and unipolar mood disorders are associated with detectable structural brain abnormalities. The histopathology underlying such anatomical changes remains to be elucidated. To reach more definitive conclusions about neuroanatomical changes that take place during the course of mood disorders, prospective longitudinal studies are needed. Also, integration with functional imaging is necessary in order to elucidate the relevance of identified structural abnormalities.

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