New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings.

Bipolar affective disorder (BD) is a severe mental illness, characterized by episodes of mania and depression. With the development of Magnetic Resonance Imaging (MRI), neuroimaging methods are now allowing investigation of the neurocircuitry involved in this disorder. This in turn has aided further neuropathological exploration of the brain. Structural MRI and Magnetic Resonance Spectroscopy studies suggest that brain abnormalities in BD are mostly regional, as global measures (cerebral, white and gray matter and ventricular volumes) do not seem to be affected in the majority of patients. The prefrontal and anterior cingulate cortices, and amygdalae are consistently implicated in BD, whilst the evidence for hippocampal involvement is less convincing. Functional studies have found that the activity of the dorsal prefrontal cortex and the anterior cingulate are closely associated with mood symptoms. Activity in the ventral and orbital prefrontal cortex appears reduced both during episodes and in remission. In contrast, amygdala activity shows a persistent increase. We suggest that abnormal interaction between the amygdala and the ventral/orbitofrontal cortex may be a central feature of the pathophysiology of BD.