Neuroimaging and neuropathological findings in bipolar disorder.
Bipolar disorder (BPD) is increasingly recognized as a neuropathological disorder characterized by reductions in grey matter (GM) volume, as measured by magnetic resonance imaging (MRI) and neuronal and postmortem glial cell changes. Here, we use an anatomical framework to discuss the neurobiology of BPD, focusing on individual components of the "visceromotor network" that regulates bodily homeostasis along with neurophysiological and neuroendocrine responses to stress. MRI-defined reductions in GM volume, combined with neuronal changes, are observed in the perigenual anterior cingulate cortex (ACC) of individuals with BPD, while postmortem glial cell loss is also a characteristic of Brodmann's Area 9. Both postmortem neuronal loss and reduced GM volume have been reported in the amygdala and hippocampus. These structural changes to components of the visceromotor network are associated with increased regional cerebral blood flow (rCBF) or blood oxygenated level-dependent (BOLD) activity in response to affective or rewarding stimuli, raising the possibility that the BPD-associated structural changes are secondary to a glutamate-driven excitotoxic process.