Neurophysiology of Bipolar Disorder

Functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) studies provide an exciting opportunity to understand the neural substrates that underlie the pathophysiology of bipolar disorder. This chapter reviews fMRI and MRS meta-analyses from the past 10 years to examine whether meta-analytic results differ from those otherwise expected on the basis of individual studies considered in isolation. Across different meta-analytic studies, and predominantly consistent with extant fMRI hypotheses, the most replicated findings are an overactivity of amygdala, especially during emotional processing, and underactivity of right ventrolateral prefrontal cortex during emotional or cognitive processing in bipolar disorder. These functional abnormalities appear to present during mania or depression, but not during euthymia, suggesting they are related to mood state, symptom severity, or both. Additionally, they appear to be rather specific to bipolar disorder, as opposed to major depressive disorder or schizophrenia. Recent prospective studies also suggest that clinical improvement associates with normalization of functional abnormalities or functional connectivity between prefrontal cortex and amygdala. MRS meta-analyses, although more limited than fMRI, suggest elevated glutamate in prefrontal cortex and decreased N-acetylaspartate in the basal ganglia and hippocampus. Additional studies employing multimodal imaging or longitudinal designs could help to advance the understanding of these neurofunctional and neurochemical brain abnormalities and to develop better preventive and therapeutic strategies for this condition.