The role of hippocampus in the pathophysiology of bipolar disorder

Bipolar disorder (BD) is thought to be associated with abnormalities within discrete brain regions associated with emotional regulation, particularly in fronto-limbic-subcortical circuits. Several reviews have addressed the involvement of the prefrontal cortex in the pathophysiology of BD, whereas little attention has been given to the role of the hippocampus. This study critically reviews data from brain imaging, postmortem, neuropsychological, and preclinical studies, which suggested hippocampal abnormalities in BD. Most of the structural brain imaging studies did not find changes in hippocampal volume in BD, although a few studies suggested that anatomical changes might be restricted to the psychotic, pediatric, or unmedicated BD subgroups. Functional imaging studies showed abnormal brain activation in the hippocampus and its closely related regions during emotional, attentional, and memory tasks. This is consistent with neuropsychological findings that revealed a wide range of cognitive disturbances during acute mood episodes and a significant impairment in declarative memory during remission. Postmortem studies indicate abnormal glutamate and GABA transmission in the hippocampus of BD patients, whereas data from preclinical studies suggest that the regulation of hippocampal plasticity and survival might be associated with the therapeutic effects of mood stabilizers. In conclusion, the available evidence suggests that the hippocampus plays an important role in the pathophysiology of BD.