Smaller hippocampal volumes relative to controls are among the most replicated neuroimaging findings in individuals with unipolar but not bipolar depression. Preserved hippocampal volumes in most studies of participants with bipolar disorder may reflect potential neuroprotective effects of lithium (Li).
Methods: To investigate hippocampal volumes in patients with bipolar disorder while controlling for Li exposure, we performed a meta-analysis of neuroimaging studies that subdivided patients based on the presence or absence of current Li treatment. To achieve the best coverage of literature, we categorized studies based on whether all or a majority, or whether no or a minority of patients were treated with Li.
Hippocampal volumes were compared by combining standardized differences between means (Cohen d) from individual studies using random-effects models. Conclusion: When expos ure to Li was minimized, patients with bipolar disorder showed smaller hippocampal volumes than controls or Li-treated patients.
Our findings provide indirect support for the negative effects of bipolar disorder on hippocampal volumes and are consist ent with the putative neuroprotective effects of Li. The preserved hippocampal volumes among patients with bipolar disorder in most individual studies and all previous meta-analyses may have been related to the inclusion of Li-treated participants