Hajek T, Kopecek M, Hoschl C, Alda M. Reduced hippocampal volumes in bipolar disorders are masked by exposure to lithium - meta-analysis. P-16-008, 28th CINP World Congress of Neuropsychopharmacology. Stockholm, 3-7 June 2012

6. 6. 2012

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 bipolar patients may reflect putative neuroprotective effects of lithium (Li).

To investigate hippocampal volumes in bipolar disorders (BD) while controlling for Li exposure, we performed a meta-analysis of neuroimaging studies which subdivided BD patients based on the presence or absence of current Li treatment. Hippocampal volumes were compared by combining standardized differences in means (Cohen`s d) from individual studies using random effect models.

Overall, we meta-analyzed data from 101 Li treated BD subjects, 245 BD subjects not treated with Li (non-Li group) and 456 controls from 16 studies. Both the left and right hippocampal volumes were significantly larger in the Li treated BD subjects than in controls (Cohen’s d=0.53, 95% CI=0.18; 0.88; Cohen’s d=0.51; 95% CI=0.21; 0.81, respectively) or the non-Li group (Cohen’s d=0.93; 95% CI=0.56; 1.31; Cohen’s d=1.07, 95% CI=0.70; 1.45, respectively), which had smaller bilateral hippocampal volumes than the controls (Cohen’s d=-0.36, 95% CI=-0.55; -0.17; Cohen’s d=-0.38; 95% CI=-0.63; -0.13, for the left and right hippocampal volumes respectively). There was no evidence of publication bias.

Considering the opposite direction of findings in subjects with versus without exposure to Li, the preserved hippocampal volumes among BD subjects in the majority of individual studies and all previous meta-analyses, were most likely related to the inclusion of Li-treated subjects. Our findings provide indirect support for the neuroprotective effects of Li and for the negative effects of bipolar disorders on hippocampal volumes.