Smaller hippocampal volumes are among the most replicated neuro imaging findings in patients with major depressive disorder compared with healthy controls.The excitotoxicity is considered to be the reason for this.Though clinical features and excitotoxic changes are probably similar, in bipolar patients, all published meta analysis found the hippocampal volume to be preserved. What could be the reason for this?
Hajeke et al from Dalhousie University investigates the possibility that hippocampal volume changes in patients with bipolar disorder are masked by exposure to neuroprotective effects of Li ie Lithium might be protecting the hippocampus from shrinking in these patients.They did a systematic review of all published literature up to 2011, investigating hippocampal volumes in bipolar patients where data on Lithium exposure was also available.
They performed 3 meta-analyses to investigate the differences in hippocampal volumes between 1) patients with bipolar disorder, most or all of whom were treated with Li (Li group), and controls; 2) patients with bipolar disorder, most or all of whom were not currently treated with Li (non-Li group), and controls; and 3) Li-treated patients with bipolar disorder and patients who were not treated with Li at the time of scanning.Volumes of the left and right hippocampus was the primary outcome measure.From the 144 studies identified, 16 met all criteria and were included in the analysis.
Lithium vs Control groups: Both the left and right hippocampi were significantly larger in the Li than in the control groups.
Non-Lithium vs control Groups: Both the left and right hippocampi were significantly smaller in the non-Li than in the control group
Lithium versus non-Li groups: Both the left and right hippocampi were significantly larger in the Li-treated patients with bipolar disorder than in the non- Li group.
Summary of findings:
This team found significantly smaller bilateral hippocampal volumes in patients with bipolar disorder who were currently not treated with Li relative to healthy controls or Li-treated patients with bipolar disorder, who had significantly larger hippocampal volumes than the controls.This study challenges the prevailing notion that hippocampus is preserved in bipolar disorder. It supports the argument that Lithium might be protecting the hippocampus from shrinking in bipolar patients.
A recent mega-analysis summarized individual data from 5 previous studies and found significantly larger hippocampal volumes in Li-treated patients with bipolar disorder than in those who were not treated with Li or healthy controls (Hallahan B, Newell J, Soares JC, et al. Structural magnetic resonance imaging in bipolar disorder: an international collaborative mega-analysis of individual adult patient data. Biol Psychiatry 2011;69:326-35)
1.To achieve the best coverage of the available literature, the studies in which the majority of patients was treated with Li were analyzed together with the studies where all patients were treated with Li. Similarly, the studies in which the minority of patients was treated with Li were analyzed together with the studies where no patient was treated with Li.
2. Several potential clinical confounders were not well controlled for in the analyzed studies. It was unclear whether or not the patients were compliant, were treated with a sufficient dose of Li for a sufficient duration of time or whether the clinical groups were comparable in illness burden.
Conclusion: Authors conclude that this analysis provide indirect support for the negative effects of bipolar disorder on hippocampal volumes and are consistent with the hypothesis that Li may have neuroprotective effects.
Summary of the article:
Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis. Hajek T, Kopecek M, Höschl C, Alda M. J Psychiatry Neurosci. 2012 Sep;37(5):333-43