Association between duration of lithium exposure and hippocampus/amygdala volumes in type I bipolar disorder

Background: Prior studies on the effects of lithium on limbic and subcortical gray matter volumes are mixed. It is possible that discrepant findings may be explained by the duration of lithium exposure. We investigated this issue in individuals with type I bipolar disorder (BP-I). Methods: Limbic and subcortical gray matter volume was measured using FreeSurfer in 60 subjects: 15 with BP-I without prior lithium exposure [no-exposure group (NE)]; 15 with BP-I and lithium exposure < 24 months [short-exposure group (SE)]; 15 with BP-I and lithium exposure > 24 months [long-exposure group (LE)]; and 15 healthy controls (HC). Results: No differences in limbic and subcortical gray matter volumes were found between LE and HC. Hippocampal and amygdalar volumes were larger bilaterally in both LE and HC when compared to NE. Amygdalar volumes were larger bilaterally in SE when compared to NE but did not differ from LE. Hippocampal volumes were smaller bilaterally in SE when compared to LE and HC but did not differ from NE. No between-group differences on subcortical gray matter or other limbic structure volumes were observed. Limitations: Cross-sectional design and concurrent treatment with other medications limit attribution of between-group differences to lithium exposure alone. Conclusions: The effect of lithium exposure on limbic and subcortical gray matter volumes appears to be time-dependent and relatively specific to the hippocampus and the amygdala, with short-term effects on the amygdala and long-term effects on both structures. These results support the clinical importance of long-term lithium treatment in BP-I.