Hippocampal morphology in lithium and non‐lithium‐treated bipolar I disorder patients, non‐bipolar co‐twins, and control twins

Abstract

Bipolar I disorder is a highly heritable psychiatric illness with undetermined predisposing genetic and environmental risk factors. We examined familial contributions to hippocampal morphology in bipolar disorder, using a population-based twin cohort design. We acquired high-resolution brain MRI scans from 18 adult patients with bipolar I disorder [BPI; mean age 45.6 ± 8.69 (SD); 10 lithium-treated], 14 non-bipolar co-twins, and 32 demographically matched healthy comparison twins. We used three-dimensional radial distance mapping techniques to visualize hippocampal shape differences between groups. Lithium-treated BPI patients had significantly larger global hippocampal volume compared to both healthy controls (9%) and non-bipolar co-twins (12%), and trend-level larger volumes relative to non-lithium-treated BPI patients (8%). In contrast, hippocampal volumes in non-lithium-treated BPI patients did not differ from those of non-bipolar co-twins and control twins. 3D surface maps revealed thicker hippocampi in lithium-treated BPI probands compared with control twins across the entire anterior-to-posterior extent of the cornu ammonis (CA1 and 2) regions, and the anterior part of the subiculum. Unexpectedly, co-twins also showed significantly thicker hippocampi compared with control twins in regions that partially overlapped those showing effects in the lithium treated BPI probands. These findings suggest that regionally thickened hippocampi in bipolar I disorder may be partly due to familial factors and partly due to lithium-induced neurotrophy, neurogenesis, or neuroprotection. Unlike schizophrenia, hippocampal alterations in co-twins of bipolar I disorder probands are likely to manifest as subtle volume excess rather than deficit, perhaps indicating protective rather than risk effects.