Hippocampal volume changes in healthy subjects at risk of unipolar depression

Unipolar depression is moderately heritable. It is unclear whether structural brain changes associated with unipolar depression are present in healthy persons at risk of the disorder. Here we investigated whether a genetic predisposition to unipolar depression is associated with structural brain changes. A priori, hippocampal volume reductions were hypothesized. Using a high-risk study design, magnetic resonance imaging brain scans were obtained from 59 healthy high-risk subjects having a co-twin with unipolar depression, and 53 healthy low-risk subjects without a first-degree family history of major psychiatric disorder. High-risk twins had smaller hippocampal volumes than low-risk twins (p < 0.04). The finding was most pronounced in DZ twins. Groups did not differ on global brain tissue volumes or regional tissue volumes assessed in exploratory voxel-wise whole cerebrum analyses. In conclusion, hippocampal volume reduction may index a predisposition to develop depression and thus may be predictive of future onset of the disorder. Further studies are needed to elucidate the role of (shared) environmental and genetic factors.