Objective: Although a heritable contribution to risk for major depressive disorder (MDD) has been established and neural alterations in patients have been identified through neuroimaging, it is unclear which brain abnormalities are related to genetic risk. Studies on brain structure of high-risk subjects - such as individuals carrying a familial liability for the development of MDD - can provide information on the potential usefulness of these measures as intermediate phenotypes of MDD.
Methods: 63 healthy first-degree relatives of patients with MDD and 63 healthy controls underwent structural magnetic resonance imaging. Regional gray matter volumes were analyzed via voxel-based morphometry (VBM).
Results: Whole-brain analysis revealed significantly larger gray matter volume in the bilateral amygdala in first-degree relatives of patients with MDD. Furthermore, relatives showed significantly larger gray matter volume in anatomical structures found relevant to MDD in previous literature, specifically in the bilateral hippocampus and amygdala as well as the left dorsolateral prefrontal cortex (DLPFC). Bilateral DLPFC volume correlated positively with the experience of negative affect.
Conclusions: Larger gray matter volume in healthy relatives of MDD patients point to a possible vulnerability mechanism in MDD etiology and therefore extend knowledge in the field of high-risk approaches in MDD.
Keywords: Amygdala; Gray matter volume; High-risk; Major depressive disorder; voxel-based morphometry.