Impact of genetic variants on hippocampal volume among individuals with schizophrenia and bipolar disorders

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BACKGROUND AND HYPOTHESIS: Hippocampal volume reduction is a consistent finding in schizophrenia (SCZ) and bipolar disorder type I (BP-I), yet the role of genetic factors remains unclear. We investigated the influence of DISC1 (rs821616), AKT1 (rs1130233), COMT (rs4680), and GSK-3ꞵ(rs334558) polymorphisms on hippocampal morphology. STUDY DESIGN: Seventy-one participants (25 SCZ, 22 BP-I, 24 healthy controls, HC) underwent 1.5T MRI and genotyping. Bayesian multilevel models estimated associations between corrected hippocampal volume, diagnosis, hemisphere, and genetic variants. STUDY RESULTS: Both SCZ and BP-I showed significantly smaller hippocampal volumes compared with HC (Average Marginal Effects: SCZ vs HC = -1.38; BP-I vs HC = -1.46; probability of direction [PD] = 100%). Rightward asymmetry was preserved across groups. The COMT AA genotype was associated with lower hippocampal volume (AME = -0.67; PD = 99%), while DISC1 AT carriers showed moderate reductions (AME = -0.37; PD = 96%). GSK-3ꞵ contributed to variability but not mean volume, and AKT1 showed no clear effects. CONCLUSIONS: Hippocampal atrophy is a shared marker of SCZ and BP-I, with preserved lateralization. COMT and DISC1 variations appear to modulate hippocampal volume, supporting their role in psychosis vulnerability.

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