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.
Impact of genetic variants on hippocampal volume among individuals with schizophrenia and bipolar disorders
Trevisson, Eva;Olivo, Daniele;Sambataro, Fabio;
2026
Abstract
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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