Evidence from imaging resilience genetics for a protective mechanism against schizophrenia in the ventral visual pathway

Abstract Recently, the first genetic variants conferring resilience to schizophrenia have been identified. However, the neurobiological mechanisms underlying their protective effect remain unknown. Current models implicate adaptive neuroplastic changes in the visual system and their pro-cognitive effects in schizophrenia resilience. Here, we test the hypothesis that comparable changes can emerge from schizophrenia resilience genes. To this end, we used structural magnetic resonance imaging to investigate the effects of a schizophrenia polygenic resilience score (PRSResilience) on cortical morphology (discovery sample: n=101; UK Biobank replication sample: n=33,224). We observed positive correlations between PRSResilience and cortical volume in the fusiform gyrus, a central hub within the ventral visual pathway. Our findings indicate that resilience to schizophrenia arises partly from genetically mediated enhancements of visual processing capacities for social and non-social object information. This implies an important role of visual information processing for mitigating schizophrenia risk, which might also be exploitable for early intervention studies.