Evidence From Imaging Resilience Genetics for a Protective Mechanism Against Schizophrenia in the Ventral Visual Pathway

• Published in: Schizophrenia bulletin 2022-05, Vol.48 (3), p.551-562
• Main Authors: Hettwer, Meike D, Lancaster, Thomas M, Raspor, Eva, Hahn, Peter K, Mota, Nina Roth, Singer, Wolf, Reif, Andreas, Linden, David E J, Bittner, Robert A
• Format: Article
• Language: English
• Subjects: Brain - metabolism; Humans; Magnetic Resonance Imaging; Multifactorial Inheritance; Regular; Schizophrenia - diagnostic imaging; Schizophrenia - genetics; Schizophrenia - metabolism; Visual Pathways - diagnostic imaging; Visual Pathways - pathology
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbab151

Abstract Introduction Illuminating neurobiological mechanisms underlying the protective effect of recently discovered common genetic resilience variants for schizophrenia is crucial for more effective prevention efforts. Current models implicate adaptive neuroplastic changes in the visual system and their pro-cognitive effects as a schizophrenia resilience mechanism. We investigated whether common genetic resilience variants might affect brain structure in similar neural circuits. Method Using structural magnetic resonance imaging, we measured the impact of an established schizophrenia polygenic resilience score (PRSResilience) on cortical volume, thickness, and surface area in 101 healthy subjects and in a replication sample of 33 224 healthy subjects (UK Biobank). Finding We observed a significant positive whole-brain correlation between PRSResilience and cortical volume in the right fusiform gyrus (FFG) (r = 0.35; P = .0004). Post-hoc analyses in this cluster revealed an impact of PRSResilience on cortical surface area. The replication sample showed a positive correlation between PRSResilience and global cortical volume and surface area in the left FFG. Conclusion Our findings represent the first evidence of a neurobiological correlate of a genetic resilience factor for schizophrenia. They support the view that schizophrenia resilience emerges from strengthening neural circuits in the ventral visual pathway and an increased capacity for the disambiguation of social and nonsocial visual information. This may aid psychosocial functioning, ameliorate the detrimental effects of subtle perceptual and cognitive disturbances in at-risk individuals, and facilitate coping with the cognitive and psychosocial consequences of stressors. Our results thus provide a novel link between visual cognition, the vulnerability-stress concept, and schizophrenia resilience models.