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.

中文翻译：

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来自成像弹性遗传学的证据证明腹侧视觉通路中抗精神分裂症的保护机制

引言 阐明最近发现的常见精神分裂症遗传弹性变异的保护作用背后的神经生物学机制对于更有效的预防工作至关重要。目前的模型将视觉系统中的适应性神经可塑性变化及其促认知效应作为精神分裂症的恢复机制。我们研究了常见的遗传弹性变异是否会影响相似神经回路中的大脑结构。方法 使用结构磁共振成像，我们测量了已建立的精神分裂症多基因弹性评分 (PRSResilience) 对 101 名健康受试者和 33224 名健康受试者的复制样本 (UK Biobank) 的皮质体积、厚度和表面积的影响。我们观察到 PRSResilience 与右侧梭状回 (FFG) 皮质体积之间存在显着的全脑正相关性（r = 0.35；P = .0004）。该集群中的事后分析揭示了 PRSResilience 对皮质表面积的影响。复制样本显示 PRSResilience 与左侧 FFG 中的整体皮质体积和表面积呈正相关。结论 我们的研究结果代表了精神分裂症的遗传恢复因子的神经生物学相关性的第一个证据。他们支持这样一种观点，即精神分裂症的恢复力来自加强腹侧视觉通路中的神经回路以及增强的社会和非社会视觉信息消歧能力。这可能有助于社会心理功能，改善高危个体微妙的知觉和认知障碍的不利影响，并促进应对压力源的认知和社会心理后果。因此，我们的结果提供了视觉认知、脆弱性压力概念和精神分裂症复原力模型之间的新颖联系。