Schizophrenia has been hypothesized to be a human-specific condition, but experimental approaches to testing this idea have been limited. Because Neanderthals, our closest evolutionary relatives, interbred with modern humans prior to their disappearance from the fossil record, leaving a residual echo that survives in our DNA today, we leveraged new discoveries about ancient hominid DNA to explore this hypothesis in living people in three converging ways. First, in four independent case–control datasets totaling 9,362 individuals, individuals with schizophrenia had less Neanderthal-derived genetic variation than controls (p = .044). Second, in 49 unmedicated inpatients with schizophrenia, having more Neanderthal admixture predicted less severe positive symptoms (p = .046). Finally, using ¹⁸F-fluorodopa PET scanning in 172 healthy individuals, having greater Neanderthal introgression was significantly associated with lower dopamine synthesis capacity in the striatum and pons (p's < 2 × 10⁻⁵), which is fundamentally important in the pathophysiology and treatment of psychosis. These results may help to elucidate the evolutionary history of a devastating neuropsychiatric disease by supporting the notion of schizophrenia as a human-specific condition. Additionally, the relationship between Neanderthal admixture and dopamine function suggests a potential mechanism whereby Neanderthal admixture may have affected our gene pool to alter schizophrenia risk and/or course.

中文翻译：

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活人中源自尼安德特人的遗传变异与精神分裂症诊断、精神病症状严重程度和多巴胺合成有关

精神分裂症被假设为人类特有的疾病，但测试这一想法的实验方法受到限制。因为尼安德特人，我们最接近的进化亲属，在现代人类从化石记录中消失之前与他们杂交，留下了今天在我们的 DNA 中幸存下来的残余回声，我们利用关于古代原始人 DNA 的新发现，在三个融合的活人身上探索了这一假设方法。首先，在总共 9,362 名个体的四个独立病例对照数据集中，与对照组相比，精神分裂症患者的尼安德特人遗传变异更少（p  = .044）。其次，在 49 名未接受药物治疗的精神分裂症住院患者中，尼安德特人混合物越多，阳性症状越不严重（p = .046)。最后，在 172 名健康个体中使用¹⁸ F-氟多巴 PET 扫描，具有较大的尼安德特人基因渗入与纹状体和脑桥中较低的多巴胺合成能力显着相关（p < 2 × 10 ^-5），这在病理生理学中非常重要和治疗精神病。这些结果可能有助于通过支持精神分裂症作为人类特定疾病的概念来阐明破坏性神经精神疾病的进化史。此外，尼安德特人混合物与多巴胺功能之间的关系表明了一种潜在的机制，即尼安德特人混合物可能影响我们的基因库以改变精神分裂症的风险和/或病程。