Rodriguez Victoria, Alameda Luis, Aas Monica, Gayer-Anderson Charlotte, Trotta Giulia, Spinazzola Edoardo, Quattrone Diego, Tripoli Giada, Jongsma Hannah E, Stilo Simona, La Cascia Caterina, Ferraro Laura, La Barbera Daniele, Lasalvia Antonio, Tosato Sarah, Tarricone Ilaria, Bonora Elena, Jamain Stéphane, Selten Jean-Paul, Velthorst Eva, de Haan Lieuwe, Llorca Pierre-Michel, Arrojo Manuel, Bobes Julio, Bernardo Miguel, Arango Celso, Kirkbride James, Jones Peter B, Rutten Bart P, Richards Alexander, Sham Pak C, O'Donovan Michael, Van Os Jim, Morgan Craig, Di Forti Marta, Murray Robin M, Vassos Evangelos
Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College of London, London SE5 8AB, United Kingdom.
North London NHS Foundation Trust, Camden Early Intervention Service London, London NW1 0AS, United Kingdom.
Schizophr Bull. 2024 Dec 10. doi: 10.1093/schbul/sbae207.
Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified.
We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry. Firstly, we tested whether the association of polygenic risk scores for schizophrenia, bipolar disorder, and depression (PRS-SZ, PRS-BD, and PRS-D) with schizophrenia-spectrum disorder and affective psychosis differed when participants were stratified by exposure to specific environmental factors. Secondly, regression models including each PRS and polyenvironmental measures, including migration, paternal age, childhood adversity and frequent cannabis use, were run to test potential polygenic by polyenvironment interactions.
In schizophrenia-spectrum disorder vs controls comparison, PRS-SZ was the strongest genetic predictor, having a nominally larger effect in nonexposed to strong environmental factors such as frequent cannabis use (unexposed vs exposed OR 2.43 and 1.35, respectively) and childhood adversity (3.04 vs 1.74). In affective psychosis vs controls, the relative contribution of PRS-D appeared to be stronger in those exposed to environmental risk. No evidence of interaction was found between any PRS with polyenvironmental score.
Our study supports an independent role of genetic liability and polyenvironmental risk for psychosis, consistent with the liability threshold model. Whereas schizophrenia-spectrum disorders seem to be mostly associated with polygenic risk for schizophrenia, having an additive effect with well-replicated environmental factors, affective psychosis seems to be a product of cumulative environmental insults alongside a higher genetic liability for affective disorders.
多种遗传和环境风险因素在精神分裂症谱系障碍和情感性精神病的发生发展中起作用。它们如何共同作用尚待阐明。
我们分析了573例欧洲血统的首发精神病病例和1005例对照。首先，我们测试了在根据特定环境因素暴露情况对参与者进行分层时，精神分裂症、双相情感障碍和抑郁症的多基因风险评分（PRS-SZ、PRS-BD和PRS-D）与精神分裂症谱系障碍和情感性精神病之间的关联是否不同。其次，运行包括每个PRS和多环境测量指标（包括移民、父亲年龄、童年逆境和频繁使用大麻）的回归模型，以测试多基因与多环境之间的潜在相互作用。
在精神分裂症谱系障碍与对照的比较中，PRS-SZ是最强的遗传预测因子，在未暴露于频繁使用大麻（未暴露组与暴露组的比值比分别为2.43和1.35）和童年逆境（3.04与1.74）等强烈环境因素的人群中，其名义效应更大。在情感性精神病与对照的比较中，PRS-D在暴露于环境风险的人群中的相对贡献似乎更强。未发现任何PRS与多环境评分之间存在相互作用的证据。
我们的研究支持遗传易感性和多环境风险在精神病中的独立作用，这与易感性阈值模型一致。精神分裂症谱系障碍似乎主要与精神分裂症的多基因风险相关，与已充分证实的环境因素具有累加效应，而情感性精神病似乎是累积环境损伤与情感障碍更高遗传易感性共同作用的产物。
