The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

中文翻译：

---

危险因素对精神病发病和结局的影响：我们从 GAP 研究中学到的东西

在伦敦南部进行的 GAP 多学科研究，招募了 410 名首发精神病患者和 370 名对照；目的是阐明影响精神病发作和结果的多种遗传和环境因素。该研究表明，童年时期的逆境（尤其是失去父母、虐待和欺凌）会增加精神病发作的风险，尤其是阳性症状。来自少数民族的不良生活事件更接近发病，大麻使用也发挥了重要作用；事实上，四分之一的新精神病病例可归因于使用高效大麻。“急于下结论”的偏见似乎调节了低智商对精神病易感性的影响。我们确认环境因素在多基因风险的背景下起作用，并且遗传和环境共同作用，将个体推向表现出临床疾病的门槛。该研究证明了参与压力反应（HPA 轴和免疫系统）的生物学途径如何提供将社会风险因素与精神病症状发展联系起来的重要机制。暗示免疫/炎症成分与精神病有关的进一步证据来自我们在 FEP 中发现补体失调。患者还表现出抗微生物α-防御素的上调，以及参与 NF-κB 信号传导和细胞因子产生的基因表达模式的差异。非洲裔不仅增加了发病的风险，而且也增加了病程的难度。