Vincenzo Matteo Di, Prachason Thanavadee, Sampogna Gaia, Arias-Magnasco Angelo, Danae Lin Bochao, Pries Lotta-Katrin, van Os Jim, Rutten Bart P F, Barzilay Ran, Fiorillo Andrea, Guloksuz Sinan
Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy.
Department of Psychiatry, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
medRxiv. 2024 Nov 11:2024.11.11.24316985. doi: 10.1101/2024.11.11.24316985.
To assess the longitudinal associations of genomic and exposomic liabilities for schizophrenia, both independently and jointly, with distressing psychotic experiences (PEs) and their persistence in early adolescence. The Adolescent Brain and Cognitive Development Study data from children with European ancestry were used (n=5,122). The primary outcome was past-month distressing PEs at 3-year follow-up. Secondary outcomes were lifetime distressing PEs defined at varying cutoffs of persistence (from ≥ 1-4 waves). Multilevel logistic regression models were used to test the independent and joint associations of the binary modes (risk-category defined as above 75th percentile) of polygenic risk score for schizophrenia (PRS-SCZ) and exposome score for schizophrenia (ES-SCZ) on the outcomes. The relative excess risk due to interaction (RERI) was determined using the delta method to indicate departure additive interaction. PRS-SCZ was statistically significantly associated with lifetime distressing PEs (≥ 1 wave) (OR 1.29 [95% CI 1.08, 1.53]) and repeating distressing PEs ≥ 2 waves (OR 1.34 [95% CI 1.08, 1.65]) but not with past-month distressing PEs or repeating distressing PEs at a higher cutoff of persistence. ES-SCZ was consistently associated with past-month and repeating distressing PEs at all cutoffs, with increasing strength of association as a function of PEs persistence (one wave: OR 2.77 [95% CI 2.31, 3.31]; two waves: OR 3.16 [95% CI 2.54, 3.93]; three waves: OR 3.93 [95% CI 2.86, 5.40]; four waves: OR 3.65 [95% CI 2.34, 5.70]). There was evidence for additive interaction between ES-SCZ and PRS-SCZ for lifetime distressing PEs (RERI=1.26 95%CI: 0.14, 2.38), and repeating distressing PEs ≥ 2 waves (RERI=1.79, 95%CI: 0.35, 3.23). Genomic and exposomic liabilities for schizophrenia were independently and jointly associated with distressing PEs, as well as their persistence in early adolescence.
为了评估精神分裂症的基因组和暴露组易感性与痛苦的精神病性体验（PEs）及其在青春期早期的持续性之间的纵向关联，包括独立关联和联合关联。使用了来自欧洲血统儿童的青少年大脑与认知发展研究数据（n = 5122）。主要结局是3年随访时过去一个月的痛苦PEs。次要结局是根据不同持续时间阈值（从≥1 - 4次发作）定义的终生痛苦PEs。使用多级逻辑回归模型来检验精神分裂症多基因风险评分（PRS - SCZ）和精神分裂症暴露组评分（ES - SCZ）的二元模式（风险类别定义为高于第75百分位数）与结局之间的独立和联合关联。使用delta方法确定交互作用导致的相对超额风险（RERI），以表明偏离相加交互作用。PRS - SCZ与终生痛苦PEs（≥1次发作）（比值比1.29 [95%置信区间1.08, 1.53]）和重复痛苦PEs≥2次发作（比值比1.34 [95%置信区间1.08, 1.65]）在统计学上显著相关，但与过去一个月的痛苦PEs或更高持续时间阈值下的重复痛苦PEs无关。ES - SCZ在所有阈值下均与过去一个月和重复痛苦PEs持续相关，且随着PEs持续时间的增加关联强度增加（一次发作：比值比2.77 [95%置信区间2.31, 3.31]；两次发作：比值比3.16 [95%置信区间2.54, 3.93]；三次发作：比值比3.93 [95%置信区间2.86, 5.40]；四次发作：比值比3.65 [95%置信区间2.34, 5.70]）。有证据表明ES - SCZ和PRS - SCZ之间存在相加交互作用，对于终生痛苦PEs（RERI = 1.26，95%置信区间：0.14, 2.38）以及重复痛苦PEs≥2次发作（RERI = 1.79，95%置信区间：0.35, 3.23）。精神分裂症的基因组和暴露组易感性与痛苦的PEs及其在青春期早期的持续性独立且联合相关。
