Importance Genetic risk factors are known to play a role in the etiology of psychotic experiences in the general population. Little is known about whether these risk factors interact with environmental risks for psychotic experiences. Objective To assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design. Design, Setting, and Participants This twin study, conducted from December 1, 2014, to August 31, 2020, included a UK-based sample of twin pairs aged 16 years. This investigation evaluated the extent to which the genetic variance underlying psychotic experiences and the magnitude of the heritability of psychotic experiences was moderated by exposure to 5 environmental risk factors (bullying, dependent life events, cannabis use, tobacco use, and low birth weight). Psychotic experiences were assessed by 5 self-reported measures and 1 parent-reported measure. Participants' exposure to environmental risks was assessed at birth and age 12 to 16 years. Structural equation models were used to assess differences in the variance in and heritability of psychotic experiences across these exposures, while controlling for gene-environment correlation effects. Analyses were repeated in an independent Swedish sample. Data analyses were performed from September 1, 2018, to August 31, 2020. Main Outcomes and Measures Primary outcome measures were exposure to environmental factors, as measured by a composite score, and psychotic experiences. Results A total of 4855 twin pairs (1926 female same-sex pairs, 1397 male same-sex pairs, and 1532 opposite-sex pairs) were included from the Twins Early Development Study (TEDS), and 6435 twin pairs (2358 female same-sex pairs, 1861 male same-sex pairs, and 2216 opposite-sex pairs) were included from the Child and Adolescent Twin Study in Sweden (CATSS). Mean age of twins from TEDS was 16.5 years. Mean age of twins from CATSS was 18.6 years. More exposure to environmental risk factors was associated with having more psychotic experiences. The relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia (44%; 95% CI, 33%-53% to 38%; 95% CI, 14%-58%), cognitive disorganization (47%; 95% CI, 38%-51% to 32%; 95% CI, 11%-45%), grandiosity (41%; 95% CI, 29%-52% to 32%; 95% CI, 9%-48%), and anhedonia (49%; 95% CI, 42%-53% to 37%; 95% CI, 15%-54%). This pattern was replicated for the measure of psychotic experiences in the independent Swedish replication sample. The heritability of hallucinations and parent-rated negative symptoms remained relatively constant. Conclusions and Relevance Findings of this twin study suggest that environmental factors play a greater role in the etiology of psychotic experiences than genetic factors. The relative importance of environmental factors is even higher among individuals exposed to environmental risks for psychotic experiences, highlighting the importance of a diathesis-stress or bioecological framework for understanding adolescent psychotic experiences.

中文翻译：

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青少年精神病经历的遗传性和与环境风险的相互作用。

重要性 已知遗传风险因素在普通人群的精神病经历的病因学中发挥作用。关于这些风险因素是否与精神病经历的环境风险相互作用，我们知之甚少。目的使用双胞胎设计评估与青春期精神病经历相关的病因异质性和环境风险暴露。设计、设置和参与者 这项双胞胎研究于 2014 年 12 月 1 日至 2020 年 8 月 31 日进行，包括英国的 16 岁双胞胎样本。这项调查评估了精神病经历背后的遗传变异程度和精神病经历的遗传力大小受到 5 种环境风险因素（欺凌、依赖生活事件、大麻使用、烟草使用、和低出生体重）。精神病经历通过 5 项自我报告的措施和 1 项家长报告的措施进行评估。参与者在出生时和 12 至 16 岁时对环境风险的暴露程度进行了评估。结构方程模型用于评估这些暴露中精神病经历的方差和遗传力的差异，同时控制基因-环境相关效应。在一个独立的瑞典样本中重复分析。数据分析于 2018 年 9 月 1 日至 2020 年 8 月 31 日进行。主要结果和措施 主要结果措施是通过综合评分衡量的环境因素暴露和精神病经历。结果共4855对双胞胎（女性同性对1926对，男性同性对1397对，双胞胎早期发育研究 (TEDS) 包括 6435 对双胞胎（2358 对女性同性对、1861 对男性同性对和 2216 对异性对）来自儿童和瑞典青少年双胞胎研究 (CATSS)。TEDS 双胞胎的平均年龄为 16.5 岁。CATSS 双胞胎的平均年龄为 18.6 岁。更多地暴露于环境风险因素与更多的精神病经历有关。随着偏执狂的环境暴露增加（44%；95% CI，33%-53% 至 38%；95% CI，14%-58%）、认知紊乱（47% ; 95% CI, 38%-51% 至 32%; 95% CI, 11%-45%), 浮夸 (41%; 95% CI, 29%-52% 至 32%; 95% CI, 9%- 48%）和快感缺失（49%；95% CI，42%-53% 至 37%；95% CI，15%-54%）。这种模式被复制用于在独立的瑞典复制样本中测量精神病经历。幻觉和父母评定的阴性症状的遗传率保持相对恒定。结论和相关性这项双胞胎研究的结果表明，环境因素在精神病经历的病因学中比遗传因素发挥更大的作用。在暴露于精神病经历的环境风险的个体中，环境因素的相对重要性甚至更高，突出了素质压力或生物生态框架对于理解青少年精神病经历的重要性。结论和相关性这项双胞胎研究的结果表明，环境因素在精神病经历的病因学中比遗传因素发挥更大的作用。在暴露于精神病经历的环境风险的个体中，环境因素的相对重要性甚至更高，突出了素质压力或生物生态框架对于理解青少年精神病经历的重要性。结论和相关性这项双胞胎研究的结果表明，环境因素在精神病经历的病因学中比遗传因素发挥更大的作用。在暴露于精神病经历的环境风险的个体中，环境因素的相对重要性甚至更高，突出了素质压力或生物生态框架对于理解青少年精神病经历的重要性。