Social Genetic and Developmental Psychiatric Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
Schizophr Bull. 2023 Mar 15;49(2):319-328. doi: 10.1093/schbul/sbac149.
Large-scale epidemiological and genetic research have shown that psychotic experiences in the community are risk factors for adverse physical and psychiatric outcomes. We investigated the associations of six types of specific psychotic experiences and negative symptoms assessed in mid-adolescence with well-established environmental and genetic risk factors for psychosis.
Fourteen polygenic risk scores (PRS) and nine geographical environmental variables from 3590 participants of the Twins Early Development Study (mean age 16) were associated with paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and negative symptoms scales. The predictors were modeled using LASSO regularization separately (Genetic and Environmental models) and jointly (GE model).
In joint GE models, we found significant genetic associations of negative symptoms with educational attainment PRS (β = -.07; 95% CI = -0.12 to -0.04); cognitive disorganization with neuroticism PRS (β = .05; 95% CI = 0.03-0.08); paranoia with MDD (β = .07; 95% CI = 0.04-0.1), BMI (β = .05; 95% CI = 0.02-0.08), and neuroticism PRS (β = .05; 95% CI = 0.02-0.08). From the environmental measures only family SES (β = -.07, 95% CI = -0.10 to -0.03) and regional education levels (β = -.06; 95% CI = -0.09 to -0.02) were associated with negative symptoms.
Our findings advance understanding of how genetic propensity for psychiatric, cognitive, and anthropometric traits, as well as environmental factors, together play a role in creating vulnerability for specific psychotic experiences and negative symptoms in mid-adolescence.
大规模的流行病学和遗传学研究表明，社区中的精神病性体验是不良身体和精神结局的危险因素。我们研究了青少年中期评估的六种特定精神病性体验和阴性症状与精神病既定的环境和遗传风险因素的关联。
来自 3590 名双胞胎早期发育研究（平均年龄 16 岁）的 14 种多基因风险评分（PRS）和 9 种地理环境变量与妄想、幻觉、认知解体、夸大妄想、快感缺失和阴性症状量表相关。使用 LASSO 正则化分别（遗传和环境模型）和联合（GE 模型）对预测因子进行建模。
在联合 GE 模型中，我们发现阴性症状与教育程度 PRS（β=-.07；95%CI=-.12 至-.04）；认知解体与神经质 PRS（β=0.05；95%CI=0.03-0.08）；偏执与 MDD（β=0.07；95%CI=0.04-0.1），BMI（β=0.05；95%CI=0.02-0.08）和神经质 PRS（β=0.05；95%CI=0.02-0.08）存在显著的遗传关联。从环境测量来看，只有家庭 SES（β=-.07，95%CI=-.10 至-.03）和区域教育水平（β=-.06；95%CI=-.09 至-.02）与阴性症状相关。
我们的研究结果加深了对遗传倾向、认知和人体测量特征以及环境因素如何共同作用，导致青少年中期特定精神病性体验和阴性症状易感性的理解。
