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童年期虐待在遗传背景对年轻人精神分裂症风险的影响中起中介作用。

Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults.

机构信息

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi, 287 - 41125, Modena, Italy.

Department of Psychiatry, Brain Center University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.

出版信息

Transl Psychiatry. 2022 Jun 1;12(1):219. doi: 10.1038/s41398-022-01975-1.

Abstract

Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.

摘要

儿童虐待(CM)和遗传易感性都是精神病的风险因素,但它们之间的关系尚不完全清楚。本研究受最近发现的 CM 的遗传风险的启发,研究了精神分裂症遗传风险是否也会增加 CM 的风险,从而影响精神病风险的假设。在乌得勒支大麻队列(N=1262)和独立的 IMAGEN 队列(N=1740)的参与者中,研究了精神分裂症多基因风险、CM 和精神病样体验(PLE)之间的关系。使用最新的 GWAS 计算了精神分裂症多基因风险评分(SZ-PRS)。首先使用多元线性回归研究了 CM、PRS 和 PLE 之间的关系。接下来,通过结构方程建模,在调整大麻使用、吸烟和神经质等一系列潜在中介因素的情况下,检查了 CM 在 SZ-PRS 和 PLE 之间的路径中介作用。与先前的研究一致,PLE 与 SZ-PRS(B=0.190,p=0.009)和 CM(B=0.575,p<0.001)呈强相关。新颖的是,CM 也与 SZ-PRS 显著相关(B=0.171,p=0.001),并且在 SZ-PRS 对 PLE 的影响中具有重要的中介作用(中介比例=29.9%,p=0.001)。在复制队列中,分析结果相似,同样证实了 CM 的中介作用很强(中介比例=34.7%,p=0.009)。我们的结果表明,CM 是 SZ-PRS 和精神病风险之间因果关系的中介。这些发现为遗传和环境风险之间的关系开辟了新的视角,并需要进一步研究潜在的干预措施,以降低易患精神病的人群的精神病风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/9160238/52102b165802/41398_2022_1975_Fig1_HTML.jpg

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