Moyakhe L B, Dalvie S, Mufford M S, Stein D J, Koen N
Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, South Africa; and UCT Neuroscience Institute.
Biomedical Research and Innovation Platform, SAMRC.
medRxiv. 2023 Mar 31:2023.03.31.23287877. doi: 10.1101/2023.03.31.23287877.
Neurodevelopmental and mental health disorders in childhood constitute an emerging global concern, with adverse sequelae which span children's physical, psychological and social well-being. The aetiology of these disorders is likely complex, multifactorial and polygenic. Polygenic risk scores (PRS), an estimate of an individual's genetic liability toward a disorder, have been increasingly used in psychiatric research to explore genetic associations with disorders of interest. However, limited work delineates polygenic associations with development and mental health in childhood populations.We aimed to systematically review existing literature on associations between genetic risk (as measured by PRS) and neurodevelopmental and mental health outcomes in childhood and adolescence.
Following the recommended Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines, databases were searched using key search terms. The search commenced in March 2021 and concluded in June 2021. The studies eligible for inclusion were full-text articles investigating polygenic risk associations with neurodevelopmental and/or mental health outcomes in childhood or adolescence.
Fourteen studies were eligible for inclusion in this systematic review. The association between higher PRS for attention-deficit/hyperactivity disorder (ADHD) and adverse developmental/mental health outcomes in childhood and adolescence was reported by five studies. Additionally, associations between PRS for bipolar disorder or major depressive disorder and adverse outcomes of interest were also described by two studies; and two studies highlighted associations between schizophrenia PRS and mental health disorders in childhood. The remaining studies highlighted shared polygenic contributions between and within NDDs and mental health disorders in children.
The findings of this systematic review suggest that PRS for neurodevelopmental and mental health disorders may associate with adverse neurodevelopmental and mental health outcomes from early childhood to adolescence. In addition, these associations seemed not to be phenotype-specific, suggesting potential shared genetic variation across the phenotypes of interest.
儿童期神经发育和心理健康障碍已成为全球日益关注的问题，其不良后果涉及儿童的身体、心理和社会福祉。这些障碍的病因可能很复杂，是多因素和多基因的。多基因风险评分（PRS）是对个体患某种疾病的遗传易感性的一种估计，在精神病学研究中越来越多地用于探索与感兴趣的疾病的遗传关联。然而，关于儿童群体中多基因与发育和心理健康之间关联的研究有限。我们旨在系统回顾现有文献，探讨遗传风险（以PRS衡量）与儿童和青少年神经发育及心理健康结果之间的关联。
按照推荐的Meta分析首选报告项目（PRISMA）指南，使用关键搜索词检索数据库。搜索于2021年3月开始，2021年6月结束。符合纳入标准的研究为调查多基因风险与儿童或青少年神经发育和/或心理健康结果之间关联的全文文章。
14项研究符合纳入本系统评价的标准。五项研究报告了注意力缺陷/多动障碍（ADHD）的较高PRS与儿童和青少年不良发育/心理健康结果之间的关联。此外，两项研究还描述了双相情感障碍或重度抑郁症的PRS与感兴趣的不良结果之间的关联；两项研究强调了精神分裂症PRS与儿童心理健康障碍之间的关联。其余研究强调了儿童神经发育障碍（NDDs）和心理健康障碍之间以及内部的多基因共同作用。
本系统评价的结果表明，神经发育和心理健康障碍的PRS可能与从幼儿期到青春期的不良神经发育和心理健康结果相关。此外，这些关联似乎不是表型特异性的，这表明在感兴趣的表型之间可能存在潜在的共享遗传变异。
