Observational studies have found loneliness and social isolation to mediate the relationship between childhood maltreatment and schizophrenia. Limitations with observational studies (e.g., confounding and reverse causation), however, have meant the robustness of these relationships has thus far not been explored. To address this gap, the current study utilized genomic structural equation modeling (genomic SEM) and Mendelian randomization (MR) to perform a genetic mediation analysis between childhood maltreatment, loneliness/isolation, and schizophrenia, using summary statistics from three genome-wide association studies (sample sizes 105,318-487,647). While we observed a putative effect of both childhood maltreatment (inverse variance weighted OR = 3.44 per standard deviation increase, 95% confidence interval [CI] [1.66-7.13], p < .001) and loneliness/isolation (OR = 2.98, 95% CI [1.37-6.46], p = .006) on schizophrenia, our hypothesis that loneliness/isolation would mediate the relationship between childhood maltreatment and schizophrenia was not supported (genomic SEM indirect effect = -0.05, SE = 0.05, p = .255; MR indirect effect = 0.10, SE = 0.11, p = .369). Furthermore, reverse mediation analysis indicated that the effect may be in the opposite direction (genomic SEM indirect effect = 0.11, SE = 0.02, p < .001; MR indirect effect = 0.01, SE = 0.00, p < .001), accounting for 20.3%-28.9% of the total effect. The current results suggest that intervening in loneliness/isolation in individuals with a history of childhood maltreatment is unlikely to reduce schizophrenia risk. On the contrary, targeting loneliness/isolation in individuals with a genetic predisposition toward schizophrenia may diminish childhood maltreatment risk. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

中文翻译：

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孤独和社会孤立在调节儿童虐待和精神分裂症之间关系中的作用：一种遗传信息方法。


观察性研究发现孤独和社会孤立可以调节儿童虐待与精神分裂症之间的关系。然而，观察性研究的局限性（例如混杂和反向因果关系）意味着迄今为止尚未探索这些关系的稳健性。为了解决这一差距，当前的研究利用基因组结构方程模型（基因组 SEM）和孟德尔随机化（MR），利用三项全基因组关联研究的汇总统计数据，对儿童虐待、孤独/孤立和精神分裂症之间进行遗传中介分析。 （样本量 105,318-487,647）。虽然我们观察到儿童虐待（逆方差加权 OR = 3.44 每标准差增加，95% 置信区间 [CI] [1.66-7.13]，p < .001）和孤独/孤立（OR = 2.98, 95）的推定影响% CI [1.37-6.46]，p = .006）关于精神分裂症，我们关于孤独/隔离会介导儿童虐待与精神分裂症之间关系的假设并未得到支持（基因组 SEM 间接效应 = -0.05，SE = 0.05，p = . 255；MR 间接效应 = 0.10，SE = 0.11，p = .369）。此外，反向中介分析表明，效应可能是相反的方向（基因组 SEM 间接效应 = 0.11，SE = 0.02，p < .001；MR 间接效应 = 0.01，SE = 0.00，p < .001），占占总效果的20.3%-28.9%。目前的结果表明，对有童年虐待史的个体进行孤独/隔离干预不太可能降低精神分裂症的风险。相反，针对具有精神分裂症遗传倾向的个体的孤独/隔离可能会降低儿童虐待风险。 （PsycInfo 数据库记录 (c) 2024 APA，保留所有权利）。