Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Addiction. 2020 Feb;115(2):326-336. doi: 10.1111/add.14813. Epub 2019 Oct 23.
To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors.
A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins).
A total of 3 004 401 people born in Sweden between 1951 and 1998.
The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses.
In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors.
There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.
评估父母物质使用障碍（SUD）是否与后代认知能力较低有关，以及这种关联是否独立于共同的遗传因素。
利用国家瑞典登记处进行基于人群的队列研究。在全人群中进行了线性回归，并增加了协变量的调整。此外，利用同胞子女分析，通过具有越来越高遗传相关性的三种类型的同胞父母（半同胞、全同胞和同卵双胞胎）的固定效应回归，研究了关联的机制。
1951 年至 1998 年期间在瑞典出生的总共 3004401 人。
暴露变量为父母 SUD，表现为国家患者登记处或犯罪登记处有父母一生 SUD 诊断或与物质相关的犯罪定罪。结果是兵役时的认知测试分数和完成义务教育时的最终学校成绩。分析中包括的协变量包括性别、出生年份、父母教育程度、父母移民状况和父母精神共病诊断。
在全人群中，与没有父母 SUD 的人相比，父母 SUD 与兵役时认知测试斯坦因分数降低（4.56，95%置信区间 [CI] 4.55-4.57）和学校成绩 Z 标准化分数降低（-0.43，95% CI 4.43-4.42）有关（认知测试：5.17，95% CI 5.17-5.18；成绩：0.09，95% CI 0.08-0.09）。有证据表明存在剂量反应关系，即父母双方都有 SUD（认知测试：4.17，95% CI 4.15-4.20；成绩：-0.83，95% CI -0.84 至-0.82）与父母一方有 SUD（认知测试：4.60，95% CI 4.59-4.60；成绩：-0.38，95% CI 0.39 至-0.380）相比，认知能力甚至更低。在考虑遗传相关性的同胞子女分析中，这些负相关减弱，表明存在共同的潜在遗传因素。
父母物质使用障碍（SUD）和后代认知功能之间似乎存在共同的遗传因素，这表明认知缺陷可能是 SUD 遗传传递的风险因素。
