Importance Associations between childhood infection, IQ, and adult nonaffective psychosis (NAP) are well established. However, examination of sensitive periods for exposure, effect of familial confounding, and whether IQ provides a link between childhood infection and adult NAP may elucidate pathogenesis of psychosis further.

Objectives To test the association of childhood infection with IQ and adult NAP, to find whether shared familial confounding explains the infection-NAP and IQ-NAP associations, and to examine whether IQ mediates and/or moderates the childhood infection-NAP association.

Design, Setting, and Participants Population-based longitudinal cohort study using linkage of Swedish national registers. The risk set included all Swedish men born between 1973 and 1992 and conscripted into the military until the end of 2010 (n = 771 698). We included 647 515 participants in the analysis.

Measurement of Exposures Hospitalization with any infection from birth to age 13 years.

Main Outcomes and Measures Hospitalization with an International Classification of Diseases diagnosis of NAP until the end of 2011. At conscription around age 18 years, IQ was assessed for all participants.

Results At the end of follow-up, the mean (SD) age of participants was 30.73 (5.3) years. Exposure to infections, particularly in early childhood, was associated with lower IQ (adjusted mean difference for infection at birth to age 1 year: –1.61; 95% CI, −1.74 to −1.47) and with increased risk of adult NAP (adjusted hazard ratio for infection at birth to age 1 year: 1.19; 95% CI, 1.06 to 1.33). There was a linear association between lower premorbid IQ and adult NAP, which persisted after excluding prodromal cases (adjusted hazard ratio per 1-point increase in IQ: 0.976; 95% CI, 0.974 to 0.978). The infection-NAP and IQ-NAP associations were similar in the general population and in full-sibling pairs discordant for exposure. The association between infection and NAP was both moderated (multiplicative, β = .006; SE = 0.002; P = .02 and additive, β = .008; SE = 0.002; P = .001) and mediated (β = .028; SE = 0.002; P < .001) by IQ. Childhood infection had a greater association with NAP risk in the lower, compared with higher, IQ range.

Conclusions and Relevance Early childhood is a sensitive period for the effects of infection on IQ and NAP. The associations of adult NAP with early-childhood infection and adolescent IQ are not fully explained by shared familial factors and may be causal. Lower premorbid IQ in individuals with psychosis arises from unique environmental factors, such as early-childhood infection. Early-childhood infections may increase the risk of NAP by affecting neurodevelopment and by exaggerating the association of cognitive vulnerability with psychosis.

儿童感染，智商和成人非情感性精神病（NAP）之间的重要性关联已得到很好的建立。但是，对接触的敏感期，家族混杂的影响以及智商是否在儿童感染和成人NAP之间提供联系的检查可以进一步阐明精神病的发病机理。

目的 测试儿童感染与智商和成人NAP的关系，以发现共有的家庭混杂因素可以解释感染-NAP和IQ-NAP的关联，并检查智商是否介导和/或调节儿童感染-NAP的关联。

设计，设置和参与者 使用瑞典国家注册簿的链接进行基于人口的纵向队列研究。风险范围包括所有在1973年至1992年之间出生并入伍至2010年底的瑞典男子（n = 771 698）。我们在分析中包括647515名参与者。

暴露量的测量 从出生到13岁的任何感染的住院治疗。

主要结果和措施 住院治疗直至2011年底均通过国际疾病分类对NAP进行诊断。在18岁左右的应征者中，对所有参与者的智商进行了评估。

结果 随访结束时，参与者的平均（SD）年龄为30.73（5.3）岁。暴露于感染，尤其是在儿童早期，与智商降低（1岁至出生时感染的调整后平均差异：–1.61； 95％CI，-1.74至-1.47）和成人NAP风险增加（调整后的危险）有关。 1岁以下婴儿的感染率：1.19； 95％CI，1.06至1.33）。较低的病前智商与成人NAP之间存在线性关联，在排除前驱病例后这种趋势仍然存在（智商每增加1点，风险比调整后的比率为0.976； 95％CI为0.974至0.978）。感染-NAP和IQ-NAP的关联在一般人群中和在全兄弟姐妹对中与暴露不符的情况相似。感染和NAP之间的关联均得到了缓解（相乘，β= .006； SE = 0.002；P  = .02和加和物，β= .008；SE = 0.002; P  = .001）， 并由IQ介导（β= .028; SE = 0.002; P <.001）。与较高的智商范围相比，儿童感染与较低的NAP风险具有更大的相关性。

结论和相关性 幼儿期是感染对智商和NAP影响的敏感时期。成人NAP与儿童早期感染和青春期智商之间的关联并不能完全由共同的家庭因素来解释，可能是因果关系。精神病患者的病前智商较低是由独特的环境因素引起的，例如儿童早期感染。儿童早期感染可能会通过影响神经发育和夸大认知脆弱性与精神病的关联而增加NAP的风险。