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自闭症谱系障碍个体患帕金森病的风险。

Risk of Parkinson Disease in Individuals With Autism Spectrum Disorder.

作者信息

Yin Weiyao, Reichenberg Abraham, Schnaider Beeri Michal, Levine Stephen Z, Ludvigsson Jonas F, Figee Martijn, Sandin Sven

机构信息

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

出版信息

JAMA Neurol. 2025 May 27. doi: 10.1001/jamaneurol.2025.1284.

Abstract

IMPORTANCE

Recent research suggests a plausible biological link between autism spectrum disorder (ASD) and Parkinson disease (PD). Nonetheless, large longitudinal studies examining the risk of PD following ASD are lacking.

OBJECTIVE

To examine the association between ASD and future PD risk.

DESIGN, SETTING, AND PARTICIPANTS: A nationwide population-based prospective cohort study was performed using data from Swedish national registers. All individuals born in Sweden from 1974 to 1999 with follow-up from age 20 years until December 31, 2022, and with complete covariate data were included. The analysis was completed in August 2024.

EXPOSURES

Diagnoses of ASD as a time-varying exposure obtained from the National Patient Register.

MAIN OUTCOMES AND MEASURES

Diagnoses of PD were obtained from the National Patient Register through 2022. The relative risk (RR) of PD was quantified using incidence rate ratios with 95% CIs from Poisson regression. Preterm birth, depression, antidepressant use, and antipsychotic exposure over time were potentially modifying life events.

RESULTS

The study included 2 278 565 individuals (median [IQR] age at exit, 34 [29-42] years; 1 106 772 female [48.6%]), contributing 33 858 476 person-years. PD occurred in 438 of 2 226 611 individuals without ASD (0.02%; 1.3 cases/100 000 person-years) and 24 of 51 954 individuals with ASD (0.05%; 3.9 cases/100 000 person-years) (RR, 4.43 [95% CI, 2.92-6.72]). The risk estimates were similar after adjusting for sex, socioeconomic status, family history of mental illness, family history of PD, and age at ASD diagnosis. Preterm or early-term birth was not associated with and did not modify the PD risk. Depression and antidepressant use (present in 24 257 individuals with ASD [46.7%]) were associated with increased risk of PD (RR, 2.01 [95% CI, 1.40-2.88]), independent of ASD. Antipsychotic exposure (present in 16 387 individuals with ASD [31.5%]) reduced but did not fully attenuate the association (RR, 2.00 [95% CI, 1.27-3.14]) and showed no interaction with ASD on PD risk.

CONCLUSIONS AND RELEVANCE

ASD was associated with increased risk of PD, even after adjusting for depression or antidepressant use and antipsychotic exposure. These findings suggest a potential shared etiology between neurodevelopmental disorders and PD, and a heightened awareness of long-term neurological conditions in individuals with ASD may be warranted.

摘要

重要性

近期研究表明,自闭症谱系障碍(ASD)与帕金森病(PD)之间可能存在生物学联系。然而,缺乏大型纵向研究来考察ASD后患PD的风险。

目的

探讨ASD与未来患PD风险之间的关联。

设计、设置和参与者:使用瑞典国家登记册的数据进行了一项基于全国人口的前瞻性队列研究。纳入了1974年至1999年在瑞典出生、从20岁开始随访至2022年12月31日且拥有完整协变量数据的所有个体。分析于2024年8月完成。

暴露因素

从国家患者登记册中获取的ASD诊断作为随时间变化的暴露因素。

主要结局和测量指标

通过国家患者登记册获取截至2022年的PD诊断。使用泊松回归的发病率比及95%置信区间对PD的相对风险(RR)进行量化。早产、抑郁、抗抑郁药使用以及随时间推移的抗精神病药物暴露是潜在的影响生活事件。

结果

该研究纳入了2278565名个体(退出时的中位年龄[四分位间距]为34[29 - 42]岁;1106772名女性[48.6%]),贡献了33858476人年。在2226611名无ASD的个体中有438人患PD(0.02%;每100000人年1.3例),在51954名有ASD的个体中有24人患PD(0.05%;每100000人年3.9例)(RR,4.43[95%置信区间,2.92 - 6.72])。在调整了性别、社会经济地位、精神疾病家族史、PD家族史以及ASD诊断时的年龄后,风险估计值相似。早产或足月产与PD风险无关且未改变该风险。抑郁和抗抑郁药使用(在24257名有ASD的个体中存在[46.7%])与PD风险增加相关(RR,2.01[95%置信区间,1.40 - 2.88]),与ASD无关。抗精神病药物暴露(在16387名有ASD的个体中存在[31.5%])降低了但未完全减弱这种关联(RR,2.00[95%置信区间,1.27 - 3.14]),并且在PD风险方面与ASD没有相互作用。

结论及意义

即使在调整了抑郁或抗抑郁药使用以及抗精神病药物暴露后,ASD仍与PD风险增加相关。这些发现提示神经发育障碍与PD之间可能存在共同的病因,对于ASD个体长期神经疾病的认识可能需要提高。

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The epidemiology of Parkinson's disease.帕金森病的流行病学。
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