People with autism spectrum disorder (ASD) had a higher risk of developing Parkinson’s disease early in life, a nationwide population-based study in Sweden showed.

After controlling for birth year, age, and sex, the risk of Parkinson’s disease was four times higher in people with versus without autism (relative risk [RR] 4.43, 95% CI 2.92-6.72), reported Weiyao Yin, MD, PhD, of the Karolinska Institute in Stockholm, and co-authors, in JAMA Neurology.

Risk estimates were similar after adjusting for socioeconomic status, family history of mental illness or Parkinson’s, and age at autism diagnosis, the researchers said. Preterm or early-term birth, an autism risk factor, was not associated with Parkinson’s.

Depression correlated with Parkinson’s risk, independent of autism. Antipsychotic exposure reduced the link between autism and Parkinson’s (RR 2.00, 95% CI 1.27-3.14), but showed no interaction with autism on Parkinson’s risk.

The study was based on all people born in Sweden from 1974 through 1999. Parkinson’s disease in this cohort was very rare: 438 of 2.2 million people without autism (0.02%) had a Parkinson’s diagnosis, compared with 24 of 51,954 people with autism (0.05%).

The findings add to research that suggests a potential biological link between autism and parkinsonism or Parkinson’s disease, including evidence of PARK2 copy number variation in people with autism.

It’s not clear what contributes to the relationship between autism and Parkinson’s, Yin noted.

“One hypothesis is that the brain’s dopamine system is affected in both conditions because dopamine plays a crucial role in social behavior and motor control. Genetic correlation between the two conditions could also contribute to the association,” she wrote in an email to MedPage Today.

“Additionally, antipsychotic exposure partially explained the observed association between ASD and Parkinson’s disease in our study,” Yin continued. “However, even after adjusting for antipsychotic exposure, ASD was still independently associated with a twofold increased risk of Parkinson’s disease. Nevertheless, the possibility of residual confounding by other medications and environmental and behavioral factors associated with Parkinson’s disease remains.”

Yin and colleagues studied all individuals born in Sweden between 1974 and 1999, following them from age 20 until December 2022. Less than half (48.6%) of the cohort was female and the median age at study exit was 34.

Diagnoses were obtained from ICD codes in National Patient Register (NPR) data. Parkinson’s disease was defined as the first-ever diagnosis of Parkinson’s and other idiopathic or degenerative parkinsonian disorders.

“The quality of the NPR has been verified and validated (96%) for ASD,” the researchers wrote. The NPR’s accuracy in detecting parkinsonian disorders is 88%.

Restricting the analysis to idiopathic Parkinson’s disease showed a comparably strong association with autism (RR 3.53, 95% CI 1.86-6.70), Yin and co-authors said. The relationship between autism and Parkinson’s disease remained after adjusting for neuroleptics.

An important limitation of this analysis was that the maximum age at follow-up was under 50, the researchers acknowledged. “The limited follow-up period reduces the ability to observe the progression of Parkinson’s disease, an age-dependent degenerative disease, in individuals with ASD,” they wrote. Future studies with longer follow-up may identify whether autism and late-onset Parkinson’s disease are connected, they added.

“Autism spectrum disorder is a lifelong condition, and more individuals with ASD now progress into middle and older adulthood,” Yin noted.

“This is the first large, longitudinal, population-based study of the future risk of Parkinson’s disease in individuals with ASD,” she continued. “We believe it could stimulate research that sheds light on the unclear causes of Parkinson’s disease and ASD.”