Autism Linked to Fourfold Increase in Parkinson’s Disease

Autism spectrum disorder (ASD) is linked to a fourfold increased risk for early-onset Parkinson’s disease (PD), results from the largest, population-based cohort study of its kind to date showed.

The findings indicated “that there can be shared biological drivers behind ASD and Parkinson’s disease,” study investigator, Weiyao Yin, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden, said in a release.

“One hypothesis is that the brain’s dopamine system is affected in both cases, since the neurotransmitter dopamine plays an important part in social behavior and motion control,” Yin added.

The study was published online on May 27 in JAMA Neurology.

A Plausible Link

Recent research pointed to a plausible biological link between ASD and PD. However, large, longitudinal studies investigating the risk for PD following an ASD diagnosis are scarce, the researchers noted.

“Our study is the first population-based study, to our knowledge, using prospectively collected data, longitudinal design, and life-course approach to strengthen the inference,” they wrote.

To investigate they used national registry data from more than 2 million individuals born in Sweden between 1974 and 1999 and followed them from age 20 years up to the end of 2022. The median age at study exit was 34 years.

Within this cohort, they identified 51,954 individuals with ASD and 2,226,611 individuals without the disorder.

PD, defined as a first-ever diagnosis of PD or other idiopathic or degenerative parkinsonian disorders, was identified in 438 individuals without ASD (0.02%; 1.3 cases per 100,000 person-years) and in 24 individuals with ASD (0.05%; 3.9 cases per 100,000 person-years), corresponding to a relative risk (RR) of 4.43.

Depression and antidepressant use were present in 46.7% of individuals with ASD, and antipsychotic use, which can cause Parkinson-like symptoms, was present in 31.5%.

Adjusting for depression and antipsychotic use reduced but did not eliminate the association between ASD and PD risk (RR, 3.10 and RR, 2.00, respectively).

Independent of ASD diagnosis, a history of depression and exposure to antipsychotics were linked to a significantly higher risk for PD (RR, 2.01 and RR, 6.34, respectively).

Preterm or early-term birth is a known risk factor for ASD, prompting an examination of its potential association with PD. However, no increased risk for PD was found compared with individuals born at full term.

After adjusting for sex, socioeconomic status, and parental mental illness or PD, the investigators found ASD remained consistently associated with an increased risk for PD.

There are potential biological explanations for the link, Yin told Medscape Medical News.

“One hypothesis suggests that the brain’s dopamine system is impacted in both conditions, as the neurotransmitter dopamine plays a crucial role in social behavior and motor control,” Yin said.

There may be a genetic correlation between the two conditions, she added noting that the PARK2 gene may be associated between ASD and early-onset PD.

“ASD is a lifelong condition, and more children with autism now progress into middle and older adulthood. Healthcare services need to provide long-term monitoring for individuals with ASD — a vulnerable group with high comorbidity and a high use of psychotropic medications,” Yin said.

Experts Weigh In

The study is clinically relevant “mainly because it shows that neurodevelopmental conditions, like ASD, may be associated with clinical signs and diagnoses that may manifest at different ages, and we as clinicians should be aware of that,” Christos Ganos, MD, a neurologist at the Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada, who was not involved with the study, told Medscape Medical News.

“Although neurodevelopmental disorders are diagnosed early in life, there is a need to assess for neurological symptoms and signs also later in life, including to monitor the effects of prescribed medications on neuromotor control,” added Ganos, who is the wolf chair in neurodevelopmental psychiatry, and associate professor of neurology at the University of Toronto, Toronto, Ontario, Canada.

However, he urged caution in linking the specific diagnoses of ASD and PD, as there is a more general link between neurodevelopmental disorders and motor dysfunction.

“Neurodevelopmental disorders are very heterogeneous, and the ‘ASD’ diagnosis encompasses a lot of different disorders and etiologies. Some of these diagnoses/conditions are linked to motor syndromes that are specifically associated with motor slowing but are not PD, although they could resemble some of its features,” he explained.

Strengths of the study include its large sample size and statistical power to provide estimates “with more meaningful precision than prior studies,” said Connie Marras, MD, PhD, a movement disorders specialist, and professor of neurology at the University of Toronto.

However, she noted that investigators did not include smoking in the models, which “may result in an overestimation of the association between ASD and PD,” she added. “Smoking is less common among individuals with ASD and may constitute a confounder. Smoking is also less common in individuals with Parkinson’s disease and is considered a protective factor against PD.”

She also questioned whether the results really have clinical implications for monitoring the emergence of parkinsonism in this population.

“Early detection does not have treatment implications currently, particularly since at present we don’t have therapies for PD prevention or slowing of progression. Once we do have such treatments, then monitoring would be justified,” she said.

However, the finding “could have significant clinical and policy-related implications as these individuals age,” Gregory Wallace, PhD, an autism expert and associate professor of speech, language, and hearing sciences at The George Washington University, Washington, DC, who was not part of the study, told Medscape Medical News.

“Given increased rates of autism diagnoses in younger cohorts, if autistic people are at increased risk for developing parkinsonism as they age, the healthcare system and clinicians who provide care for autistic adults need to be prepared,” said Wallace.

Wallace recently published research showing that co-occurring parkinsonism in adults with autism is linked with lower subjective quality of life, more memory problems, lower sleep quality, and greater depression symptoms.

This study was supported by grants from the Simons Foundation, Swedish Research Council, Karolinska Institutet Research Foundation, and the Beatrice and Samuel A. Seaver Foundation. Yin reported no disclosures. Coauthors’ disclosures included receiving grants from Janssen, MSD, and Takeda outside the submitted work (Ludvigsson), and personal fees for consulting from Abbott Laboratories and Medtronic outside the submitted work (Figee). Ganos, Marras, and Wallace reported no disclosures.