Study: Schizophrenia Increases Risk of Late-life Parkinson’s

People with schizophrenia spectrum disorder have an increased risk of developing Parkinson’s disease later in life, according to both regional and nationwide data from Finland.

This higher risk may be associated with medication-induced changes in the brain’s dopamine system — also affected in Parkinson’s patients — or disease-associated mechanisms, and further studies are needed to clarify this, the researchers noted.

Importantly, these findings challenge the prevailing idea that the co-occurrence of Parkinson’s disease and schizophrenia is “rare because these diseases are associated with opposite alterations in the brain’s dopamine system,” Tomi Kuusimäki, the study’s first author and a PhD student at the University of Turku, in Finland, said in a press release.

The study, “Increased Risk of Parkinson’s Disease in Patients With Schizophrenia Spectrum Disorders,” was published in the journal Movement Disorders.

Involved in reward processing and movement, the brain’s dopaminergic system is based on the release of dopamine, a brain messenger molecule, in specific areas of the brain.

Parkinson’s is characterized by a progressive loss of dopamine-producing cells in a brain region that controls movement, while people with schizophrenia typically have an overactive dopamine system, especially in reward-related brain regions.

As such, the main treatments for these conditions typically have opposing mechanisms of action; those mimicking dopamine are used to alleviate Parkinson’s symptoms, whereas those suppressing it are used commonly in schizophrenia patients.

Based on their differences, these conditions are considered to occur rarely in the same person. However, few cases of their co-existence have been reported and some studies have suggested that people with schizophrenia have an increased risk of Parkinson’s, challenging the former idea.

However, none of these studies excluded cases of medication‐induced parkinsonism, which is common in schizophrenia patients treated with antipsychotics that work by suppressing dopamine activity.

Now, researchers in Finland set out to investigate the risk of Parkinson’s disease after a diagnosis of schizophrenia spectrum disorder (SCD) in the Finnish population.  The study, using two different approaches, was funded by the Turku University Hospital, the Instrumentarium Science Foundation, and the Finnish Parkinson Foundation.

In the first approach (regional), the researchers retrospectively analyzed the data from 3,045 Parkinson’s disease patients treated from 2004 to 2019 in southwestern Finland, and 3,045 age- and sex-matched people without the disease (control group).

They assessed the presence of an early diagnosis of SCD and of schizophrenia in Parkinson’s’ patients, case-by-case, considering misdiagnoses and medications. The frequency of SCD and schizophrenia cases in the control group also was assessed.

In the second approach (national), the team used national registers to analyze the frequency of SCD and schizophrenia in 22,189 Parkinson’s patients treated from 1996 to 2015, and in 148,009 age-, sex-, and hospital district-matched individuals without the disease (control group).

All Parkinson’s diagnoses were based on individual clinical examinations by certified neurologists and people with a SCD diagnosis after age 60 or within six years from being diagnosed with Parkinson’s were excluded from both analyses. Some of the Parkinson’s patients in the regional approach also were included in the national data.

Results from both approaches showed that a greater proportion of Parkinson’s patients had been diagnosed previously with SCD than matched controls (0.76% vs. 0.16% in the regional study and 1.5% vs. 1.31% in the national analysis). Similar results were found for a specific schizophrenia diagnosis.

The regional data also showed that people with SCD or schizophrenia were four times more likely to develop Parkinson’s than those without the psychiatric condition, while the national analysis found a 1.17-times higher risk of Parkinson’s among SCD patients only.

The absence of an increased risk for people with schizophrenia in the national approach may be due to the diagnostic classification, as a SCD diagnosis often may precede a schizophrenia diagnosis, the team noted.

“The combined results from more than 20,000 Finnish PD [Parkinson’s disease] patients showed that there is an increased risk for PD among SCD patients,” the researchers wrote, adding that this could be related to the effects of dopamine-suppressing treatments or to a disease-specific “increased vulnerability of the dopamine system.”

“According to our results, a previously diagnosed psychotic disorder or schizophrenia may be one factor that increases the risk of PD later in life,” Kuusimäki said.

The team also emphasized that this increased risk was clearly observed despite the fact that the analyses did not include patients with the most severe SCD, because they usually die before the typical age of Parkinson’s onset.

It is possible that most severe cases of SCD lead “to a particularly increased PD risk over time, a risk that is neutralized by the increased mortality,” the researchers wrote.

Further studies are needed to determine whether and how the severity of psychotic symptoms or the type or dosing of antipsychotic treatments affect the risk of Parkinson’s, the team noted.