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Parkinson's Tied to Bipolar Disorder

— Trends emerge even after adjusting for mood stabilizers

MedpageToday
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People with bipolar disorder had a higher risk of Parkinson's disease than people without the disorder, a longitudinal study in Taiwan showed.

A bipolar diagnosis upped the chance of Parkinson's disease by nearly 7 times, Mu-Hong Chen, MD, PhD, of Taipei Veterans General Hospital in Taiwan, and colleagues reported in .

The trend was significant even in adults younger than age 65, and the frequency of psychiatric admissions for manic/mixed and depressive episodes correlated with Parkinson's risk.

"Previous studies have shown a relationship between depression and Parkinson's disease, but few studies have looked at whether there is a relationship between bipolar disorder and Parkinson's," Chen said in a statement.

What Parkinson's and bipolar disorder share is unclear, but "could include genetic alterations, inflammatory processes, or problems with the transmission of messages between brain cells," he suggested. "If we could identify the underlying cause of this relationship, that could potentially help us develop treatments that could benefit both conditions."

Mood disorders are the most common psychiatric disturbances associated with Parkinson's and may present before or after the onset of motor symptoms, noted Gregory Pontone, MD, MHS, of the Johns Hopkins University School of Medicine in Baltimore, and Giacomo Koch, MD, PhD, of the Santa Lucia Foundation in Rome, in an .

"Although both major depression and bipolar disorder are mood disorders that may be characterized by recurrent episodes of low mood (depression), bipolar disorder also requires the presence of ≥1 manic or mixed episodes," they wrote. "Despite the clinical similarities and possibility of etiologic overlap, major depression and bipolar disorder have differing genetic risk."

In this study, Chen and co-authors looked at 56,340 adults in the Taiwan National Health Insurance Research Database who had been diagnosed with bipolar disorder from 2001 through 2009 and who had no history of Parkinson's disease, comparing them with 225,360 age- and sex-matched controls. They followed both groups until December 31, 2011.

The average age in the study was about 40. The prevalence of cerebrovascular diseases, traumatic brain injury, hypertension, dyslipidemia, and diabetes was similar in each group.

During the study, 0.7% of people with bipolar disorder developed Parkinson's disease, compared with 0.1% of controls (P< 0.001). After adjusting for demographic data and medical history, people with bipolar disorder showed a hazard ratio of 6.78 for developing Parkinson's disease compared with controls (95% CI 5.74-8.02). The association was seen both in people under age 65 (HR 12.02, 95% CI 9.33-15.51) and in those 65 and older (HR 3.87, 95% CI 3.05-4.09).

Overall, people with bipolar disorder were diagnosed with Parkinson's disease at a younger age (64.25 years) than controls (72.99 years, P< 0.001).

The likelihood of Parkinson's rose with the number of annual psychiatric admissions. Overall, bipolar patients who were hospitalized more than twice a year were about 6 times more likely to develop Parkinson's disease than those hospitalized less than once a year.

Trends remained even after a series of sensitivity analyses, including one to minimize the chance that iatrogenic parkinsonism was produced by mood-stabilizing treatments such as antipsychotics.

The findings should be viewed in the context of several limitations, Pontone and Koch noted. In studies like this, it's difficult to know when the pathologic process of Parkinson's begins. "For instance, many believe that the disease is active many years or even decades before the onset of motor symptoms, in which case bipolar disorder or mood dysregulation approximating bipolar disorder may more appropriately be viewed as an early symptom of Parkinson's disease," they wrote.

Genetic factors also could play a role in an association between bipolar disorder and Parkinson's disease, they noted. And despite controlling for antipsychotic drugs, the risk that some Parkinson's disease identified in this study was actually drug-induced parkinsonism remains a possibility, they added.

"Mood and movement are linked at the level of treatment in that antipsychotic and mood-stabilizing treatments often lead to movement disorders, including tardive dyskinesia, tremor, acute dystonia, and parkinsonism," Pontone and Koch observed.

The nature of this connection may be key: "In the case of bipolar disorder as a risk factor for Parkinson's disease, identifying the underlying cause of this relationship might allow the early detection of Parkinson's disease and inform the development of disease-modifying therapies that could benefit both conditions," they wrote.

Disclosures

The study was supported by Taipei Veterans General Hospital and the Taiwanese Ministry of Science and Technology.

The researchers reported no relevant disclosures. The editorialists reported a relationship with Acadia Pharmaceuticals Inc.

Primary Source

Neurology

Huang M-S, et al "Bipolar disorder and risk of Parkinson disease: A nationwide longitudinal study" Neurology 2019; DOI:10.1212/WNL.0000000000007649.

Secondary Source

Neurology

Pontone G, Koch G "An association between bipolar disorder and Parkinson disease: When mood makes you move" Neurology 2019; DOI:10.1212/WNL.0000000000007641.