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Increased Parkinson Risk in Bipolar Disorder

October 15, 2019

By Will Boggs MD

NEW YORK—The risk for Parkinson disease appears to be much higher in people with bipolar disorder than in the general population, according to a systematic review and meta-analysis.

"Although there were already single studies suggesting the association between bipolar disorder and Parkinson disease, our study pools, for the first time, all the best studies available and establishes a more conclusive relationship between these two diseases," Dr. Joaquim J. Ferreira of Faculdade de Medicina da Universidade de Lisboa, in Lisbon, told Reuters Health by email.

Parkinson disease is a dopaminergic disorder, and there is evidence of a role of the dopaminergic system in bipolar disorder. Dr. Ferreira and colleagues evaluated the possible association of bipolar disorder with a later diagnosis of idiopathic Parkinson disease based on four cohort studies and three cross-sectional studies; combined, these included more than 65,000 patients with bipolar disorder.

After exclusion of one cross-sectional study because of doubts over external and internal validity, a previous diagnosis of bipolar disorder was associated with a significant 3.35-fold increase in the odds of subsequent diagnosis of Parkinson disease.

The estimate remained essentially unchanged after further exclusion of studies with a high risk of bias, the researchers report in JAMA Neurology, online October 14.

The increased risk of Parkinson disease was evident among individuals with both more and less than nine years of follow-up, although the subgroup with the shorter follow-up had a significantly greater increase in the odds of Parkinson disease diagnosis (5.20-fold) than did the subgroup with longer follow-up (1.75-fold).

"Patients with bipolar disorder may later develop Parkinson disease, and in those patients Parkinson disease should be formally diagnosed and properly treated," Dr. Ferreira said. "Bipolar patients who begin developing, throughout the course of their disease, symptoms similar to those of Parkinson disease may actually have both diseases, and physicians should suspect that those features of parkinsonism may not be just a side effect of the medication used in the treatment of bipolar disorder."

"In addition to the important implications for clinical practice of psychiatrists and neurologists, it opens the door to investigate the biological link between these two clinical entities and also reopens the discussion on the possible long-term side-effects of antipsychotic drugs," he added.

Dr. Mu-Hong Chen from Taipei Veterans General Hospital, in Taiwan, whose recent nationwide longitudinal study found an increased incidence of Parkinson disease in patients with bipolar disorder, told Reuters Health physicians should "monitor for early signs of Parkinson disease in bipolar patients."

Dr. Gregory Pontone, director of the Parkinson's Neuropsychiatry Clinical Programs at Johns Hopkins University School of Medicine, in Baltimore, Maryland, said, "Currently there are no disease-modifying medications for the prevention of Parkinson disease. However, exercise has been shown to reduce the severity and slow progression of Parkinson."

"For now, however, the association between BPAD (bipolar affective disorder) and PD (Parkinson disease) may help in early detection," Dr. Pontone told Reuters Health by email. "For example, if a species or subtype of BPAD (e.g., late onset) is found to have an even greater risk of PD, perhaps that would trigger DaTscan (a dopamine transporter imaging technique), RBD (REM behavior disorder) testing, or genetic tests for PD, leading to early diagnosis of PD before motor symptoms are present."

"I think it would be interesting to know if duration of bipolar illness (or BPAD 1 versus BPAD 2) modifies the risk of PD or the age of onset of PD," he said. "Assuming that BPAD is a risk factor, would longer or more severe (e.g., mania vs. hypomania) illness increase the risk or cause an earlier onset of PD? Our group found that panic disorder was associated with an almost decade earlier onset of PD."

"Another possibility is that some BPAD is actually the result of prodromal Parkinson's disease and possibly the dysregulation of monoamine circuits," Dr. Pontone said. "Given both diseases have typical ages of onset (BPAD is bimodal, one peak in the twenties and one later in life) it would be interesting to see if age of onset for either condition is skewed outside its normal range when they occur together in the same individual."


JAMA Neurol 2019.

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