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Patients With Bipolar Disorder More Than 3 Times as Likely to Develop PD


A meta-analysis suggests that patients with bipolar disorder have a much greater risk of developing Parkinson disease (PD).

A meta-analysis published this week in JAMA Neurology suggests that patients with bipolar disorder have a much greater risk of developing Parkinson disease (PD).

Both diseases stem from altered dopamine levels in the brain, and the authors suggest that patients who have bipolar disorder and begin to demonstrate features of PD should be screened, after ruling out that the parkinsonism affects are not the result of antipsychotic medication. PD, which includes both motor and nonmotor symptoms, may be preceded by mood disorders by more than 10 years.

The meta-analysis and systematic review included 7 studies and more than 4 million participants. An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019. Data were pooled using a random-effects model, results were abstracted as odds ratios (ORs) and 95% CIs, and heterogeneity was reported as I2.

Overall, the study included 4,374,211 participants; results showed that a diagnosis of bipolar disorder made it 3 times more likely to have a later diagnosis of PD (OR, 3.35; 95% CI, 2.00-5.60; I2 = 92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in patients with bipolar disorder (OR, 3.21; 95% CI, 1.89-5.45; I2 = 94%). Subgroup analyses suggested a possible overestimation in the magnitude of the associations, highlighting the probability that BD may be associated with a later PD diagnosis and the importance of the differential diagnosis of parkinsonism features in individuals with BD.

“When placed in the context of other systematic reviews looking at risk factors for PD, our statistical evidence is highly suggestive,” the authors wrote.

The link between the 2 conditions might be explained by cycles of dopamine levels in the brain, or the dopamine dysregulation hypothesis. The researchers noted that that the cyclical quality of manic states in bipolar disorder “leads to a downregulation of dopamine receptor sensitivity (depression phase), which is later compensated by upregulation (manic state).”

As time goes on, the cycle may lead to an overall reduction of dopaminergic activity, which occurs in PD. The study noted that mood changes are related to the on-time/off-time phenomena in PD. Off-periods in PD are more commonly associated with depressive symptoms, whereas in on-periods, mania-like symptoms are more common.

Further studies are needed, the authors said, as the “processes underlying the on-time/off-time mood states in PD are distinct from sustained abnormal mood fluctuations in BD, including involvement of other neurochemical systems besides dopamine.” In addition, bipolar disorder is not linked with the degeneration of neurons in the brain, they wrote.


Faustino PR, Duarte GS, Chendo I, et al. Risk of developing Parkinson disease in bipolar disorder: a systematic review and meta-analysis [published online October 14, 2019]. JAMA Neurol. doi: 10.1001/jamaneurol.2019.3446.

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