Bipolar disorder and Parkinson disease link

Movement disorders

By Mardi Chapman

18 Oct 2019

People with bipolar disorder have more than a three-fold increased risk of developing Parkinson disease later in life.

A systematic review of the literature identified seven cohort and cross-sectional studies, with more than four million participants, comparing the likelihood of developing idiopathic PD in bipolar and non-bipolar populations.

The meta-analysis found that a previous diagnosis of bipolar disorder significantly increased the risk of a subsequent PD diagnosis with an odds ratio of 3.35.

A sensitivity analysis, after removing studies that had a high risk of bias, also showed a consistently increased risk of PD in people with BD (OR 3.21).

According to the authors of the study, published in JAMA Neurology, the “pathophysiological rationale between BD and PD might be explained by the dopamine dysregulation hypothesis”.

“Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical PD state. This hypothesis justifies the highly suggestive association we found of BD with PD,” the researchers said.

Mood changes related to the on-time/off-time phenomena may also reinforce the link between bipolar disorder and PD.

“However, it should be mentioned that BD is not associated with overt evidence of neurodegeneration, and while mood phenomena fluctuations may be similar, 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.”

They said standard treatment for bipolar disorder including lithium, antipsychotic and antiepileptic medications may be associated with drug-induced parkinsonism, which is not clinically distinguishable from Parkinson disease.

“However, treatment with lithium is foundational in BD, and so to separate the causal effect from a potential confounder would be particularly difficult,” the said.

“The main clinical implication of this review should be to underline that if patients with BD present with parkinsonism features, this may not be drug induced and may recommend the investigation of PD.”

“To clinically distinguish parkinsonism from PD in clinical practice, the use of functional neuroimaging methods may be of particular interest, as PD classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”

“Additionally, there are implications for the care of patients with BD, namely with longitudinal motor assessments, monitoring for prodromal motor or nonmotor signs of PD, and eventually by parkinsonism risk mitigation via medication selections and nonpharmacological treatments.”


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