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People with bipolar disorder had significantly greater risk of later developing Parkinson's disease than the general population, data from nearly 4.4 million people showed.

Pooled data in a meta-analysis indicated that previous diagnosis of bipolar disorder increased the likelihood of a subsequent diagnosis of idiopathic Parkinson's disease by more than three times (OR 3.35, 95% CI 2.00-5.60), reported Joaquim Ferreira, MD, PhD, of the University of Lisbon in Portugal, and co-authors, in .

"Although there were already single studies suggesting the association between bipolar disorder and Parkinson's disease, our study pools the best studies available for the first time and establishes a more conclusive relationship between these two diseases," said Ferreira.

"This risk was unknown until now and clearly not assumed in the clinical practice of psychiatrists and neurologists," he told 名媛直播. "Bipolar patients who begin developing symptoms similar to those of Parkinson's disease may actually have both diseases. 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."

This analysis also opens the door to investigate biological links between bipolar disorder and Parkinson's, he added.

Longitudinal studies, including a recent analysis in Taiwan, have shown associations between the two conditions that persisted even after adjusting for mood stabilizers. While a causal relationship remains elusive, bipolar illness and Parkinson's may be connected in several ways, observed Gregory Pontone, MD, MHS, of the Johns Hopkins University School of Medicine in Baltimore, who was not involved with the study.

"One possibility is that bipolar disorder, depression, and even anxiety -- the affective illnesses -- create some sort of neurological scar or damage that either opens a window for subsequent neuropathology, or erodes or dysregulates some of the same neurotransmitter pathways that make 'fertile ground' for neurodegenerative disorders to enter," Pontone told 名媛直播.

Another possibility is that some bipolar cases could be prodromal Parkinson's: "A neurodegenerative disorder like Parkinson's may be in early stages, where it might be affecting the limbic circuit and hasn't yet reached the part of the brain responsible for motor symptoms," he said.

There also may be overlap in genetic risk between the two conditions and increased risk of Parkinson's disease and parkinsonism from lithium and anti-psychotic drugs used in bipolar treatment, the researchers added.

In their , Ferreira and co-authors looked at seven studies spanning 4,374,211 people that reported data about the likelihood of developing Parkinson's disease in people with and without bipolar disorder. Four were cohort studies and three were cross-sectional. Five of the seven studies were considered to have low overall risk of bias. One cross-sectional study that enrolled a population of veterans was excluded from the meta-analysis because of doubts over internal and external validity. Most studies did not state the criteria used to establish a Parkinson's disease diagnosis.

After studies with a high risk of bias were removed from the meta-analysis in a sensitivity analysis, the relation between bipolar disorder and Parkinson's remained strong (OR 3.21; 95% CI 1.89-5.45; I²=94%).

Subgroup analysis showed bipolar patients with more than 9 years of follow-up (OR 1.75, 95% CI 1.36-2.26; I²=0%) and less than 9 years of follow-up (OR 5.20, 95% CI 4.26-6.35; I²=34%) also each had a higher risk of Parkinson's diagnosis than people without bipolar disorder.

The greater likelihood of Parkinson's diagnosis in shorter studies may generate "concern over the misdiagnosis of parkinsonism (probably drug-induced in origin) as Parkinson's disease and residual confounding," the researchers wrote. One study explicitly did not differentiate between parkinsonism and Parkinson's disease, which might have caused associations in the meta-analysis to be overestimated. "However, in the subgroup with longer follow-up, where the likelihood of misclassification is expected to be lower, the association was strong and without statistical heterogeneity," the authors noted.

This should reinforce the importance of differential diagnosis between parkinsonism and Parkinson's disease in people with bipolar disorder, they added. "The main message for clinical practice is the alert that patients with bipolar disorder may later develop Parkinson's, and in those patients Parkinson's disease should be formally diagnosed and properly treated," Ferreira said.

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