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Jump to Key Points The risk for bipolar disorder (BD) is more than three times higher in individuals with Parkinson’s disease (PD) than in those without the condition, a new study showed.
The risk for BD was highest within the first 3 years after PD diagnosis, persisted through later follow-ups, and was largely consistent across ages and sexes.
While early evidence has suggested that BD is a risk factor for a subsequent PD diagnosis, this new study is among the first to suggest the opposite may also be true.
“These findings highlight the need for proactive screening for bipolar disorder in patients with PD, particularly during the early postdiagnosis period,” investigator Yong Ju Baik, MD of the Korean Armed Forces Capital Hospital in Seongnam, South Korea, and colleagues wrote. “In addition, long-term psychiatric monitoring may be warranted given the sustained and evolving risk over time.”
- PD associated with ↑ subsequent BD risk; IRR 3.74.
- BD incidence 13.01/1000 PY in PD vs 3.48 controls.
- Risk highest within 3 years after PD diagnosis; persists long-term.
- Association seen across ages/sexes; relative risk higher <60 years.
- Proactive BD screening + longitudinal psychiatric monitoring warranted in PD.
The study was recently published online in the Journal of Psychiatric Research.
Psychiatric Disorders Common in PD
Psychiatric disorders such as depression and anxiety are common comorbidities among patients with PD, with previous research suggesting patients with PD have nearly double the risk for depression than those without the movement disorder.
Incidence of BD in this population has been less widely studied, investigators noted.
“This relationship is biologically plausible, given shared alterations in dopaminergic, serotonergic, and noradrenergic systems, as well as neuroinflammatory processes and cortico-limbic dysfunction,” they wrote.
To study the connection further, researchers used data from the Korean National Health Insurance Service database from 2012 to 2023, including 5158 patients with PD (53.3% women; 70% aged 60 years or older) and 25,790 matched control individuals in their analysis.
Investigators used a 3-year washout period to ensure a PD diagnosis before the onset of BD and matched patients with control individuals in a 1:5 ratio using propensity scoring. There were no meaningful differences in demographic and clinical features between groups.
The primary outcome was incident BD, which was defined by at least two outpatient diagnoses by psychiatrists.
Elevated Risk Across Age Groups
Among those with PD, 236 were later diagnosed with BD.
PD was associated with a nearly fourfold greater rate of subsequent BD diagnosis (incidence rate ratio [IRR], 3.74; 95% CI, 3.18-4.41), with a rate of BD diagnosis of 13.01 per 1000 person-years in patients with PD, compared with 3.48 per 1000 person-years in the control group.
Among patients with PD aged 60 years or older, the rate of BD diagnosis was even higher (IR, 14.55 per 1000 person-years), corresponding to a more than threefold higher IR than among control individuals (IRR, 3.48; 95% CI, 2.90-4.17).
For those younger than 60 years, the rate of BD diagnosis was lower (IR, 9.27 per 1000 person-years), even though the relative rate of BD was higher (IRR, 5.77; 95% CI, 3.85-8.66).
The incidence of BD was more than four times higher among men with PD and more than three times higher among women with PD than among control individuals.
After adjusting for sex, age, smoking, total cholesterol, BMI, and income, the risk for BD was highest within the first 3 years following a PD diagnosis (adjusted hazard ratio [aHR], 3.55; 95% CI, 2.75-4.59).
Among patients aged 60 years or older, the risk for BD was highest in the first 3 years after PD diagnosis (aHR, 3.56; 95% CI, 2.70-4.69) and declined significantly over 6-9 years (aHR, 1.62; 95% CI, 0.79-3.34).
In contrast, in patients younger than 60 years, estimated BD risk was higher 6-9 years after PD diagnosis (aHR, 13.44; 95% CI, 3.43-52.71) than in the first 3 years (aHR, 3.69; 95% CI, 1.89-7.19). However, investigators noted the wide CIs and said the differences across time periods were not significant and should not be interpreted as a risk for late rebound.
“Given the increased and persistently elevated risk of BD following PD, clinicians should consider proactive psychiatric screening during the early period after PD diagnosis, with continued longitudinal monitoring thereafter,” the authors wrote.
Limitations of the study were potential misclassification and surveillance bias, as well as not evaluating the effects of treatment or interventions on BD risk.
Blurring of Diagnostic Lines?
The authors suggested that various mechanisms might explain the elevated risk for BD, including chronic neuroinflammation and dopaminergic dysfunction.
BD is likely underdiagnosed in a population with PD, possibly due to the blurring of diagnostic lines, Gregory Pontone, MD, MHS, who was not involved in the study, told Medscape Medical News.
He theorized that impulse control disorders, which affect up to 20% of patients with PD, may be a bipolar diathesis.
“If we figure out whether impulse control and bipolar are associated phenomena, that could help inform the treatment of bipolar illness, which is a major problem worldwide,” said Pontone, a geriatric psychiatrist and chief of the Aging, Behavioral and Cognitive Neurology Division at the University of Florida, Gainesville.
“Studies like this are really important because even if these are separate phenomena, we’re going to learn something about mechanisms that will hopefully improve treatment outcomes in the future,” he said.
This study was supported by the Sungshin Women’s University Research Grant. Disclosures for study authors are included in the original article. Pontone disclosed consulting for Cognition Therapeutics and AbbVie.
