White matter hyperintensities in bipolar disorder: systematic review and meta-analysis
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Updated: Jul 3, 2025

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Published on: May 2, 2025
Tânia Silva1,2,3, Cesar Nunes4, Andreia Ribeiro1,3
1Department of Psychiatry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Background:
White matter hyperintensities are lesions of presumed vascular origin associated with Cerebral small vessel disease. WMH are common findings that and are associated with increased risk of cognitive impairment and dementia. A higher prevalence of WMH has been also reported in patients with bipolar disorder (BD), although the evidence is conflicting.
Objective:
To compare the prevalence of WMH in adults with BD, with the prevalence found in healthy controls.
Methods:
We searched the Embase, Medline/PubMed, and references cited in articles retrieved on May 20, 2023. We included case-control studies that compared the prevalence of WMH in adult BD patients with the prevalence of WMH in healthy controls, using T2-weighted magnetic resonance imaging. We performed a meta-analysis using a random-effects method based on the inverse-variance approach.
Findings:
We included 22 case-control studies reporting data of 1313 people. The overall rate of WMH was 46.5% in BD patients and 28% in controls (pooled Odds Ratio 2.89, 95% CI 1.76; 4.75). We found a moderate heterogeneity across studies (I2 = 0.49). Publication bias was not significant.
Interpretation:
We found evidence that BD patients have a higher burden of WMH than healthy controls. Main limitations were impossibility of analyzing gender differences and bipolar type, moderate heterogeneity between studies, non-representative samples, lack of control for major confounders and search in two electronic databases.
Systematic Review Registration:
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023428464.
Insights
Bipolar disorder patients show a significantly higher prevalence of white matter hyperintensities (WMH) compared to healthy individuals. This meta-analysis highlights a greater WMH burden in those with bipolar disorder.
Area of Science:
- Neuroimaging and Psychiatry
- Cerebral Small Vessel Disease Research
- Cognitive Impairment Studies
Background:
- White matter hyperintensities (WMH) are linked to cerebral small vessel disease and cognitive decline.
- WMH prevalence in bipolar disorder (BD) is debated, necessitating further investigation.
- Understanding WMH in BD is crucial for cognitive impairment and dementia risk assessment.
Approach:
- A systematic literature search was conducted across Embase, Medline/PubMed, and reference lists.
- Meta-analysis of 22 case-control studies involving 1313 participants was performed.
- Prevalence of WMH in adults with BD was compared against healthy controls using T2-weighted MRI.
Key Points:
- The pooled prevalence of WMH was 46.5% in BD patients versus 28% in controls.
- A pooled Odds Ratio of 2.89 (95% CI 1.76; 4.75) indicates a higher likelihood of WMH in BD.
- Moderate heterogeneity (I² = 0.49) was observed across the included studies.
Conclusions:
- Adults with bipolar disorder exhibit a significantly higher burden of white matter hyperintensities.
- Limitations include inability to analyze gender/bipolar type differences and moderate study heterogeneity.
- Further research controlling for confounders and exploring demographic variations is warranted.
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