Blood-brain barrier imaging as a potential biomarker for bipolar disorder progression

Lyna Kamintsky, Kathleen A. Cairns, Ronel Veksler, Chris Bowen, Steven D. Beyea, Alon Friedman, Cynthia Calkin

Résultat de recherche: Articleexamen par les pairs

85 Citations (Scopus)

Résumé

Bipolar disorder affects approximately 2% of the population and is typically characterized by recurrent episodes of mania and depression. While some patients achieve remission using mood-stabilizing treatments, a significant proportion of patients show progressive changes in symptomatology over time. Bipolar progression is diverse in nature and may include a treatment-resistant increase in the frequency and severity of episodes, worse psychiatric and functional outcomes, and a greater risk of suicide. The mechanisms underlying bipolar disorder progression remain poorly understood and there are currently no biomarkers for identifying patients at risk. The objective of this study was to explore the potential of blood-brain barrier (BBB) imaging as such a biomarker, by acquiring the first imaging data of BBB leakage in bipolar patients, and evaluating the potential association between BBB dysfunction and bipolar symptoms. To this end, a cohort of 36 bipolar patients was recruited through the Mood Disorders Clinic (Nova Scotia Health Authority, Canada). All patients, along with 14 control subjects (matched for sex, age and metabolic status), underwent contrast-enhanced dynamic MRI scanning for quantitative assessment of BBB leakage as well as clinical and psychiatric evaluations. Outlier analysis has identified a group of 10 subjects with significantly higher percentages of brain volume with BBB leakage (labeled the “extensive BBB leakage” group). This group consisted exclusively of bipolar patients, while the “normal BBB leakage” group included the entire control cohort and the remaining 26 bipolar subjects. Among the bipolar cohort, patients with extensive BBB leakage were found to have more severe depression and anxiety, and a more chronic course of illness. Furthermore, all bipolar patients within this group were also found to have co-morbid insulin resistance, suggesting that insulin resistance may increase the risk of BBB dysfunction in bipolar patients. Our findings demonstrate a clear link between BBB leakage and greater psychiatric morbidity in bipolar patients and highlight the potential of BBB imaging as a mechanism-based biomarker for bipolar disorder progression.

Langue d'origineEnglish
Numéro d'article102049
JournalNeuroImage: Clinical
Volume26
DOI
Statut de publicationPublished - 2020

Note bibliographique

Funding Information:
This study was supported by the European Union's Seventh Framework Program ( FP7/EPITARGET ), the Nova Scotia Health Research Foundation (NSHRF), Brain Canada (Platform Support Grant), MITACS, and the Brain & Behavior Research Foundation (NARSAD). The funders of the study had no role in study design, patient recruitment, data collection, analysis, interpretation or publication.

Funding Information:
This study was supported by the European Union's Seventh Framework Program(FP7/EPITARGET), the Nova Scotia Health Research Foundation (NSHRF), Brain Canada (Platform Support Grant), MITACS, and the Brain & Behavior Research Foundation (NARSAD). The funders of the study had no role in study design, patient recruitment, data collection, analysis, interpretation or publication.

Publisher Copyright:
© 2019 The Authors

ASJC Scopus Subject Areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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