Large-scale Collaborative Network Valuable for Research in Bipolar Disorder

Over the shoulder view of female psychiatrist writing on clipboard speaking with male patient

Research on bipolar disorder (BD) has always been underfunded compared with other serious psychiatric disorders, especially considering the exceptionally high rates of associated disability and societal costs. What’s more, the available funding is generally split across small, short-term cohort studies that can’t chart a clear path to effective interventions.

To examine the value of large-scale collaboration, researchers at Brigham and Women’s Hospital and colleagues worldwide recently determined core predictors of functional outcome in BD, independent of treatment organization or societal differences.

Reporting in Bipolar Disorders, Katherine E. Burdick, PhD, vice chair for Research in the Department of Psychiatry and director of the Mood and Psychosis Research Program at the Brigham, Caitlin E. Millett, PhD, a postdoctoral research fellow in Psychiatry, and a group of esteemed international colleagues also outline a plan for continued global collaboration.


The initial work included 13 cohorts from 11 universities or consortia (four in the U.S., five in Europe, one in Canada, and one in Australia), who were invited to participate based on existing professional relationships.

Each site was asked how to dichotomize high versus low functioning in their BD cohort(s) based on whichever scale/measure was used in their study. Each was also asked to provide detailed cohort characteristics (demographics, diagnostic, clinical, cognitive, and functional features) to allow the team to design analyses that would align across cohorts.

The Brigham researchers reviewed the listings of variables available at each site and recommended which should be included in further analyses. This decision was based on statistical power considerations and the validity of data collected for each variable. After achieving consensus, sites were asked to conduct logistic regression with functional outcome (high vs. low) as the dependent variable.


This initial exercise aimed to find consistencies across samples and identify where differences exist by individual site. Therefore, the results of each site’s regression were compared descriptively side-by-side, not directly combined.

The analyses included 5,882 individuals with a diagnosis of BD. Consistent with prior research, the prevalence of “lower” functioning across sites was high (ranging from 41% to 75%).

The most commonly reported finding was that depressive symptoms (even subthreshold symptoms) strongly predicted lower community functioning. 10 out of 12 sites (83%) reported depressive symptoms as a contributor.

Several other factors associated with greater impairment were significant (p<0.05) or trend-level significant (p≤0.10) in at least 25% of the sites reporting on that measure:

  • Lower levels of education
  • Greater number of prior manic episodes
  • Greater number of prior depressive episodes
  • Comorbid substance use
  • Comorbid anxiety disorders
  • Greater total number of psychotropic medications used

Global Longitudinal Study Planned

One of the key messages that this paper delivered was that there is an urgent need for a well-resourced prospective, global longitudinal study of BD. The capacity-building exercise described here clarified the following needs:

  • Large samples that reach beyond single sites and encompass the substantial heterogeneity of BD, taking geographic, cultural, and societal considerations into account and including participants from non-European ancestries
  • Comprehensive phenotyping with uniform measures that allow for data sharing and harmonization across studies
  • Long-term, repeated assessment of clinical, cognitive, and functional measures alongside key biomarkers (e.g., genetic, immune, imaging, digital)
  • A centralized coordinating center

It’s hoped that continued collaboration will disentangle core BD features from secondary phenomena, which is impossible in small, one-site studies. BD is one of the most impairing mental health conditions worldwide, and a quicker pace of developing new therapies would make substantive improvements in millions of lives.

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