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Mood instability metrics to stratify individuals and measure outcomes in bipolar disorder

Nature Mental Health (2024)Cite this article

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Abstract

Clinical care for bipolar disorder (BD) has a narrow focus on prevention and remission of episodes with pre-/posttreatment reductions in symptom severity as the ‘gold standard’ for outcomes in clinical trials and measurement-based care strategies. Here the study aim was to provide an innovative method for measuring outcomes in BD that has clinical utility and can stratify individuals with BD based on mood instability. The 603 participants comprised those with a BD (n = 385), other or nonaffective disorder (n = 71) or no psychiatric history (n = 147) enrolled in an longitudinal cohort for at least 10 years that collects patient-reported outcome measures (PROMs) assessing depression, (hypo)mania, anxiety and functioning every 2 months. Mood instability was calculated as the intraindividual s.d. of PROMs over 1-year rolling windows and stratified into low, moderate and high thresholds. Individuals with BD had significantly higher 1-year rolling s.d. for depression, (hypo)mania and anxiety compared with psychiatric comparisons (small–moderate effects) and healthy controls (large effects). A significantly greater proportion of scores for those with BD fell into the moderate (depression 50.6%; anxiety 36.5%; and (hypo)mania 52.1%) and high thresholds (depression 9.4%; anxiety 6.1%; and (hypo)mania 10.1%) compared with psychiatric comparisons (moderate 32.3–42.9% and high 2.6–6.6%) and healthy controls (moderate 11.5–31.7% and high 0.4–5.8%). Being in the high or moderate threshold predicted worse mental health functioning (small to large effects). Mood instability, as measured in commonly used PROMs, characterized the course of illness over time, correlated with functional outcomes and significantly differentiated those with BD from healthy controls and psychiatric comparisons. The results suggest a paradigm shift in monitoring outcomes in BD, by measuring intraindividual s.d. as a primary outcome index.

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Fig. 1: Consort diagram.
Fig. 2: Thresholding of 1-year rolling s.d. scores across diagnostic groups.
Fig. 3: Relationship between 1-year rolling s.d. thresholds and mental and physical health functioning.

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Data availability

Data collected at the University of Michigan requires a fully executed Data Use Agreement to be shared outside of the institution. Longitudinal and outcomes data used in the present study, along with data dictionaries, are available subject to review of the proposed analyses and acceptance of a Data Use Agreement. Enquiries can be addressed at http://www.prechterprogram.org/data.

Code availability

Code to calculate the 1-year rolling s.d., MSSD and AR for a mood measure are openly available and provided on an Open Science Framework page: https://osf.io/mj3zk/.

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Acknowledgements

This research was supported by the Heinz C. Prechter Bipolar Research Fund at the University of Michigan (M.G.M.), the Richard Tam Foundation (M.G.M.), the Eisenberg Family Depression Center (M.G.M. and S.H.S.) and is based upon work supported by the Brain and Behavior Research Foundation Young Investigator Award 30719 (S.H.S.), National Institute of Mental Health L30MH127613 (S.H.S.) and National Institute of Mental Health K23MH131601 (S.H.S.). We acknowledge the University of Michigan Prechter Bipolar Longitudinal Research participants and thank the research team of the Prechter Bipolar Research Program for their contributions in the collection and stewardship of the data used in this publication.

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Authors and Affiliations

  1. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

    Sarah H. Sperry, Anastasia K. Yocum & Melvin G. McInnis

  2. Department of Psychology, University of Michigan, Ann Arbor, MI, USA

    Sarah H. Sperry

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Contributions

S.H.S. was involved in conceptualization, funding acquisition, methodology, project administration, validation and writing of the original paper. A.K.Y. was involved in conceptualization, data curation, formal analysis, methodology, visualization and writing of the original paper. M.G.M. was involved in conceptualization, funding acquisition, investigation and writing—review and editing. All data and analyses were independently accessed and verified by S.H.S. and A.K.Y. The Redcap instance for this project is supported by a grant to the Michigan Institute for Clinical and Health Research at the University of Michigan (UM1TR004404).

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Correspondence to Sarah H. Sperry.

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Competing interests

M.G.M. has received consulted and research support from Janssen Pharmaceuticals and has two US patents to the University of Michigan (US Patent nos. 9,685,174 and 11,545,173). A.K.Y. and S.H.S. have no competing interests.

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Nature Mental Health thanks Andrea Fagiolini, Aaron Fisher and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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Appendices 1 and 2, Tables 1–16 and Figs. 1–3.

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Sperry, S.H., Yocum, A.K. & McInnis, M.G. Mood instability metrics to stratify individuals and measure outcomes in bipolar disorder. Nat. Mental Health (2024). https://doi.org/10.1038/s44220-024-00291-5

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