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Relationship between cognitive flexibility and subsequent course of mood symptoms and suicidal ideation in young adults with childhood-onset bipolar disorder

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Abstract

Neurocognitive deficits, such as cognitive flexibility impairments, are common in bipolar disorder (BD) and predict poor academic, occupational, and functional outcomes. However, the association between neurocognition and illness trajectory is not well understood, especially across developmental transitions. This study examined cognitive flexibility and subsequent mood symptom and suicidal ideation (SI) course in young adults with childhood-onset BD-I (with distinct mood episodes) vs. BD-not otherwise specified (BD-NOS) vs. typically-developing controls (TDCs). Sample included 93 young adults (ages 18–30) with prospectively verified childhood-onset DSM-IV BD-I (n = 34) or BD-NOS (n = 15) and TDCs (n = 44). Participants completed cross-sectional neuropsychological tasks and clinical measures. Then participants with BD completed longitudinal assessments of mood symptoms and SI at 6-month intervals (M = 39.18 ± 16.57 months of follow-up data). Analyses included ANOVAs, independent-samples t tests, chi-square analyses, and multiple linear regressions. Participants with BD-I had significant deficits in cognitive flexibility and executive functioning vs. BD-NOS and TDCs, and impaired spatial working memory vs. TDCs only. Two significant BD subtype-by-cognitive flexibility interactions revealed that cognitive flexibility deficits were associated with subsequent percentage of time depressed and with SI in BD-I but not BD-NOS, regardless of other neurocognitive factors (full-scale IQ, executive functioning, spatial working memory) and clinical factors (current and prior mood and SI symptoms, age of BD onset, global functioning, psychiatric medications, comorbidity). Thus, cognitive flexibility may be an important etiological brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD-I, as this deficit appears to endure into young adulthood and is associated with worse prognosis for subsequent depression and SI.

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Acknowledgements

We gratefully acknowledge research funding from E. P. Bradley Hospital and the National Institute of Mental Health, which supported this work. We also acknowledge and thank study participants and their families for their time and effort completing these studies, without which this research would not be possible.

Funding

This study was supported by E. P. Bradley Hospital and the National Institute of Mental Health grant R01MH087513 (PI: Dickstein). Young adult participants with bipolar disorder were recruited from Brown University’s site of the Course and Outcome of Bipolar Youth (COBY) study R01MH59691 (PIs: Keller/Yen) and the Predicting Adult Outcomes in Bipolar Youth (PROBY) study R01MH112543 (PI: Yen). The funders had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

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Correspondence to Heather A. MacPherson.

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Conflict of interest

Dr Dickstein receives research support from the NIMH and the Brain and Behavior Research Foundation (NARSAD). Dr. Thomas is partially supported by Institutional Development Award Number U54GM115677 from the National Institute of General Medical Sciences of the NIH, which funds Advance Clinical and Translational Research. Dr. Yen receives research support from the NIMH, NICCH, and AFSP and had served as a consultant at Janssen Global Services. Ms. Hower receives honorarium from the U.S. Department of Defense and research support from the NIMH. Dr. Hunt receives honoraria from Wiley Publishers and Lifespan Physician Group, and research support from the NIMH. Dr. Keller receives research support from the NIMH and donor gifts from The John J. McDonnell and Margaret T. O’Brien Foundation. Drs. MacPherson, Kudinova, Kim, Radoeva, and Babcock Fenerci, and Ms. Schettini, Jenkins, and Gilbert declare that they have no conflict of interest to disclose.

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Written informed consent was obtained from all participants prior to study inclusion. Procedures were approved and overseen by the Institutional Review Boards of Bradley Hospital and Brown University, and therefore, the described research has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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The original online version of this article was revised due to update in funding information.

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MacPherson, H.A., Kudinova, A.Y., Schettini, E. et al. Relationship between cognitive flexibility and subsequent course of mood symptoms and suicidal ideation in young adults with childhood-onset bipolar disorder. Eur Child Adolesc Psychiatry 31, 299–312 (2022). https://doi.org/10.1007/s00787-020-01688-0

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