Cognitive flexibility and performance in children and adolescents with threshold and sub-threshold bipolar disorder
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Greater understanding of cognitive function in children and adolescents with bipolar disorder (BD) is of critical importance to improve our ability to design targeted treatments to help with real-world impairment, including academic performance. We sought to evaluate cognitive performance among children with either BD type I, II, or “not otherwise specified” (NOS) participating in multi-site Course and Outcome of Bipolar Youth study compared to typically developing controls (TDC) without psychopathology. In particular, we sought to test the hypothesis that BD-I and BD-II youths with full threshold episodes of mania or hypomania would have cognitive deficits, including in reversal learning, vs. those BD-NOS participants with sub-threshold episodes and TDCs. N = 175 participants (BD-I = 81, BD-II = 11, BD-NOS = 28, TDC = 55) completed Cambridge Neuropsychological Automated Testing Battery (CANTAB) tasks. A priori analyses of the simple reversal stage of the CANTAB intra-/extra-dimensional shift task showed that aggregated BD-I/II participants required significantly more trials to complete the task than either BD-NOS participants with sub-syndromal manic/hypomanic symptoms or than TDCs. BD participants across sub-types had impairments in sustained attention and information processing for emotionally valenced words. Our results align with prior findings showing that BD-I/II youths with distinct episodes have specific alterations in reversal learning. More broadly, our study suggests that further work is necessary to see the interaction between neurocognitive performance and longitudinal illness course. Additional work is required to identify the neural underpinnings of these differences as targets for potential novel treatments, such as cognitive remediation.
KeywordsBipolar disorder Child Adolescent Cognitive performance Reversal learning
We gratefully thank all participants and their families for being part of this study and the National Institutes of Mental Health (NIMH) for supporting this work—including the Course and Outcome of Bipolar Youth (COBY; R01MH059929), Longitudinal Assessment of Manic Symptoms (LAMS; (R01MH073953, R01MH073801, R01MH073967, R01MH073816), and Dr. Dickstein’s Pediatric Mood, Imaging, and NeuroDevelopment (PediMIND) Program studies (K22MH074945).
Compliance with ethical standards
Conflict of interest
Drs. Dickstein, Axelson, Diler, T. Goldstein, Ryan, Liao, Yen, Horwitz, and Kowatch, as well as Ms. Mary Kay Gill, Ms. Heather Hower, and Ms. Alexandra Weissman report no biomedical financial interests or potential conflicts of interest. Dr. Birmaher has received royalties from Random House, Inc., and Lippincott Williams & Wilkins. Dr. Frazier has received federal funding or research support from, acted as a consultant to, received travel support from, and/or received a speaker’s honorarium from the Simons Foundation, Ingalls Foundation, Forest Laboratories, Ecoeos, IntegraGen, Kugona LLC, Shire Development, Bristol-Myers Squibb, National Institutes of Health, and the Brain and Behavior Research Foundation. Dr. Fristad has received royalties from Guilford Press, American Psychiatric Press, and CFPSI Press. Dr. B. Goldstein is a consultant for BMS, has received research support from Pfizer, and has received speaker’s honoraria from Purdue Pharma. Dr. Hunt is a senior editor of Brown Child and Adolescent psychopharmacology update, and receives honoraria from Wiley Publishers. Dr. Keller receives research support from Pfizer, and has received honoraria from Medtronic. Dr. Strober receives support from the Resnick Endowed Chair in Eating Disorders. Dr. Youngstrom has consulted with Lundbeck and Otsuka. Dr. Arnold has received research funding from Curemark, Forest, Lilly, Neuropharm, Novartis, Noven, and Shire (as well as NIH and Autism Speaks) and has consulted with or been on advisory boards for Gowlings, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Roche, Seaside Therapeutics, Sigma Tau, Shire, and Tris Pharma and received travel support from Noven. Dr. Findling receives or has received research support, acted as a consultant and/or served on a speaker’s bureau for Alexza Pharmaceuticals, American Academy of Child & Adolescent Psychiatry, American Physician Institute, American Psychiatric Press, AstraZeneca, Bracket, Bristol-Myers Squibb, Clinsys, Cognition Group, Coronado Biosciences, Dana Foundation, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson & Johnson, KemPharm, Lilly, Lundbeck, Merck, NIH, Novartis, Noven, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Rhodes Pharmaceuticals, Roche, Sage, Seaside Pharmaceuticals, Shire, Stanley Medical Research Institute, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD.
This study was reviewed and approved by the institutional review boards of all sites prior to the enrollment of any participant. This includes the IRBs of: (1) the Course and Outcome of Bipolar Youth (COBY) study (sites: University of Pittsburgh Medical Center, Brown University, and the University of California Los Angeles); (2) the Longitudinal Assessment of Manic Symptoms (LAMS; sites: University of Pittsburgh, Case-Western Reserve University, University of Cincinnati), and (3) Dr. Dickstein’s Pediatric Mood, Imaging, and NeuroDevelopment (PediMIND) studies. All participants gave their informed consent prior to inclusion in the study.
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