Cognitive Impairment in Euthymic Pediatric Bipolar Disorder: A Systematic Review and Meta-Analysis.
OBJECTIVE
To perform a systematic review and meta-analysis of studies investigating neurocognition in euthymic youths with bipolar disorder (BD) compared to healthy controls (HCs).


METHODS
A systematic literature search was conducted in the PubMed/MEDLINE, PsycINFO, and EMBASE databases from inception up until March 23, 2016, for original peer-reviewed articles that investigated neurocognition in euthymic youths with BD compared to HCs. Effect sizes (ES) for individual tests were extracted. In addition, results were grouped according to cognitive domain. This review complied with the PRISMA statement guidelines.


RESULTS
A total of 24 studies met inclusion criteria (N = 1,146; 510 with BD). Overall, euthymic youths with BD were significantly impaired in verbal learning, verbal memory, working memory, visual learning, and visual memory, with moderate to large ESs (Hedge's g 0.76-0.99); significant impairments were not observed for attention/vigilance, reasoning and problem solving, and/or processing speed. Heterogeneity was moderate to large (I2≥ 50%) for most ES estimates. Differences in the definition of euthymia across studies explained the heterogeneity in the ES estimate for verbal learning and memory. We also found evidence for other potential sources of heterogeneity in several ES estimates including co-occurring attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders, and the use of medications. In addition, the use of different neuropsychological tests appeared to contribute to heterogeneity of some estimates (e.g., attention/vigilance domain).


CONCLUSIONS
Euthymic youths with BD exhibit significant cognitive dysfunction encompassing verbal learning and memory, working memory, and/or visual learning and memory domains. These data indicate that for a subset of individuals with BD, neurodevelopmental factors may contribute to cognitive dysfunction.
Translational Psychiatry Research Group Federal University of Ceará, Fortaleza, CE, Brazil.
Liana R
LR
Elias
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
Kamilla W
KW
Miskowiak
Translational Psychiatry Research Group Federal University of Ceará, Fortaleza, CE, Brazil.
Antônio M O
AM
Vale
Translational Psychiatry Research Group Federal University of Ceará, Fortaleza, CE, Brazil.
Cristiano A
CA
Köhler
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
Hanne L
HL
Kjærstad
Health Service and Population Research Department, Institute of Psychiatry, King's College London, UK, and South London and Maudsley National Health Service Foundation Trust, Denmark Hill, London.
Brendon
B
Stubbs
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
Lars V
LV
Kessing
Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro para la Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
Eduard
E
Vieta
Chulalongkorn University, Bangkok, Thailand, and IMPACT Strategic Research Center, Barwon Health, Deakin University, Geelong, VIC, Australia.
Michael
M
Maes
Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Canada.
Benjamin I
BI
Goldstein
Translational Psychiatry Research Group Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: andrefc7@terra.com.br.
André F
AF
Carvalho
D000293:Adolescent; D001714:Bipolar Disorder / Q000453:epidemiology / Q000503:physiopathology*; D002648:Child; D060825:Cognitive Dysfunction / Q000453:epidemiology / Q000503:physiopathology*; D015897:Comorbidity; D006801:Humans
bipolar disorder; cognition; memory; meta-analysis; psychiatry