Examining the Comorbidity Between Attention Deficit Hyperactivity Disorder and Bipolar I Disorder: A Meta-Analysis of Family Genetic Studies
Publication: American Journal of Psychiatry
Abstract
Objective
The existence of comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar I disorder has been documented in clinical and epidemiological studies, in studies of children and adults, and in diagnosed ADHD and bipolar I patient samples. Yet questions remain about the validity of diagnosing bipolar I disorder in ADHD youth. The authors aim to clarify these issues by reviewing family genetic studies of ADHD and bipolar I disorder.
Method
The authors applied random-effects meta-analysis to family genetic studies of ADHD and bipolar I disorder. Twenty bipolar proband studies provided 37 estimates of the prevalence of ADHD in 4,301 relatives of bipolar probands and 1,937 relatives of comparison probands. Seven ADHD proband studies provided 12 estimates of the prevalence of bipolar I disorder in 1,877 relatives of ADHD probands and 1,601 relatives of comparison probands.
Results
These studies found a significantly higher prevalence of ADHD among relatives of bipolar probands and a significantly higher prevalence of bipolar I disorder among relatives of ADHD probands. These results could not be accounted for by publication biases, unusual results from any one observation, sample characteristics, or study design features. The authors found no evidence of heterogeneity in the ADHD or bipolar family studies.
Conclusions
The results suggest that ADHD plus bipolar comorbidity cannot be accounted for by misdiagnoses, but additional research is needed to rule out artifactual sources of comorbidity. More research is also needed to determine whether comorbidity of ADHD and bipolar I disorder constitutes a familial subtype distinct from its constituent disorders, which if confirmed would have implications for diagnostic nosology and genetic studies.
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History
Received: 18 January 2012
Revision received: 19 April 2012
Accepted: 11 June 2012
Published online: 1 December 2012
Published in print: December 2012
Authors
Funding Information
Dr. Faraone has received consulting fees and support from Alcobra and Shire and support from NIH; has received consulting or advisory board fees or participated in continuing medical education programs sponsored by Eli Lilly, Janssen, McNeil, Novartis, Pfizer, and Shire; and has received royalties from Guilford Press and Oxford University Press. Dr. Biederman has received support from Elminda, Janssen, McNeil, and Shire; has received speakers fees from Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association; has received research support, consultation fees, or speakers fees from Abbott, Alza, AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, Merck, NARSAD, National Institute on Drug Abuse, New River, National Institute of Child Health and Human Development, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, the Prechter Foundation, Shire, the Stanley Foundation, UCB Pharma, and Wyeth. Dr. Wozniak has received speaking fees from McNeil, Primedia/Massachusetts General Hospital Psychiatry Academy; has served on advisory boards for Pfizer and Shire; and has received research support from Eli Lilly, McNeil, NIMH, and Shire. Dr. Wozniak’s spouse has served on speakers bureaus for Boehringer-Ingelheim, Cephalon, GlaxoSmithKline, King, Sanofi-Aventis, Sepracor, Takeda; has served on advisory boards for Axon Labs, Boehringer-Ingelheim, GlaxoSmithKline, Jazz Pharmaceuticals, Neurogen, Novartis, Novadel Pharma, Pfizer, Sepracor, Takeda, and UCB (Schwarz) Pharma; and has received research support from Boehringer-Ingelheim, GlaxoSmithKline, Sepracor, and UCB (Schwarz) Pharma.
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