Volume 49, Issue 4 , Pages 378-387, April 2010
Suggestive Linkage of the Child Behavior Checklist Juvenile Bipolar Disorder Phenotype to 1p21, 6p21, and 8q21
Objective
Several studies have documented a profile of elevated scores on the Attention Problems, Aggressive Behavior and Anxious/Depressed scales of the Child Behavior Checklist (CBCL) in youth with bipolar disorder. The sum of these scales, referred to as the CBCL Juvenile Bipolar Disorder (JBD) phenotype, has modest diagnostic utility, and high scores are associated with severity of psychopathology and poor outcome. Recently, a genomewide linkage scan of this measure in ADHD sibling pairs revealed a region of suggestive linkage on chromosome 2q21. The current study aimed to further identify quantitative trait loci that influence the CBCL-JBD phenotype by using a dense and thus, arguably, more powerful set of single-nucleotide polymorphism markers in a different ADHD sibling pair sample.
Method
Subjects were 765 individuals from 154 families with CBCL data enrolled in a linkage study of ADHD. Linkage analyses were completed using a multipoint maximum likelihood variance components approach implemented using the statistical program SOLAR.
Results
Heritability of the CBCL-JBD phenotype was estimated at .71. Although no regions of the genome surpassed empirically derived criteria for significant linkage (p = .000038), peaks on 1p21.1 (p = .00037; LOD = 2.76), 6p21.3 (p = .00054; LOD =2.60), and 8q21.13 (p = .00081; LOD = 2.44) surpassed the threshold for suggestive linkage (p = .002). These regions have been highlighted in genomewide scans of bipolar disorder in adults, schizophrenia, autism, and ADHD.
Conclusions
Findings raise the possibility that genes in these regions influence variation on the CBCL-JBD scale and the emotional and behavioral dysregulation associated with severe psychopathology.
Key Words: juvenile bipolar disorder, CBCL, genomewide linkage
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This article was reviewed under and accepted by Ad Hoc Editor James F. Leckman, M.D..
This work was supported by R01HD37694 to Dr. Faraone and K08MH66072 to Dr. Doyle. Portions of this work were presented at the MGH-Ryan Licht Sang Pediatric Bipolar Disorder Foundation Conference, March 27, 2009, Cambridge, MA.
Disclosure: Dr. Doyle has received research funding from the National Institute of Mental Health, Harvard Medical School, and the Stanley Foundation. She received consulting fees from Pfizer Inc in 2007 and speaker's fees from Reed Education in 2008. Dr. Biederman currently receives research support from the following sources: Alza, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Co., Janssen Pharmaceuticals Inc., McNeil, Merck, Organon, Otsuka, Shire, National Institute of Mental Health (NIMH), and the National Institute of Child Health and Human Development (NICHD). In 2009, Dr. Biederman received a speaker's fee from the following sources: Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, Dr. Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, the National Alliance for Research on Schizophrenia and Depression (NARSAD), National Institute on Drug Abuse (NIDA), New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc., and Wyeth. Dr. Faraone, in the past year, has received consulting fees and has been on Advisory Boards for Eli Lilly and Shire and has received research support from Eli Lilly, Pfizer, Shire, and the National Institutes of Health. In previous years, he has received consulting fees or has been on Advisory Boards or has been a speaker for the following sources: Shire, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. In previous years he has received research support from Eli Lilly, Shire, Pfizer, and the National Institutes of Health. Drs. Ferreira and Smoller, and Ms Wong report no biomedical financial interests or potential conflicts of interest.
This article is discussed in an editorial by Dr. Robert Althoff on page 302.
PII: S0890-8567(10)00084-5
doi:10.1016/j.jaac.2010.01.008
© 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Volume 49, Issue 4 , Pages 378-387, April 2010
