Effect of candidate gene polymorphisms on the course of attention deficit hyperactivity disorder

Biederman, Joseph; Petty, Carter R.; Ten Haagen, Kristina S.; Small, Jacqueline; Doyle, Alysa E.; Spencer, Thomas; Mick, Eric; Monuteaux, Michael C.; Smoller, Jordan W.; Faraone, Stephen V.

doi:10.1016/j.psychres.2008.12.016

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Volume 170, Issue 2 , Pages 199-203, 30 December 2009

Effect of candidate gene polymorphisms on the course of attention deficit hyperactivity disorder

Joseph Biederman
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
- Corresponding author. Clinical and Research Program in Pediatric, Psychopharmacology, Yawkey Center, Suite 6A, Massachusetts General Hospital, Boston, MA 02114, USA.
Carter R. Petty
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
Kristina S. Ten Haagen
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
Jacqueline Small
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
Alysa E. Doyle
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
Thomas Spencer
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
Eric Mick
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
Michael C. Monuteaux
- Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, MA, USA
Jordan W. Smoller
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
Stephen V. Faraone
- Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA
- Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA

Received 1 July 2008; received in revised form 25 November 2008; accepted 30 December 2008.

Abstract

The main aim of this study was to examine the association between attention-deficit hyperactivity disorder (ADHD)-associated genes and the course of ADHD. Subjects were derived from identically designed case-control family studies of boys and girls with ADHD and a genetic linkage study of families with children with ADHD. Caucasian probands and family members with ADHD and with available genetic data were included in this analysis (N=563). The course of ADHD was compared in subjects with and without putative risk alleles (DRD4 7-repeat allele, DAT1 10-repeat allele, and 5HTTLPR long allele). The persistence of ADHD (full or subthreshold diagnosis in the last month) was plotted using Kaplan-Meier survival functions and tested with Cox proportional hazard models. Survival analyses revealed that by 25 years of age 76% of subjects with a DRD4 7-repeat allele were estimated to have significantly more persistent ADHD compared with 66% of subjects without the risk allele. In contrast, there were no significant associations between the course of ADHD and the DAT1 10-repeat allele (P=0.94) and 5HTTLPR long allele. Our findings suggest that the DRD4 7-repeat allele is associated with a more persistent course of ADHD.