RESEARCH ARTICLE Transcriptome-Wide Gene Expression in a Rat Model of Attention Deficit Hyperactivity Disorder Symptoms: Rats Developmentally Exposed to Polychlorinated Biphenyls Nadezhda A. Sazonova, 1 Tania DasBanerjee, 2 Frank A. Middleton, 2,3 Sriharsha Gowtham, 2,3 Stephanie Schuckers, 4 and Stephen V. Faraone 2,3 * 1 Department of Electrical and Computer Engineering, the University of Alabama, Tuscaloosa, Alabama 2 Department of Neuroscience and Physiology, State University of New York (SUNY) Upstate Medical University, Syracuse, New York 3 Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York 4 Department of Electrical and Computer Engineering, Clarkson University, Potsdam, New York Received 3 May 2011; Accepted 25 July 2011 Polychlorinated biphenyls (PCB) exposure in rodents provides a useful model for the symptoms of Attention deficit hyperac- tivity disorder (ADHD). The goal of this study is to identify genes whose expression levels are altered in response to PCB exposure. The brains from 48 rats separated into two age groups of 24 animals each (4 males and 4 females for each PCB exposure level (control, PCB utero, and PCB lactational)) were harvested at postnatal days 23 and 35, respectively. The RNA was isolated from three brain regions of interest and was analyzed for differ- ences in expression of a set of 27,342 transcripts. Two hundred seventy-nine transcripts showed significant differential expres- sion due to PCB exposure mostly due to the difference between PCB lactational and control groups. The cluster analysis applied to these transcripts revealed that significant changes in gene expression levels in PFC area due to PCB lactational exposure. Our pathway analyses implicated 27 significant canonical path- ways and 38 significant functional pathways. Our transcriptome- wide analysis of the effects of PCB exposure shows that the expression of many genes is dysregulated by lactational PCB exposure, but not gestational exposure and has highlighted biological pathways that might mediate the effects of PCB exposure on ADHD-like behaviors seen in exposed animals. Our work should further motivate studies of fatty acids in ADHD, and further suggests that another potentially druggable pathway, oxidative stress, may play a role in PCB induced ADHD behaviors. Ó 2011 Wiley Periodicals, Inc. Key words: Aroclor 1254; ADHD; polychlorinated biphenyls; PCBs INTRODUCTION Attention deficit hyperactivity disorder (ADHD) is a common disruptive behavior disorder, which affects 8–12% of children and 4% of adults (Faraone et al., 2003). Our review of 20 twin studies indicates that ADHD has an estimated heritability of 0.76, and meta-analyses of linkage and association studies have impli- cated several candidate genes: DRD4, SLC6A3, DRD5, HTR1B, SNAP25, DBH, and SLC6A4 (Faraone and Mick, 2010). Meta- analyses suggest that these genes have small but statistically signifi- cant effects on susceptibility to ADHD and all have been implicated by neurobiological studies implicating monoamine pathways in the etiology of the disorder. However, despite these encouraging find- ings, genome-wide association studies of ADHD have not impli- cated any gene at a genome-wide level of significance (Lasky-Su et al., 2008; Neale et al., 2008). The less than complete heritability of ADHD, and the difficulty confirming susceptibility genes, indicates that the prevalence of Additional Supporting Information may be found in the online version of this article. *Correspondence to: Stephen V. Faraone, Ph.D., Department Psychiatry, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY 13210. E-mail: sfaraone@childpsychresearch.org Published online 14 September 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.b.31230 How to Cite this Article: Sazonova NA, DasBanerjee T, Middleton FA, Gowtham S, Schuckers S, Faraone SV. 2011. Transcriptome-Wide Gene Expression in a Rat Model of Attention Deficit Hyperactivity Disorder Symptoms: Rats Developmentally Exposed to Polychlorinated Biphenyls. Am J Med Genet Part B 156:898–912. Ó 2011 Wiley Periodicals, Inc. 898 Neuropsychiatric Genetics