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Glutamate System Genes Associated with Ventral Prefrontal and Thalamic Volume in Pediatric Obsessive-Compulsive Disorder

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Abstract

This pilot study was undertaken to determine if there was a significant association between specific glutamate system genes and regional volumes of interest implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Volumetric magnetic resonance imaging (MRI) and genotyping of seven polymorphisms in two genes, glutamate receptor, ionotropic, N-methyl-d-aspartate 2B (GRIN2B) and solute linked carrier, family 1, member 1 (SLC1A1) were conducted in 31 psychotropic-naïve pediatric OCD patients. The rs1805476 variant of GRIN2B was associated with left but not right orbital frontal cortex (OFC) (p = 0.04) and right but not left anterior cingulate cortex (ACC) volume (p = 0.02). The SLC1A1 rs3056 variant was associated with increased total (p = 0.01), left (p = 0.02) and right (p = 0.02) thalamic volume. These results suggest that GRIN2B and SLC1A1 may be associated with regional volumetric alterations in OFC, ACC, and thalamus in children with OCD.

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Acknowledgments

We thank Ms. Tamara Arenovich of the Biostatistics Unit of the Centre for Addiction and Mental Health for statistical support and consultation.

Support was provided by the Ontario Mental Health Foundation through a Type B grant (PDA, MAR, JLK), the Canadian Institutes for Health Research through an operating grant (MOP-38077) (PDA, EM, JLK, MAR) and Fellowship to Dr. Arnold, the National Alliance on Research in Schizophrenia and Depression (Young Investigator Award, PDA), an Obsessive-Compulsive Foundation Research Award (PDA, MAR, JLK), Joe F. Young Sr. Psychiatric Research and Training Program, the Miriam Hamburger Endowed Chair of Child Psychiatry at Children's Hospital of Michigan and Wayne State University and the National Institute of Mental Health (R01MH59299, K24MH02037).

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  1. Program in Genetics and Genomic Biology and Department of Psychiatry, Hospital for Sick Children, Toronto, ON, Canada

    Paul Daniel Arnold

  2. Wayne State University and the Children’s Hospital of Michigan, Detroit, MI, USA

    Frank P. MacMaster, Yousha Mirza, Phillip C. Easter, Michelle Rose & David R. Rosenberg

  3. University of Michigan, Ann Arbor, MI, USA

    Gregory L. Hanna

  4. Anxiety Disorders Clinic, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Margaret A. Richter & Eliza Burroughs

  5. Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Paul Daniel Arnold, Tricia Sicard & James L. Kennedy

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Arnold, P.D., MacMaster, F.P., Hanna, G.L. et al. Glutamate System Genes Associated with Ventral Prefrontal and Thalamic Volume in Pediatric Obsessive-Compulsive Disorder. Brain Imaging and Behavior 3, 64–76 (2009). https://doi.org/10.1007/s11682-008-9050-3

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