The catechol-O-methyltransferase (COMT) gene is the predominant means of dopamine deactivation within the prefrontal cortex (PFC), a brain locus implicated in Attention deficit/hyperactivity disorder (ADHD). Dopamine dysregulation is a significant contributor to the pathophysiology of ADHD and Methylphenidate (MPH), an effective treatment for ADHD, and acts at least in part, through modulation of dopamine levels in the PFC. Thus, we tested the hypothesis that the Catechol-O-Methyltransferase (COMT) Val108/158 Met polymorphism modulates behavioral dimensions relevant for ADHD and/or response of these behavioral dimensions to MPH and/or neuropsychological functions considered relevant for ADHD. No genotype or genotype by treatment interaction effects were observed for behavioral response to MPH. No genotype effects were observed using the family-based approach. Marginal genotype effects were observed between the Met/Met genotype and some but not all aspects of executive functioning. Overall, these results do not support the implication of the COMT Val108/158 Met polymorphism in ADHD, ADHD relevant behaviours or response to methylphenidate, but weakly implicate COMT gene in some aspects of executive functions in children with ADHD. Given that gene effects on behaviours are likely to be very small, a much large sample would be needed in order to establish these results, both negative and positive, with better confidence.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.112389 |
| Date | January 2008 |
| Creators | Choudhry, Zia Ulhaq. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Psychiatry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002698819, proquestno: AAIMR51079, Theses scanned by UMI/ProQuest. |
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