title: COMT and ANKK1 Genetics Interact With Depression to Influence Behavior Following Severe TBI: An Initial Assessment.
abstract: Genetic variations in the dopamine (DA) system are associated with cortical-striatal behavior in multiple populations. This study assessed associations of functional polymorphisms in the ankyrin repeat and kinase domain (ANKK1; Taq1a) and catechol-O-methyltransferase (COMT; Val158Met) genes with behavioral dysfunction following traumatic brain injury (TBI).
  
  
  
  This was a prospective study of 90 survivors of severe TBI recruited from a level 1 trauma center.
  
  
  
  The Frontal Systems Behavior Scale, a self- or family report questionnaire evaluating behavior associated with frontal lobe dysfunction, was completed 6 and 12 months postinjury. Depression was measured concurrently with the Patient Health Questionnaire-9. Study participants were genotyped for Val158Met and Taq1a polymorphisms.
  
  
  
  No statistically significant behavioral differences were observed by Taq1a or Val158Met genotype alone. At 12 months, among those with depression, Met homozygotes (Val158Met) self-reported worse behavior than Val carriers (P = .015), and A2 homozygotes (Taq1a) self-reported worse behavior than A1 carriers (P = .028) in bivariable analysis. Multivariable models suggest an interaction between depression and genetic variation with behavior at 12 months post-TBI, and descriptive analysis suggests that carriage of both risk alleles may contribute to worse behavioral performance than carriage of either risk allele alone.
  
  
  
  In the context of depression, Val158Met and Taq1a polymorphisms are individually associated with behavioral dysfunction 12 months following severe TBI, with preliminary evidence suggesting cumulative, or perhaps epistatic, effects of COMT and ANKK1 on behavioral dysfunction.
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA.
authors.forename: John M
authors.initials: JM
authors.lastname: Myrga
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA.
authors.forename: Shannon B
authors.initials: SB
authors.lastname: Juengst
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, TN.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Failla
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA.
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Arenth
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Grace
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, PA Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA Department of Neuroscience, University of Pittsburgh, Pittsburgh PA Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA wagnerak@upmc.edu.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003863:Depression / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: ANKK1; COMT; DRD2; TBI; behavior; frontal lobe; rehabilomics