title: Interaction between COMT rs5993883 and second generation antipsychotics is linked to decreases in verbal cognition and cognitive control in bipolar disorder.
abstract: BACKGROUND
  Second generation antipsychotics (SGAs) are increasingly utilized in Bipolar Disorder (BD) but are potentially associated with cognitive side effects. Also linked to cognitive deficits associated with SGA-treatment are catechol-O-methyltransferase (COMT) gene variants. In this study, we examine the relationship between cognition in SGA use and COMT rs5993883 in cohort sample of subjects with BD.
  
  
  METHODS
  Interactions between SGA-treatment and COMT rs5993883 genotype on cognition was tested using a battery of neuropsychological tests performed in cross-sectional study of 246 bipolar subjects.
  
  
  RESULTS
  The mean age of our sample was 40.15 years and was comprised of 70 % female subjects. Significant demographic differences included gender, hospitalizations, benzodiazepine/antidepressant use and BD-type diagnosis. Linear regressions showed that the COMT rs5993883 GG genotype predicted lower verbal learning (p = 0.0006) and memory (p = 0.0026) scores, and lower scores on a cognitive control task (p = 0.004) in SGA-treated subjects. Interestingly, COMT GT- or TT-variants showed no intergroup cognitive differences. Further analysis revealed an interaction between SGA-COMT GG-genotype for verbal learning (p = 0.028), verbal memory (p = 0.026) and cognitive control (p = 0.0005).
  
  
  CONCLUSIONS
  This investigation contributes to previous work demonstrating links between cognition, SGA-treatment and COMT rs5993883 in BD subjects. Our analysis shows significant associations between cognitive domains such as verbal-cognition and cognitive control in SGA-treated subjects carrying the COMT rs5993883 GG-genotype. Prospective studies are needed to evaluate the clinical significance of these findings.
authors.affiliation: Clinical Pharmacy Department, College of Pharmacy, University of Michigan, 428 Church St, Ann Arbor, MI, 48109-106, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Flowers
authors.affiliation: Department of Psychiatry, School of Medicine, University of Michigan, 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Ryan
authors.affiliation: Department of Psychiatry, School of Medicine, University of Michigan, 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA.|Center for Clinical Management Research (CCMR) Veterans Affairs, Ann Arbor, USA.
authors.forename: Zongshan
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Department of Psychiatry, School of Medicine, University of Michigan, 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA.
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
authors.affiliation: Clinical Pharmacy Department, College of Pharmacy, University of Michigan, 428 Church St, Ann Arbor, MI, 48109-106, USA. vellingr@med.umich.edu.|Department of Psychiatry, School of Medicine, University of Michigan, 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA. vellingr@med.umich.edu.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D002394:Catechol O-Methyltransferase
keywords: Bipolar disorder; COMT; Cognition; Second generation antipsychotic