title: Cognitive manic symptoms in bipolar disorder associated with polymorphisms in the DAOA and COMT genes.
abstract: BACKGROUND
  Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.
  
  
  METHODS
  Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. [Table: see text].
  
  
  RESULTS
  The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. [Table: see text] [Table: see text].
  
  
  CONCLUSIONS
  Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population.
authors.affiliation: Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. dzana.hukic@ki.se
authors.forename: Dzana Sudic
authors.initials: DS
authors.lastname: Hukic
authors.forename: Louise
authors.initials: L
authors.lastname: Frisén
authors.forename: Lena
authors.initials: L
authors.lastname: Backlund
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
authors.forename: Lil
authors.initials: L
authors.lastname: Träskman-Bendz
authors.forename: Gunnar
authors.initials: G
authors.lastname: Edman
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Urban
authors.initials: U
authors.lastname: Ösby
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D002394:Catechol O-Methyltransferase