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- Title
Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the <i>DAOA</i> and <i>COMT</i> Genes.
- Authors
Hukic, Dzana Sudic; Frisén, Louise; Backlund, Lena; Lavebratt, Catharina; Landén, Mikael; Träskman-Bendz, Lil; Edman, Gunnar; Schalling, Martin; Ösby, Urban
- Abstract
Introduction: 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. Methodology: 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. 10.1371/journal.pone.0067450.t001Table 1 Clinical characteristics of the Bipolar 1 patient sample.: Bipolar disorder type 1 [n] 488 Men [n (%)] 209 (43) Talkativeness [n (%)] 373 (76) Distracibility [n (%)] 269 (55) Thought disorder [n (%)] 372 (76) Cognitive manic symptoms* [n (%)] 215 (44) Men [n (%)] 81 (39) Non-Cognitive manic symptoms [n (%)] 248 (51) Men [n (%)] 117 (56) Unknown [n (%)] 25 (5) Men [n (%)] 11 (44) Anonymous blood donors (ABD) 1044 Men [n (%)] 616 (59) *having all three symptoms: talkativeness, distractibility, and tought disorder. 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. 10.1371/journal.pone.0067450.t002Table 2 Allelic association in bipolar 1 patients with cognitive manic symptoms (CMS) patients compared to non-CMS and to ABD controls in the DAOA and COMT genes.: BP1 CMS BP1 non-CMS ABD BP1 CMS vs. non-CMSb BP1 CMS vs. ABD controlsb Gene SNPa aa/ab/bb aa/ab/bb aa/ab/bb p EMP1c EMP2d OR [95% CI] e p EMP1c EMP2d OR [95% CI] e DAOA rs3916967 (C/T) 32/88/89 50/118/77 177/494/361 0.018 0.018 0.21 0.72 [0.55–0.93] 0.029 0.026 0.28 0.78 [0.66–1.0] DAOA rs2391191 (A/C) 28/75/79 39/111/70 179/487/357 0.055 0.039 0.50 0.75 [0.57–1.0] 0.020 0.019 0.21 0.75 [0.63–1.0] DAOA rs1935062 (C/A) 26/67/89 35/102/86 146/460/405 0.12 0.12 0.78 0.80 [0.58–1.0] 0.069 0.066 0.52 0.80 [0.65–1.0] COMT rs5993883 (T/G) 33/120/53 71/112/57 269/510/223 0.025 0.030 0.27 0.73 [0.56–0.95] 0.0017* 1.0E−4* 0.021* 0.68 [0.91–1.4] COMT rs165599 (G/A) 29/94/87 25/93/126 87/443/501 0.093 0.094 0.69 1.27 [1.0–1.8] 0.014 0.017 0.16 1.34 [1.1–1.7] aSNP (minor allele(a)/major allele(b)).bgender and rs1718119 as covariate.cpoint-wise p-value from 10,000 pemutations with no covarite (EMP1).dcorrected empirical p-value by max (T) permutation.eodds ratio (OR), the proportion of minor versus major allele affected (cognitive manic symptoms factor)/proportion of minor versus major allele unaffected (non-cognitive manic symptoms factor or ABD controls).*significant after correction for multiple testing by max (T) permutation.10.1371/journal.pone.0067450.t003Table 3 Haplotype association of haplotype group
- Publication
PLoS ONE, 2013, Vol 8, Issue 7, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0067450