Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the DAOA and COMT Genes期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the DAOA and COMT Genes

Authors:	Dzana Sudic Hukic Louise Frisén Lena Backlund Catharina Lavebratt Mikael Landén Lil Tr?skman-Bendz Gunnar Edman Martin Schalling Urban ?sby

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 (
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)

Open in a separate window^*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 (

BP1 CMS

BP1 non-CMS

ABD

BP1 CMS vs. non-CMS^b

BP1 CMS vs. ABD controls^b

Gene

SNP^a

aa/ab/bb

EMP1^c

EMP2^d

OR [95% CI] ^e

EMP1^c

EMP2^d

OR [95% CI] ^e

DAOA

rs3916967 (C/T)

32/88/89

50/118/77

177/494/361

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

0.78

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]

Open in a separate window^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.

Table 3

Haplotype association of haplotype group 1 in bipolar 1 patients with cognitive manic symptoms (CMS) compared with non-CMS patients or ABD controls in the DAOA gene.

				CMS vs non-CMS^b			CMS vs ABD^b
DAOA	rs3916967	rs2391191	rs1935062	F^a	p	OR [95% CI]^c	F^a	p	OR [95% CI]^c
Haplotype 1	C	A	C	0.32	0.25	0.83 [0.66–1.1]	0.33	0.14	0.83 [0.71–1.1]
Haplotype 2	T	G	C	0.032	0.34	0.64 [0.32–1.1]	0.037	0.19	0.58 [0.37–1.1]
Haplotype 3	C	A	A	0.074	0.077	0.58 [0.39–0.89]	0.075	0.10	0.65 [0.47–1.0]
Haplotype 4	T	G	A	0.57	0.029	1.38 [1.17–1.8]	0.56	0.0057	1.41 [1.1–1.6]

Open in a separate window^afrequency (F) in sample.^bgender and rs1718119 as covariates.^codds ratios (OR) for each haplotype.

Conclusion

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. Keywords:

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Introduction

Methodology

Results

Table 3

Conclusion