Cognitive manic symptoms in bipolar disorder associated with polymorphisms in the DAOA and COMT genes.
Cognitive manic symptoms in bipolar disorder associated with polymorphisms in the DAOA and COMT genes.
复制标题
DOI：
10.1371/journal.pone.0067450
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ösby U
中科院分区：
文献类型：
--
作者：
Hukic DS;Frisén L;Backlund L;Lavebratt C;Landén M;Träskman-Bendz L;Edman G;Schalling M;Ösby U
双相情感障碍的特征是严重的情绪症状，包括严重的抑郁和躁狂发作。在躁狂发作期间，许多患者表现出认知功能障碍。多巴胺和谷氨酸对于认知加工是重要的，因此调节这些神经递质表达的COMT和DAOA基因对于认知功能的研究是感兴趣的。集中在最严重的躁狂发作，一个因素被发现与健谈，注意力分散，思维障碍的综合症状，被认为是认知躁狂症状（CMS）的因素。488例患者进行了基因分型，其中373例（76%）有多话，269例（55%）注意力分散，372例（76%）思维障碍。215例（44%）患者对所有三种症状均呈阳性，因此显示CMS（表1）。作为人群对照，使用了1，044名匿名献血者（ABD）。采用病例-病例和病例-对照设计模型研究双相1型障碍认知躁狂症状与COMT和DAOA基因SNP之间的遗传关联。具有所有三种症状：多话、注意力不集中和智力障碍。这项研究的发现是，双相1型障碍患者的认知躁狂症状与DAOA和COMT基因的遗传变异有关。在等位基因（表2）和单倍型（表3）分析中，发现DAOA SNP和COMT SNP与双相1型障碍认知症状因子的名义相关性。基因型关联分析也支持我们的发现。然而，当CMS患者与ABD对照组进行比较时，只有一种关联在通过max（T）排列进行多重检验的校正中幸存下来。数据还表明，在病例对照模型中，DAOA中的SNP rs 2391191和COMT中的SNP rs 5993883之间存在相互作用。SNP（次要等位基因（a）/主要等位基因（B））。性别和rs 1718119作为协变量。无协变量的10，000个pemutations的逐点p值（EMP 1）。通过max（T）置换校正经验p值。优势比（OR），受影响的次要等位基因与主要等位基因的比例（认知躁狂症状因子）/未受影响的次要等位基因与主要等位基因的比例（非认知躁狂症状因子或ABD对照）。通过max（T）排列进行多重检验校正后显著。频率（F）在样本中。性别和rs 1718119作为协变量。每种单倍型的优势比（OR）。识别与认知功能相关的基因对评估预后和进展具有临床意义。我们的发现与其他研究一致，这些研究表明COMT和DAOA基因与精神疾病和普通人群中认知受损之间存在遗传关联。
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. 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. having all three symptoms: talkativeness, distractibility, and tought disorder. 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. SNP (minor allele(a)/major allele(b)). gender and rs1718119 as covariate. point-wise p-value from 10,000 pemutations with no covarite (EMP1). corrected empirical p-value by max (T) permutation. odds 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. frequency (F) in sample. gender and rs1718119 as covariates. odds ratios (OR) for each haplotype. 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.
登录
查看更多内容
DOI：
10.1073/pnas.111134598
发表时间：
2001-06-05
影响因子：
11.1
作者：
Egan, MF;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
5.4
作者：
Backlund, Lena;Nikamo, Pernilla;Osby, Urban
通讯作者：
Osby, Urban
影响因子：
11
作者：
Chen, YS;Akula, N;McMahon, FJ
通讯作者：
McMahon, FJ
影响因子：
6.7
作者：
Ekman, C. J.;Lind, J.;Landen, M.
通讯作者：
Landen, M.
DOI：
10.1002/ajmg.b.30904
发表时间：
2009-10-05
影响因子：
2.8
作者：
Gomez, Lissette;Wigg, Karen;Barr, Cathy L.
通讯作者：
Barr, Cathy L.