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Influences of COMT and 5-HTTLPR polymorphisms on cognitive flexibility in healthy women: inhibition of prepotent responses and memory updating.

ABSTRACT: Understanding genetic factors that affect monoamine neurotransmitters flux in prefrontal cortex may help to further specify the complex neurobiological processes that underlie cognitive function and dysfunction in health and illness. The current study examined the associations between the polymorphisms of dopaminergic (COMT Met158Val) and serotoninergic (5-HTTLPR) genes and the sequential pattern of responses in a motor random generation task providing well-established indexes for executive functioning in a large sample of 255 healthy women. Participants homozygous for the Met allele of the COMT polymorphism showed impaired inhibition of prepotent responses, whereas individuals homozygous for the s-allele of the 5-HTTLPR showed a restricted ability to update information in working memory. Taken together the results indicate differentiated influences of dopaminergic and serotonergic genes on important and definite executive sub-processes related to cognitive flexibility.

SUBMITTER: Weiss EM

PROVIDER: S-EPMC3896383 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Influences of COMT and 5-HTTLPR polymorphisms on cognitive flexibility in healthy women: inhibition of prepotent responses and memory updating.

Weiss Elisabeth M EM Schulter Günter G Fink Andreas A Reiser Eva M EM Mittenecker Erich E Niederstätter Harald H Nagl Simone S Parson Walther W Papousek Ilona I

PloS one 20140120 1

Understanding genetic factors that affect monoamine neurotransmitters flux in prefrontal cortex may help to further specify the complex neurobiological processes that underlie cognitive function and dysfunction in health and illness. The current study examined the associations between the polymorphisms of dopaminergic (COMT Met158Val) and serotoninergic (5-HTTLPR) genes and the sequential pattern of responses in a motor random generation task providing well-established indexes for executive func ...[more]

PMID: 24465579

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Project description:Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP—the BDNF rs6265 Met/Met homozygosis—was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Dataset Information

Influences of COMT and 5-HTTLPR polymorphisms on cognitive flexibility in healthy women: inhibition of prepotent responses and memory updating.

Publications

Influences of COMT and 5-HTTLPR polymorphisms on cognitive flexibility in healthy women: inhibition of prepotent responses and memory updating.

Similar Datasets

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