TORNA ALL’ELENCO

The Influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 Polymorphisms on Impulsivity in Bipolar Disorder: The Role of Gender in Genes

2022
ASL Alessandria

Tipo pubblicazione

Article

Autori/Collaboratori (20)Vedi tutti...

Boscutti A
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Pigoni A
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy
Delvecchio G
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy

et alii...

Abstract

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 ? 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 ? 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 ? 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.

PMID : 35328036

DOI : 10.3390/genes13030482

Keywords

nucleic acid technique kit; PCR assay kit; TaqMan; brain derived neurotrophic factor; genomic DNA; serotonin transporter; adult; aged; article; Barratt Impulsiveness Scale; bipolar disorder; case control study; cognitive defect; controlled study; DNA extraction; female; gender; gene frequency; genetic polymorphism; genetic variability; genotype; genotyping; heterozygosity; homozygosity; human; impulsiveness; male; observational study; prevalence; psychometry; quality of life; questionnaire; real time polymerase chain reaction; retrospective study; single nucleotide polymorphism; Structured Clinical Interview for DSM Disorders; TaqMan;