Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy.
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Genes (Basel). 2022 Mar 9;13(3):482. doi: 10.3390/genes13030482.
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.
冲动性被认为是双相情感障碍（BD）的一种内表型；此外，冲动水平已被证明具有预后意义，并可预测生活质量。迄今为止，关于心境障碍中冲动性的遗传决定因素的报告有限，且没有关于 BD 个体的研究。BD 和健康对照（HC）个体在一项观察性、多中心研究（GECOBIP）中被招募。对三个候选单核苷酸多态性（SNP）（5-HTTLPR、COMT rs4680、BDNF rs6265）进行了基因分型；通过意大利版巴雷特冲动量表（BIS-11）测量冲动性。构建了一个混合效应回归模型，将 BIS 评分作为因变量，三个多态性的基因型作为固定效应，入组中心作为随机效应。与 HC 相比，处于缓解期的 BD 患者的所有 BIS 因子评分均较高（总 BIS 评分的调整β：5.35，p < 0.001）。在任何多态性中，疾病状态（HC 与 BD）和 SNP 状态之间均未显示出显著的相互作用效应。考虑到整个样本，BDNF Met/Met 纯合子与所有三个因素的 BIS 评分降低有关（总 BIS 评分的调整β：-10.2，p < 0.001）。对于 SS 基因型，发现 BDNF 5-HTTLPR x 性别存在显著的相互作用，仅与女性的 BIS 评分升高有关（总 BIS 评分的调整β：12.0，p = 0.001）。最后，COMT 多态性状态与 BIS 评分无显著相关性。总之，在所考虑的三个 SNP 中，BD 诊断均未影响对冲动性评分的影响。只有一个 SNP（BDNF rs6265 Met/Met 纯合子）与较低的冲动性评分独立相关。5-HTTLPR SS 基因型仅与女性的较高冲动性评分有关。需要进一步采用全基因组筛查在更大的样本中研究，以确定 BD 中冲动性的遗传基础。
