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 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.
Highlights
Bipolar disorder (BD) is a severe, chronic, and common mental illness, characterized by episodes of elevated mood alternating with depressive episodes [1]
There were no significant differences in BIS scores between different COMT genotypes (Figure 1); significant differences in BIS scores were found for the 5-HTTLPR and BDNF
We found that the effect of 5-HTTLPR polymorphism on impulsivity was dependent on gender, with the SS genotype associated with higher impulsivity levels across all the BIS-1 factors in females, but not in males
Summary
Bipolar disorder (BD) is a severe, chronic, and common mental illness, characterized by episodes of elevated mood (hypomania or mania) alternating with depressive episodes [1]. While mood changes represent the defining feature of the disease, individuals with BD display various mood-independent trait patterns encompassing temperament, character, and personality [4–9]. Impulsivity is one psychological dimension that has been shown to be significantly represented in individuals with BD [10–12], even during a phase of euthymia [13,14]; trait impulsivity is increased in unaffected relatives of individuals with BD [15]. Impulsivity is defined as “a predisposition towards rapid, unplanned reactions to internal or external stimuli without regard to the negative consequences of these reactions to the impulsive individual or others” [18] and in BD individuals is associated with at-risk behaviors, such as suicidality, substance abuse and criminal actions [11,19]; it is a predictor of quality of life [20], disease onset [21] and illness severity [13]
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