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

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          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.

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          Factor structure of the barratt impulsiveness scale

          The purpose of the present study was to revise the Barratt Impulsiveness Scale Version 10 (BIS-10), identify the factor structure of the items among normals, and compare their scores on the revised form (BIS-11) with psychiatric inpatients and prison inmates. The scale was administered to 412 college undergraduates, 248 psychiatric inpatients, and 73 male prison inmates. Exploratory principal components analysis of the items identified six primary factors and three second-order factors. The three second-order factors were labeled Attentional Impulsiveness, Motor Impulsiveness, and Nonplanning Impulsiveness. Two of the three second-order factors identified in the BIS-11 were consistent with those proposed by Barratt (1985), but no cognitive impulsiveness component was identified per se. The results of the present study suggest that the total score of the BIS-11 is an internally consistent measure of impulsiveness and has potential clinical utility for measuring impulsiveness among selected patient and inmate populations.
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            The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function

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              Bipolar disorder.

              Bipolar disorder is a recurrent chronic disorder characterised by fluctuations in mood state and energy. It affects more than 1% of the world's population irrespective of nationality, ethnic origin, or socioeconomic status. Bipolar disorder is one of the main causes of disability among young people, leading to cognitive and functional impairment and raised mortality, particularly death by suicide. A high prevalence of psychiatric and medical comorbidities is typical in affected individuals. Accurate diagnosis of bipolar disorder is difficult in clinical practice because onset is most commonly a depressive episode and looks similar to unipolar depression. Moreover, there are currently no valid biomarkers for the disorder. Therefore, the role of clinical assessment remains key. Detection of hypomanic periods and longitudinal assessment are crucial to differentiate bipolar disorder from other conditions. Current knowledge of the evolving pharmacological and psychological strategies in bipolar disorder is of utmost importance.
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                Journal
                GENEG9
                Genes
                Genes
                MDPI AG
                2073-4425
                March 2022
                March 09 2022
                : 13
                : 3
                : 482
                Article
                10.3390/genes13030482
                35328036
                879dc0ca-fdf2-4de8-8845-91e2966288db
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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