Serotonin transporter polymorphism and fluoxetine effect on impulsiveness and aggression in borderline personality disorder.
ABSTRACT Impulsiveness and aggressiveness are characteristics of borderline personality disorder and are associated to a serotoninergic system dysfunction. Serotonin transporter polymorphisms have been linked to aggressive and impulsive behaviors. The short allele (S) in depression is associated to a worse response to selective serotonin reuptake inhibitors (SSRI). This study aims to study these polymorphisms to predict the response of aggressive and impulsive behaviors to SSRIs in borderline personality disorder.
Fifty-nine patients with DSM-IV borderline personality disorder in accordance with the International Personality Disorder Examination (IPDE) and without axis 1 disease were treated with flexible doses of fluoxetine for 12 weeks. The patients were evaluated with the Overt Aggression Scale Modified (OAS-M) at the beginning and at 2, 4, 8 and 12 weeks of treatment. Polymorphisms L and S of the serotonin transporter promoter region were determined. Response to fluoxetine of the LL carriers versus the S carriers (LS+SS) was compared.
LL carriers had a better response than S carriers in the reduction of total OAS-M scores and on the aggressiveness and irritability components of the OAS-M.
L-allele carriers responded better to fluoxetine than S carriers, in a similar way as in depression. The S allele may represent a common factor of bad response to SSRI in diseases associated to serotoninergic system dysfunction.
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ABSTRACT: Borderline personality disorder (BPD) is one of the most common mental disorders and is characterized by a pervasive pattern of emotional lability, impulsivity, interpersonal difficulties, identity disturbances, and disturbed cognition. Here, we performed a systematic review of the literature concerning the genetics of BPD, including familial and twin studies, association studies, and gene-environment interaction studies. Moreover, meta-analyses were performed when at least two case-control studies testing the same polymorphism were available. For each gene variant, a pooled odds ratio (OR) was calculated using fixed or random effects models. Familial and twin studies largely support the potential role of a genetic vulnerability at the root of BPD, with an estimated heritability of approximately 40%. Moreover, there is evidence for both gene-environment interactions and correlations. However, association studies for BPD are sparse, making it difficult to draw clear conclusions. According to our meta-analysis, no significant associations were found for the serotonin transporter gene, the tryptophan hydroxylase 1 gene, or the serotonin 1B receptor gene. We hypothesize that such a discrepancy (negative association studies but high heritability of the disorder) could be understandable through a paradigm shift, in which "plasticity" genes (rather than "vulnerability" genes) would be involved. Such a framework postulates a balance between positive and negative events, which interact with plasticity genes in the genesis of BPD.Neuroscience & Biobehavioral Reviews 03/2014; 40:6-19. DOI:10.1016/j.neubiorev.2014.01.003 · 10.28 Impact Factor
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ABSTRACT: The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning.06/2013; 15(2):213-24.
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ABSTRACT: Borderline personality disorder (BPD) is a highly prevalent psychiatric disorder with high morbidity and mortality. Early theories ascribed an environmental etiology of BPD, but growing evidence supports a genetic vulnerability as well. The primary aim of this study was to systematically review genetic association studies focused on BPD. PubMed, ISI Web of Knowledge and PsycINFO databases were searched for studies published until December 2012. Meta-analyses were also performed when three or more studies reported genetic data on the same polymorphism. Data were analyzed with Cochrane Collaboration Review Manager Software (RevMan, version 5.0). Quality and publication bias were assessed. The systematic review of association studies examining genetic polymorphisms and BPD produced conflicting results. Meta-analyses were performed for three serotonergic polymorphisms: two common polymorphisms of the serotonin transporter gene (SLC6A4), the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR), and the rs1800532 (A218C) polymorphism of the tryptophan hydroxylase 1 gene (TPH1), all showing no association. No direct role of genetic polymorphisms was found in BPD. However, a few studies only are present in literature to draw definite conclusions. Further studies focusing on gene × gene and gene × environment interactions are needed to more deeply dissect the genetic role in the modulation of BPD.Journal of Psychiatric Research 06/2013; DOI:10.1016/j.jpsychires.2013.06.002 · 4.09 Impact Factor