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.
"Compared with healthy controls, BPD patients were also found to show a reduced serotonin transporter density in the cingulate cortex (Frankle et al., 2005) as well as decreased serotonergic functioning in the hypothalamus (Koch et al., 2007) and in hippocampal regions (Soloff et al., 2007). Heritability accounts for about 50% of aggression (Rhee & Waldman , 2002) and serotonergic genes; a polymorphism of the serotonin transporter gene (Silva et al., 2007) and a haplotype of the tryptophan hydroxylase gene (Perez-Rodriguez et al., 2010) were associated with aggression in BPD patients. However, the identification of a single gene locus with a major effect size on aggression seems unlikely (Craig & Halton, 2009); rather, gene– environment interactions are expected, such as the enhancement of antisocial behavior in subjects with a polymorphism of monoamine oxidase A (MAOA) when exposed to childhood maltreatment (Byrd & Manuck, 2014; Caspi et al., 2002). "
[Show abstract][Hide abstract] ABSTRACT: This article proposes a multidimensional model of aggression in borderline personality disorder (BPD) from the perspective of the biobehavioral dimensions of affective dysregulation, impulsivity, threat hypersensitivity, and empathic functioning. It summarizes data from studies that investigated these biobehavioral dimensions using self-reports, behavioral tasks, neuroimaging, neurochemistry as well as psychophysiology, and identifies the following alterations: (a) affective dysregulation associated with prefrontal-limbic imbalance, enhanced heart rate reactivity, skin conductance, and startle response; (b) impulsivity also associated with prefrontal-limbic imbalance, central serotonergic dysfunction, more electroencephalographic slow wave activity, and reduced P300 amplitude in a 2-tone discrimination task; (c) threat hypersensitivity associated with enhanced perception of anger in ambiguous facial expressions, greater speed and number of reflexive eye movements to angry eyes (shown to be compensated by exogenous oxytocin), enhanced P100 amplitude in response to blends of happy versus angry facial expressions, and prefrontal-limbic imbalance; (d) reduced cognitive empathy associated with reduced activity in the superior temporal sulcus/gyrus and preliminary findings of lower oxytocinergic and higher vasopressinergic activity; and (e) reduced self-other differentiation associated with greater emotional simulation and hyperactivation of the somatosensory cortex. These biobehavioral dimensions can be nicely linked to conceptual terms of the alternative Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) model of BPD, and thus to a multidimensional rather than a traditional categorical approach. (PsycINFO Database Record
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"Serotonergic genetic polymorphisms, mainly related to the serotonin transporter, are associated with disorganized attachment classification in the context of trauma and adverse care-giving environments.17 Despite neurobiological evidence of a disturbance in serotonin signaling associated with BPD and associated phenomena such as impulsivity, aggression, and suicidality,57-69 the clinical significance of these findings in terms of psychopharmacologic enhancement of serotonergic neurotransmission has recently been called into question. In contrast to the 2001 American Psychiatric Association (APA) guidelines for treatment of BPD,70 recent systematic reviews have highlighted a limited role for antidepressants in the treatment of BPD, due to more modest therapeutic effects on these symptom domains relative to other medication classes.23-26,29 "
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: While it is premature to provide a simple model for the vulnerability to the development of either borderline (BPD) or schizotypal (SPD) personality disorder, it is clear that these heritable disorders lend themselves to fruitful neurobiological exploration. The most promising findings in BPD suggest that a diminished top-down control of affective responses, which is likely to relate to deceased responsiveness of specific midline regions of prefrontal cortex, may underlie the affective hyperresponsiveness in this disorder. In addition, genetic and neuroendocrine and molecular neuroimaging findings point to a role for serotonin in this affective disinhibition. Clearly SPD falls within the schizophrenia spectrum, but precisely the nature of what predicts full-blown schizophrenia as opposed to the milder symptoms of SPD is not yet clear.
The Psychiatric clinics of North America 09/2008; 31(3):441-61, vii. DOI:10.1016/j.psc.2008.03.011 · 1.87 Impact Factor
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