The serotonin transporter gene polymorphism (5-HTTLPR) and affective symptoms among women diagnosed with borderline personality disorder
Section of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.European Psychiatry (Impact Factor: 3.44). 09/2009; 25(1):19-25. DOI: 10.1016/j.eurpsy.2009.05.001
Gene variants of the serotonin transporter have been associated with vulnerability to affective disorders. In particular, the presence of one or two copies of the short (s) allele of the 5-HTTLPR polymorphism has been associated with reduced serotonin transporter expression and function, and vulnerability to affective disorders. To test for an association between variants of the serotonin transporter gene polymorphism (5-HTTLPR) and relevant clinical features of borderline personality disorder (BPD), a psychiatric disorder with symptoms characteristic for serotonin dysfunction, 77 women with BPD were genotyped in the 5-HTTLPR polymorphism. They rated their subjective experience of borderline-specific, depressive, anxious and obsessive-compulsive symptoms, and were interviewed about lifetime incidence of suicide attempts and self-harming acts. Carriers of two s alleles of the 5-HTTLPR reported more symptoms of borderline, depression, anxiety and obsessive-compulsive behaviours, but not of suicidal and self-injury behaviour, compared to carriers of a long (l) allele. This indicates that the 5-HTTLPR ss homozygous genotype might influence serotonin function affecting susceptibility to both borderline-specific, depressive, anxious and obsessive-compulsive symptoms in BPD, and leading to a more severe symptomatology related to these clinical features. Further, this suggests that 5-HTT gene variants may not be as influential on suicidal and self-injury behaviour in BPD.
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- "Family, adoption and twin studies demonstrate that genetics play a role in suicidal behavior . In fact, the influence of genetic variants on human behavior may be relevant to the symptomatology involved in psychiatric disorders . For instance, genetic variants in the serotonin transporter have been associated with vulnerability to affective disorders. "
ABSTRACT: The aim of the present study was to analyze if the genetic polymorphisms might predict suicide attempts in mental disorder patients. The literature review and meta-analysis were conducted using the PubMed/Medline, Web of science and Scopus database using the terms: "5-HTT or SLC6A4 or 5-SERT and suicide, suicidal ideation or suicidal behavior or suicidal attempt". Thirty articles were analyzed. We found 17 articles that showed association and 13 articles that showed no association between LPR serotonin transporter polymorphism and suicide. A higher study of suicide identified the serotonin transporter polymorphism in patients with schizophrenia, mental disorder, major depression and bipolar disorder. There is an association between the serotonin-transporter-linked polymorphic region and suicidal behavior. The mental disorders with greater relationship with the suicide were the bipolar disorder, major depression and schizophrenia. The L allele had higher risk for suicide.
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- "A number of negative associations between the 5-HTTLPR and suicidality have also been reported (Akar et al., 2010; Segal et al., 2009) in spite of violent attempts or completion being assessed. Another study found no association in a small sample of borderline patients (Maurex et al., 2010). Other studies found null associations but assessed suicidal ideation only (Coventry et al., 2010; Wang et al., 2009), or did not specify the type of suicidal behavior exhibited (Contreras et al., 2010). "
ABSTRACT: Suicide is one of the leading causes of death in the world. Its aetiology is complex and diverse, however, epidemiological studies show that suicidal behavior is partly heritable. Neurobiological evidence implicates serotonergic dysfunction in suicidality, stimulating genetic research to focus on genes related to the serotonergic system. In this paper, we review evidence from studies examining the association between various serotonergic genes (Tryptophan Hydroxylase genes: TPH1; TPH2, Serotonin Transporter gene: 5-HTTLPR in SLC6A4, Serotonin Receptor genes: HTR1A, HTR2A, HTR1B, HTR2C and Monoamine Oxidase A gene: MAOA) and suicidal behavior. The data show associations between variation on the TPH1 gene and 5-HTTLPR gene and violent suicidal behavior in Caucasian populations, with the least inconsistencies. Results are mixed for the TPH2 gene and serotonin receptor genes, but for some genes, studies that include haplotypic analyses or that examine a larger coding region of the genes tend to provide more reliable results. Findings on endophenotypes of suicidality, such as aggression and impulsivity traits, show positive associations for the TPH1, HTR2A, and MAOA genes, but need further replication, since negative associations are also occasionally reported. Since genes can only partially explain suicidal risk, several studies during the past decade have tried to incorporate environmental factors in the susceptibility model. Studies to date show that variation on the 5-HTTLPR, MAOA and HTR2A gene can interact with stressful life events to increase risk for suicidal behavior. Limitations of case-control studies are discussed and future considerations are put forward with regard to endophenotypic measurements and gene-environment interactions.
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- "In addition to homozygous SERT −/− rats and mice (which display overt developmental and behavioral deficits; Holmes et al., 2003b; Homberg et al., 2007; Kalueff et al., 2010; Murphy and Lesch, 2008), SERT +/− rodents also show altered emotional and motor behaviors, as well as increased sensitivity to various experimental manipulations (Ansorge et al., 2004; Fox et al., 2007; Moya et al., 2011; Murphy and Lesch, 2008). Their 50% decrease in transporter activity (Fox et al., 2009; Snoeren et al., 2010) resembles polymorphisms in the human SERT gene (Hu et al., 2006; Lesch et al., 1996; Maurex et al., 2010; Praschak-Rieder et al., 2007), especially the well-studied human SERT-linked promoter region (5HTT-LPR, consisting of the 'active' L allele and the 'less active' S allele), which is strongly implicated in multiple behavioral syndromes (Blom et al., 2011; Kuzelova et al., 2010; Nikolas et al., 2010). BDNF is crucial for various brain processes, including cell differentiation and survival, axonal growth, neurogenesis and memory formation (Acheson et al., 1995; Bekinschtein et al., 2008; Cheng et al., 2011; Pencea et al., 2001), acting via tyrosine kinase B (TrkB) and p75 receptors. "
ABSTRACT: Serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) are key modulators of molecular signaling, cognition and behavior. Although SERT and BDNF mutant mouse phenotypes have been extensively characterized, little is known about their self-grooming behavior. Grooming represents an important behavioral domain sensitive to environmental stimuli and is increasingly used as a model for repetitive behavioral syndromes, such as autism and attention deficit/hyperactivity disorder. The present study used heterozygous ((+/-)) SERT and BDNF male mutant mice on a C57BL/6J background and assessed their spontaneous self-grooming behavior applying both manual and automated techniques. Overall, SERT(+/-) mice displayed a general increase in grooming behavior, as indicated by more grooming bouts and more transitions between specific grooming stages. SERT(+/-) mice also aborted more grooming bouts, but showed generally unaltered activity levels in the observation chamber. In contrast, BDNF(+/-) mice displayed a global reduction in grooming activity, with fewer bouts and transitions between specific grooming stages, altered grooming syntax, as well as hypolocomotion and increased turning behavior. Finally, grooming data collected by manual and automated methods (HomeCageScan) significantly correlated in our experiments, confirming the utility of automated high-throughput quantification of grooming behaviors in various genetic mouse models with increased or decreased grooming phenotypes. Taken together, these findings indicate that mouse self-grooming behavior is a reliable behavioral biomarker of genetic deficits in SERT and BDNF pathways, and can be reliably measured using automated behavior-recognition technology.
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