Association analysis between gene variants of the tyrosine hydroxylase and the serotonin transporter in borderline personality disorder.

OBJECTIVES: For patients with borderline personality disorder (BPD), we previously reported an independent effect of the catechol-o-methyl-transferase (COMT) low-activity (Met(158)) allele and an interaction with the low-expression allele of the deletion/insertion (short/long or S/L, resp.) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR). The purpose of the present study was to extend these findings to the tyrosine hydroxylase (TH) Val(81)Met single nucleotide polymorphism (SNP), the 5-HTTLPR S/L polymorphism incorporating the recently described functional A/G SNP within the long allele of the 5-HTTLPR (rs25531) as well as the variable number of tandem repeat (VNTR) polymorphism within intron 2 of the serotonin transporter gene (STin2). METHODS: In 156 Caucasian BPD patients and 152 healthy controls, we tested for association between BPD and the TH Val(81)Met SNP, the 5-HTTLPR/rs25531 polymorphism, the STin2, the interaction of the TH Val(81)Met SNP with the tri-allelic 5-HTTLPR/rs25531, the interaction of the TH Val(81)Met SNP with STin2. RESULTS: Between BPD patients and controls, we observed a slight over-representation of the TH Met(81)Met genotype in BPD patients compared to controls, but no statistically significant differences in genotype distribution of the individual markers after adjusting for multiple testing. Logistic regression analysis showed a lack of interaction between the TH Val(81)Met and the 5-HTTLPR/rs25531 as well as between the TH Val(81)Met and the STin2 polymorphism. CONCLUSIONS: These data do not suggest independent or interactive effects of the TH Val(81)Met, the 5-HTTLPR/rs25531, or the STin2 polymorphisms in BPD.

Association analysis of serotonin receptor 1B (HTR1B) and brain-derived neurotrophic factor gene polymorphisms in Borderline personality disorder.

The purpose of this study was to test for association between Borderline personality disorder (BPD) and variants of the HTR1B and the brain-derived neurotrophic factor (BDNF) gene. We genotyped four HTR1B and the functional BDNF G196A marker in 161 Caucasian BPD patients and 156 healthy controls. There were no significant differences between groups in genotype or haplotype distribution of HTR1B markers or in genotype distribution of the BDNF marker. Logistic regression analyses revealed an over-representation of the BDNF 196A allele in HTR1B A-161 allele carrying BPD patients.

Gender differences in axis I and axis II comorbidity in patients with borderline personality disorder.

BACKGROUND/AIMS: Differences in the clinical presentation of men and women with borderline personality disorder (BPD) are of potential interest for investigations into the neurobiology, genetics, natural history, and treatment response of BPD. The purpose of this study was to investigate gender differences in axis I and axis II comorbidity and in diagnostic criteria in BPD patients. METHODS: 110 women and 49 men with BPD were assessed with the computer-based version of the Munich-Composite International Diagnostic Interview and the Structured Clinical Interview for DSM-IV Personality Disorders. Gender differences were investigated for the following outcomes: (a) lifetime, 12-month and 4-week prevalence of axis I disorders; (b) axis II disorders, and (c) DSM-IV BPD diagnostic criteria. RESULTS: With regard to lifetime prevalence of axis I disorders, men more often displayed a substance use disorder, in particular alcohol dependency (65 vs. 43%); on the other hand, women more frequently had an affective (94 vs. 82%), anxiety (92 vs. 80%) or eating disorder (35 vs. 18%), in particular anorexia nervosa (21 vs. 4%). Regarding the 12-month prevalence, we found significantly more women suffering from anorexia nervosa (13 vs. 0%). Considering the 4-week prevalence, there were no significant gender differences. With regard to axis II disorders, men had a higher frequency of antisocial personality disorder (57 vs. 26%). Regarding the BPD diagnostic criteria, men more often displayed 'intensive anger' (74 vs. 49%), whereas women more frequently showed 'affective instability' (94 vs. 82%). CONCLUSION: In this German study, we could replicate and extend the findings from previous US studies, where men and women with BPD showed important differences in their pattern of psychiatric comorbidity. The implications for clinicians and researchers are discussed.

The 5-HTTLPR polymorphism modulates the association of serious life events (SLE) and impulsivity in patients with Borderline Personality Disorder.

BACKGROUND: Impulsivity belongs to the key features of Borderline Personality Disorder (BPD). It has been linked to altered serotoninergic neurotransmission and, genetically, to an over-representation of the short (S) allele of the serotonin transporter promoter-linked polymorphic region polymorphism (5-HTTLPR). On the other hand, serious life events (SLE) are of major importance in the development of BPD. However, the inter-relations between SLEs, impulsivity, and 5-HTTLPR are not understood. METHOD: 159 BPD patients from Germany were included in this study. Impulsivity was assessed by the Barratt Impulsiveness Scale (BIS). We analysed (1) the effects of SLEs on impulsivity; and (2) modulating effects of the 5-HTTLPR polymorphism on the effects of SLEs on impulsivity. RESULTS: Regression analyses confirmed a decreasing effect of childhood sexual abuse, the cumulative SLE-related reactions and the impairment by SLEs on BIS sum score. Regarding BIS sum score, all SLEs except for rape were associated with a decrease of impulsivity in SS/SL carriers and an increase of BIS sum score in LL carriers. CONCLUSIONS: This study analyzing a specific gene x environment interaction in BPD patients suggests an interaction between SLEs and the 5-HTTLPR S/L polymorphism in the development of impulsivity in BPD patients. Clinical and research implications are discussed.

Interaction between gene variants of the serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT) in borderline personality disorder.

Borderline personality disorder (BPD) is characterized by a heterogeneous symptomatology with instability in impulse control, interpersonal relationships and self-image. BPD patients display repeated self-injury, chronic suicidal tendencies and emotional dysregulation, mainly dysregulation of negative affect. In its etiology, genetic and environmental factors have been suggested. Recently, an investigation in male healthy volunteers found gene-gene effects of the catechol-O-methyl-transferase (COMT) low-activity (Met(158)) and the low-expression allele of the deletion/insertion (short/long or S/L, respectively) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR) on the central processing of aversive stimuli. The purpose of the present study was to test for association between BPD and the COMT Val(158)Met single nucleotide polymorphism (SNP), the 5-HTTLPR S/L variant and the interaction of these two gene variants. One hundred sixty one well-defined Caucasian BPD patients and 156 healthy controls were recruited from central Germany. In BPD patients, the genotype COMT Met(158)Met was over-represented compared to healthy controls (P = 0.0085; adjusted P = 0.034). We observed no differences in 5-HTTLPR genotypes between BPD and controls (P = 0.286). Additionally, the COMT Met(158)Met genotype was significantly over-represented in BPD patients carrying at least one 5-HTTLPR S allele (P = 0.0007; adjusted P = 0.028). Logistic regression analysis confirmed an interaction of the COMT Met(158) and the 5-HTTLPR S allele (P = 0.001). These data suggest an involvement of altered dopaminergic and/or noradrenergic neurotransmission as well as an interactive effect of COMT and 5-HTTLPR gene variants in the etiology of BPD, and underline the usefulness of analyses of gene-gene effects in diseases of complex inheritance with multiple genes involved.

Association analysis of SCN9A gene variants with borderline personality disorder.

Borderline personality disorder (BPD) is a serious psychiatric disorder affecting about 1-2% of the general population. Key features of BPD are emotional instability, strong impulsivity, repeated self-injurious behavior (SIB) and dissociation. In the etiology of BPD and its predominant symptoms, genetic factors have been suggested. The voltage-gated sodium channel Nav1.7 is expressed in sensory neurons and in the hippocampus, a key region of the limbic system probably dysfunctional in BPD and dissociative disorders. The alpha-subunit of Nav1.7 is encoded by the SCN9A gene on chromosome 2 and variations of SCN9A can lead to complete inability to sense pain. The aim of the present study was to test for associations between SCN9A gene variants and BPD as well as BPD-related phenotypes. We genotyped ten tagging single nucleotide polymorphisms (SNPs) within the SCN9A gene in 161 well-defined Caucasian BPD patients and 156 healthy controls. We found no globally significant association of SCN9A markers with BPD at level 5%. However, in the female and in the male subsample, different SCN9A markers and individual haplotypes showed uncorrected p-values<0.05. In addition, p-values<0.05 were observed in the analysis of associations between SCN9A markers and dissociative symptoms. Although our results were largely negative, replication studies in an independent sample are warranted to follow up on the potential role of SCN9A gene variants in BPD and dissociative symptoms, paying special attention to a possible gender different etiology.