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-Omethyl-transferase (COMT) low-activity (Met 158 ) and the lowexpression allele of the deletion/insertion (short/long or S/L, respectively) polymorphism in the serotonin transporterlinked 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 ¼ 0.0085; adjusted P ¼ 0.034). We observed no differences in 5-HTTLPR genotypes between BPD and controls (P ¼ 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 ¼ 0.0007; adjusted P ¼ 0.028). Logistic regression analysis confirmed an interaction of the COMT Met 158 and the 5-HTTLPR S allele (P ¼ 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.

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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.

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