The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder.

Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

Long-Term Course of Borderline Personality Disorder: A Prospective 10-Year Follow-Up Study.

The aim of this prospective study was to expand previously reported evidence on the 10-year clinical and functional course of borderline personality disorder (BPD) in a Spanish sample. Participants diagnosed with BPD were assessed at baseline and at 10-year follow-up to evaluate BPD symptomatology and other relevant clinical measures, suicidal behavior, dimensional personality traits, Axis I and II comorbidity, use of mental health resources, and psychosocial functioning. At the 10-year follow up, significant improvements were observed on BPD domains, suicidal behavior, and other clinical measures. Neuroticism, impulsiveness, and aggression-hostility features trended toward normalization, whereas activity and sociability were impaired over time. Comorbidity with Axis I and personality disorders remained high. Social functioning and occupational functioning were largely unchanged. These findings confirm the tendency toward a symptomatic remission of BPD over the long term with regard to symptom criteria and characteristic dimensional traits. However, psychosocial functioning remains impaired.

An exploratory association study of the influence of noradrenergic genes and childhood trauma in Borderline Personality Disorder.

This study investigated the possible association of 40 polymorphisms within 4 noradrenergic genes with BPD risk and the modulating effect of childhood trauma on these associations in 481 BPD subjects and 442 controls. COMT rs5993882, DBH rs77905 and SLC6A2 rs1814270 showed associations with BPD, which were modulated by childhood trauma. However, none of these findings survived Bonferroni correction. Further investigation is needed to clarify the involvement of these genes in BPD pathogenesis.