New developments in the genetics of borderline personality disorder

Abstract

ContextThe etiology of borderline personality disorder (BPD) is complex. Patients with BPD report many negative events during childhood, such as neglect, sexual abuse, and physical abuse. However, none of these antecedents is considered specific to BPD. Interestingly, a genetic vulnerability has been identified in patients with BPD, and there is a recent interest in the potential interaction between genetic and psychosocial factors (e.g., childhood abuse) in BPD.ObjectiveWe propose here a review of the current literature concerning the genetics of BPD and recommendations for future research.DiscussionHere are several explanations that may account for this lack of results. One of them may be due to the choice of candidate genes. Indeed, there is a tendency to look for genetic effects on disease rather than genetic effects on vulnerability to environmental causes of disease. We believe that such a conceptual shift may affect the choice of new candidate genes in BPD. Genes associated with the physiological response to stress in the hypothalamic–pituitary–adrenal axis are then natural candidates for gene–environment interactions research in BPD. Finally, we propose a paradigm shift, in which “plasticity” genes (rather than “vulnerability” genes) would be involved in the pathogenesis of BPD.ConclusionFamilial and twin studies largely support the potential role of a genetic vulnerability at the root of BPD, with an estimated heritability of approximately 40%. Moreover, there is evidence for both gene–environment interactions and correlations. However, association studies for BPD are sparse, making it difficult to draw clear conclusions. According to our meta-analysis, no significant associations were found.