Genetics of borderline personality disorder: systematic review and proposal of an integrative model

Neurosci Biobehav Rev. 2014 Mar;40:6-19. doi: 10.1016/j.neubiorev.2014.01.003. Epub 2014 Jan 20.


Borderline personality disorder (BPD) is one of the most common mental disorders and is characterized by a pervasive pattern of emotional lability, impulsivity, interpersonal difficulties, identity disturbances, and disturbed cognition. Here, we performed a systematic review of the literature concerning the genetics of BPD, including familial and twin studies, association studies, and gene-environment interaction studies. Moreover, meta-analyses were performed when at least two case-control studies testing the same polymorphism were available. For each gene variant, a pooled odds ratio (OR) was calculated using fixed or random effects models. Familial 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 for the serotonin transporter gene, the tryptophan hydroxylase 1 gene, or the serotonin 1B receptor gene. We hypothesize that such a discrepancy (negative association studies but high heritability of the disorder) could be understandable through a paradigm shift, in which "plasticity" genes (rather than "vulnerability" genes) would be involved. Such a framework postulates a balance between positive and negative events, which interact with plasticity genes in the genesis of BPD.

Keywords: Borderline personality disorder; Genetics; Gene–environment interaction; Plasticity genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Borderline Personality Disorder / genetics*
  • Catechol O-Methyltransferase
  • Databases, Factual / statistics & numerical data
  • Dopamine / genetics
  • Dopamine / metabolism
  • Gene-Environment Interaction*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetics*
  • Humans
  • Serotonin / genetics
  • Serotonin / metabolism


  • Serotonin
  • Catechol O-Methyltransferase
  • Dopamine