Nature and nurture? A review of the literature on childhood maltreatment and genetic factors in the pathogenesis of borderline personality disorder

J Psychiatr Res. 2021 May:137:131-146. doi: 10.1016/j.jpsychires.2020.12.025. Epub 2020 Dec 11.

Abstract

Background: Borderline Personality Disorder (BPD) is a psychiatric disorder associated with significant morbidity and mortality. However, the neurobiological alterations underlying the condition remain poorly understood. As a result, existing treatments remain inadequate. One of the main risk factors for the development of BPD is a history of childhood maltreatment. However, it is considered neither causative nor specific to the condition. Current theory is therefore increasingly moving toward a 'Gene x Environment' (GxE) model of the condition. The purpose of the current work was to conduct a systematic literature review, which comprehensively identifies all published molecular level GxE studies that have explored the role of specific genetic loci, in influencing the risk of BPD following exposure to childhood abuse or neglect.

Methods: Four electronic databases were used to systematically search for molecular level GxE studies of any design, which focused on the development of BPD following exposure to childhood abuse or neglect, without language or date restrictions. Articles were screened independently by two reviewers and results were synthesized narratively.

Results: A total of 473 articles were screened of which sixteen were selected for inclusion in our review. Implicated genes were categorised according to their influence on; Neurotransmitter Systems, Neurodevelopment and Neuroendocrine Systems.

Conclusions: The identified studies have produced several relevant and statistically significant results. Of particular note, is the repeated finding that genes involved in HPA axis regulation, may be altered by exposure to childhood maltreatment, influencing subsequent susceptibility to BPD. This is both biologically plausible and of potential clinical significance.

Keywords: Adverse childhood experiences; Borderline personality disorder; Child abuse; Child neglect; Epigenetic modifications; Genetic markers.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Borderline Personality Disorder* / genetics
  • Child
  • Child Abuse*
  • Humans
  • Hypothalamo-Hypophyseal System
  • Pituitary-Adrenal System
  • Risk Factors