Genetics of borderline personality disorder: systematic review and proposal of an integrative model.
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.
Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France; Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université Droit & Santé Lille (UDSL), F-59000 Lille, France; Psychiatry and Pediatric Psychiatry Department, University Medical Centre of Lille (CHULille), F-59037 Lille, France. Electronic address: ali.amad@chru-lille.fr.
Ali
A
Amad
INSERM U894, Centre de Psychiatrie & Neurosciences, Paris, France.
Nicolas
N
Ramoz
Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France; Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université Droit & Santé Lille (UDSL), F-59000 Lille, France; Psychiatry and Pediatric Psychiatry Department, University Medical Centre of Lille (CHULille), F-59037 Lille, France.
Pierre
P
Thomas
Univ Lille Nord de France, CHRU de Lille, F-59000 Lille, France; Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université Droit & Santé Lille (UDSL), F-59000 Lille, France; Psychiatry and Pediatric Psychiatry Department, University Medical Centre of Lille (CHULille), F-59037 Lille, France.
Renaud
R
Jardri
INSERM U894, Centre de Psychiatrie & Neurosciences, Paris, France; Sainte-Anne Hospital (Paris-Descartes University), Paris, France.
Philip
P
Gorwood
D000818:Animals; D001883:Borderline Personality Disorder / Q000235:genetics*; D002394:Catechol O-Methyltransferase; D016208:Databases, Factual / Q000706:statistics & numerical data; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005823:Genetics; D006801:Humans; D012701:Serotonin / Q000235:genetics / Q000378:metabolism
D012701:Serotonin; D002394:Catechol O-Methyltransferase; D004298:Dopamine
Borderline personality disorder; Genetics; Gene–environment interaction; Plasticity genes