Introduction: Borderline personality disorder (BPD) is a severe disorder with high morbidity and mortality, but unknown etiology. Childhood abuse has been proposed as an etiological factor, but the mechanism by which an abuse history could influence the risk for BPD has not been determined. The aim of this study was to determine whether the tryptophan hydroxylase 1 (TPH1) gene is related to BPD in a clinical sample, and whether TPH1 genotypes or haplotypes moderate the relationship between abuse history and BPD.
Methods: Three hundred and ninety-eight patients diagnosed with mood disorders were genotyped for TPH1 G-6526A promoter polymorphism (rs4537731) and the A218C intron 7 polymorphism (rs1800532) and a set of ancestry informative markers, assessed for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnoses, and assessed for a history of physical and sexual abuse.
Results: Patients with a diagnosis of BPD were more likely to be risk allele carriers (A alleles at both loci) than the non-BPD group. Logistic regression analysis predicting BPD diagnosis with both single-nucleotide polymorphisms and haplotypes showed significant interaction effects between genotype and abuse history. Poisson regression predicting the number of BPD diagnostic criteria met with the same predictor set also included a significant interaction term. Risk allele carriers with a history of abuse had an increased likelihood of a BPD diagnosis.
Conclusion: Variation in TPH1may increase risk for developing BPD as a result of childhood abuse. Elements of BPD pathology may be due in part to a genetically influenced serotonergic dysfunction, which in turn may lead to a differential response to environmental stressors.
aDivision of Molecular Imaging and Neuropathology, New York State Psychiatric Institute
bDepartment of Psychiatry, Columbia University College of Physicians and Surgeons
cDepartment of Psychology, City University of New York, John Jay College
dDepartment of Psychiatry, University of Pittsburg Medical Center
eLaboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, New York, New York, USA
Correspondence to Dr Scott T. Wilson, PhD, Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Unit 42, 1051 Riverside Drive, New York, NY 10032, USA Tel: +1 212 543 6236; fax: +1 212 543 6946; e-mail: firstname.lastname@example.org
Received August 16, 2010
Accepted July 14, 2011