Association between dopaminergic polymorphisms and borderline personality traits among at-risk young adults and psychiatric inpatients.
BACKGROUND
In the development of borderline personality disorder (BPD) both genetic and environmental factors have important roles. The characteristic affective disturbance and impulsive aggression are linked to imbalances in the central serotonin system, and most of the genetic association studies focused on serotonergic candidate genes. However, the efficacy of dopamine D2 receptor (DRD2) blocking antipsychotic drugs in BPD treatment also suggests involvement of the dopamine system in the neurobiology of BPD.


METHODS
In the present study we tested the dopamine dysfunction hypothesis of impulsive self- and other-damaging behaviors: borderline and antisocial traits were assessed by Structured Clinical Interview for Diagnosis (SCID) for DSM-IV in a community-based US sample of 99 young adults from low-to-moderate income families. For the BPD trait analyses a second, independent group was used consisting of 136 Hungarian patients with bipolar or major depressive disorder filling out self-report SCID-II Screen questionnaire. In the genetic association analyses the previously indicated polymorphisms of the catechol-O-methyl-transferase (COMT Val158Met) and dopamine transporter (DAT1 40 bp VNTR) were studied. In addition, candidate polymorphisms of the DRD2 and DRD4 dopamine receptor genes were selected from the impulsive behavior literature.


RESULTS
The DRD2 TaqI B1-allele and A1-allele were associated with borderline traits in the young adult sample (p = 0.001, and p = 0.005, respectively). Also, the DRD4 -616 CC genotype appeared as a risk factor (p = 0.02). With severity of abuse accounted for in the model, genetic effects of the DRD2 and DRD4 polymorphisms were still significant (DRD2 TaqIB: p = 0.001, DRD2 TaqIA: p = 0.008, DRD4 -616 C/G: p = 0.002). Only the DRD4 promoter finding was replicated in the independent sample of psychiatric inpatients (p = 0.007). No association was found with the COMT and DAT1 polymorphisms.


CONCLUSIONS
Our results of the two independent samples suggest a possible involvement of the DRD4 -616 C/G promoter variant in the development of BPD traits. In addition, an association of the DRD2 genetic polymorphisms with impulsive self-damaging behaviors was also demonstrated.
Nemoda
Zsofia
Z
Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary. zsofia.nemoda@eok.sote.hu
Lyons-Ruth
Karlen
K
Szekely
Anna
A
Bertha
Eszter
E
Faludi
Gabor
G
Sasvari-Szekely
Maria
M
D000293:Adolescent; D001883:Borderline Personality Disorder / Q000175:diagnosis* / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D038622:Internationality; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011567:Psychiatric Department, Hospital; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000502:physiology; D050638:Receptors, Dopamine D4 / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D055815:Young Adult
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4