title: The dopamine D3 receptor gene and posttraumatic stress disorder.
abstract: The dopamine D3 receptor (DRD3) gene has been implicated in schizophrenia, autism, and substance use-disorders and is related to emotion reactivity, executive functioning, and stress-responding, processes impaired in posttraumatic stress disorder (PTSD). The aim of this candidate gene study was to evaluate DRD3 polymorphisms for association with PTSD. The discovery sample was trauma-exposed White, non-Hispanic U.S. veterans and their trauma-exposed intimate partners (N = 491); 60.3% met criteria for lifetime PTSD. The replication sample was 601 trauma-exposed African American participants living in Detroit, Michigan; 23.6% met criteria for lifetime PTSD. Genotyping was based on high-density bead chips. In the discovery sample, 4 single nucleotide polymorphisms (SNPs), rs2134655, rs201252087, rs4646996, and rs9868039, showed evidence of association with PTSD and withstood correction for multiple testing. The minor alleles were associated with reduced risk for PTSD (OR range = 0.59 to 0.69). In the replication sample, rs2251177, located 149 base pairs away from the most significant SNP in the discovery sample, was nominally associated with PTSD in men (OR = 0.32). Although the precise role of the D3 receptor in PTSD is not yet known, its role in executive functioning and emotional reactivity, and the sensitivity of the dopamine system to environmental stressors could potentially explain this association.
authors.affiliation: National Center for PTSD at VA Boston Healthcare System, Boston, Massachusetts, USA; Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Wolf
authors.forename: Karen S
authors.initials: KS
authors.lastname: Mitchell
authors.forename: Mark W
authors.initials: MW
authors.lastname: Logue
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Baldwin
authors.forename: Annemarie F
authors.initials: AF
authors.lastname: Reardon
authors.forename: Alison
authors.initials: A
authors.lastname: Aiello
authors.forename: Sandro
authors.initials: S
authors.lastname: Galea
authors.forename: Karestan C
authors.initials: KC
authors.lastname: Koenen
authors.forename: Monica
authors.initials: M
authors.lastname: Uddin
authors.forename: Derek
authors.initials: D
authors.lastname: Wildman
authors.forename: Mark W
authors.initials: MW
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012737:Sex Factors; D018454:Spouses / Q000523:psychology; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D014481:United States; D014728:Veterans / Q000523:psychology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D050637:Receptors, Dopamine D3