ABSTRACT
BACKGROUND: Variations in genes related to the dopaminergic pathway have been implicated in neuropsychiatric disorders such as schizophrenia, substance misuse, Alzheimer's disease and Post Traumatic Stress Disorder (PTSD). A single nucleotide polymorphism (SNP) (957C>T) and a deletion polymorphism (-141delC) in the DRD2 gene and a SNP (Taq1A) in a gene directly downstream of DRD2 have all been implicated in dopamine functioning in the brain. METHODS: To test the importance of these three polymorphisms in PTSD susceptibility, a genetic screen was performed in 127 war veterans diagnosed with PTSD and 228 control individuals without a history of PTSD. RESULTS: No significant association was found between PTSD and the Taq1A or -141delC polymorphisms. However, a significant association was observed with PTSD and the 957C>T polymorphism. PTSD individuals were more likely to carry the C allele compared to the controls (P=0.021). CONCLUSIONS: Our findings suggest that the 957C>T polymorphism in the DRD2 gene is one of the genetic factors for susceptibility to PTSD.
Subject(s)
Alleles , Combat Disorders/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Dopamine D2/genetics , Veterans/psychology , Adult , Australia , Combat Disorders/diagnosis , Combat Disorders/psychology , Gene Frequency/genetics , Genetic Testing , Genotype , Humans , Male , Phenotype , Vietnam ConflictABSTRACT
OBJECTIVE: To identify clusters of patients with post-traumatic stress disorder (PTSD) according to symptom profile and to examine the association of the A1 allele of the D2 dopamine receptor (DRD2) gene with these clusters. METHOD: Fifty-seven untreated Caucasian Vietnam veterans with PTSD were administered the General Health Questionnaire-28 (GHQ) and the Mississippi Scale for combat-related PTSD. DRD2 allelic status was determined by PCR. RESULTS: Subjects with the DRD2 Al allele compared to those without this allele had significantly higher scores on GHQ 2 (anxiety/insomnia), GHQ 3 (social dysfunction) and GHQ 4 (depression). Cluster analysis of the GHQ data identified two primary groups. A high psychopathology cluster (cluster 3), featured by high co-morbid levels of somatic concerns, anxiety/insomnia, social dysfunction and depression, and a low psychopathology cluster (cluster 1), manifested by the reverse pattern. Scores in each of the four GHQ groups were significantly higher in cluster 3 than cluster 1, as was Mississippi Scale PTSD score. DRD2 A1 allele veterans compared to those without this allele were significantly more likely to be found in the high than the low psychopathology cluster group. CONCLUSIONS: DRD2 variants are associated with severe co-morbid psychopathology in PTSD subjects.
Subject(s)
Anxiety Disorders/genetics , Depressive Disorder/genetics , Receptors, Dopamine D2/genetics , Social Behavior Disorders/genetics , Stress Disorders, Post-Traumatic/genetics , Veterans/psychology , Alleles , Analysis of Variance , Anxiety Disorders/epidemiology , Australia/epidemiology , Cluster Analysis , Comorbidity , Depressive Disorder/epidemiology , Genetic Predisposition to Disease/genetics , Genetic Predisposition to Disease/psychology , Humans , Male , Middle Aged , Polymerase Chain Reaction , Psychiatric Status Rating Scales , Severity of Illness Index , Social Behavior Disorders/epidemiology , Stress Disorders, Post-Traumatic/epidemiology , Surveys and QuestionnairesABSTRACT
This study examined whether allelic status of the D2 dopamine receptor (DRD2) gene was associated with response to a selective serotonin reuptake inhibitor, paroxetine, in the treatment of posttraumatic stress disorder (PTSD). Sixty-three Caucasian war veterans with combat-related PTSD were treated with paroxetine for 8 weeks. Patients were assessed at baseline and at follow-up using the General Health Questionnaire-28 (GHQ). TaqI A DRD2 alleles were determined by PCR. Before paroxetine treatment, patients with the DRD2 A1+ allele (A1A2 genotype) compared to those with the A1- allele (A2A2 genotype) had higher total GHQ psychopathological scores (P=0.040) and higher GHQ subscale scores for anxiety/insomnia (0.046), social dysfunction (P=0.033) and depression (P=0.011). In an intention-to-treat analysis, paroxetine was associated with significant improvement in total GHQ scores (P=0.014) and in the factor scores of social dysfunction (P=0.033), anxiety (P=0.009) and depression (P=0.026). Furthermore, there was a significant allele by time interaction on the social dysfunction scale, with A1+ allelic patients showing significant improvement in social functioning compared to A1- allelic patients (P=0.031), an effect independent of changes in depression or anxiety. This suggests changes in social functioning induced by paroxetine may be, in part, mediated via D2 dopamine receptors. The DRD2 A1 allele may prove to be a useful marker to assist clinicians in predicting which patients with PTSD are likely to obtain improvements in social functioning with paroxetine treatment.
