Abstract
Post-traumatic stress disorder (PTSD), Major Depressive Disorder (MDD), and Substance Use Disorder (SUD) have large public health impacts. Therefore, researchers have attempted to identify those at greatest risk for these phenotypes. PTSD, MDD, and SUD are in part genetically influenced. Additionally, genes in the glutamate and gamma-aminobutyric acid (GABA) system are implicated in the encoding of emotional and fear memories, and thus may impact these phenotypes. The current study examined the associations of single nucleotide polymorphisms in GAT1 individually, and at the gene level, using a principal components (PC) approach, with PTSD, PTSD comorbid with MDD, and PTSD comorbid with SUD in 486 combat-exposed veterans. Findings indicate that several GAT1 SNPs, as well as one of the GAT1 PCs, was associated with PTSD, with and without MDD and SUD comorbidity. The present study findings provide initial insights into one pathway by which shared genetic risk influences PTSD-MDD and PTSD-SUD comorbidities, and thus identify a high-risk group (based on genotype) on whom prevention and intervention efforts should be focused.
Highlights
There exists a notable, and important, disconnect between rates of traumatic event exposure and development of negative outcomes such as post-traumatic stress disorder (PTSD)
Out of the 314 Post-traumatic stress disorder (PTSD) cases, 203 (64.6%) cases were diagnosed with Major Depressive Disorder (MDD), 99 (31.5%) cases had a history of Substance Use Disorder (SUD), and 78 (24.8%) cases had PTSD without MDD or SUD, whereas only six out of the 172 controls (3.5%) had MDD or SUD
Among the four principal components we considered, PC1 was significantly associated with PTSD (OR = 0.84, 95% CI: 0.73–0.96, p = 0.012) among Caucasians, after adjusting for age, sex, and Combat Exposure Scale (CES)
Summary
There exists a notable, and important, disconnect between rates of traumatic event exposure and development of negative outcomes such as post-traumatic stress disorder (PTSD). Genes examined from biological candidate systems in relation to PTSD have included polymorphisms of genes from the dopaminergic system (e.g., DAT1, DRD2 [4]), the promoter region of the serotonin transporter system (5-HTTLPR [5]), and the hypothalamic pituitary adrenal axis (i.e., stress-response) system (e.g., glucocorticoid receptor [6]), among others.
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