Gen Li1,2, Li Wang1,2, Kunlin Zhang1,2, Chengqi Cao2,3, Xing Cao1,2, Ruojiao Fang1,2, Ping Liu4, Shu Luo4, Xiangyang Zhang1,2. 1. Laboratory for Traumatic Stress Studies, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. 2. Department of Psychology, University of Chinese Academy of Sciences, Beijing, China. 3. Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen University, Shenzhen, China. 4. People's Hospital of Deyang City, Deyang, Sichuan, China.
Abstract
BACKGROUND: Post-traumatic stress disorder (PTSD) and depression are common mental disorders in individuals experiencing traumatic events. To date, few studies have studied the relationship between genetic basis and phenotypic heterogeneity of traumatized individuals. The present study examined the effects of four FKBP5 SNPs (rs1360780, rs3800373, rs9296158, and rs9470080) in four postdisaster groups (low symptom, predominantly depressive, predominantly PTSD, and combined PTSD-depression symptom groups) as identified by latent profile analysis. METHODS: A total of 1,140 adults who experienced the 2008 Wenchuan earthquake participated in our study. Earthquake-related trauma, PTSD, and depressive symptoms were measured using standard psychometric instruments. The four FKBP5 SNPs were genotyped using a custom-by-design 2 × 48-Plex SNP scan™ Kit. RESULTS: After adjusting for covariates, the main and gene-environment interaction effects of rs9470080 were all significant when the combined PTSD-depression group was compared with the low symptoms, predominantly depression and predominantly PTSD groups. rs9470080 TT genotype carriers had a higher risk of developing high co-occurring PTSD and depression symptoms than the C allele carriers. However, when trauma exposure was severe, the TT genotype carriers and C allele carriers did not differ in the risk of developing high co-occurring PTSD and depressive symptoms. The other three SNPs demonstrated no significant effects. Moreover, the rs3800373-rs9296158-rs1360780-rs9470080 haplotype A-G-C-T was found significantly associated with combined PTSD-depression symptoms. CONCLUSION: Our findings support the genetic basis of phenotypic heterogeneity in people exposed to trauma. Furthermore, the results reveal the possibility that the variants of FKBP5 gene may be associated with depression-PTSD comorbidity.
BACKGROUND: Post-traumatic stress disorder (PTSD) and depression are common mental disorders in individuals experiencing traumatic events. To date, few studies have studied the relationship between genetic basis and phenotypic heterogeneity of traumatized individuals. The present study examined the effects of four FKBP5 SNPs (rs1360780, rs3800373, rs9296158, and rs9470080) in four postdisaster groups (low symptom, predominantly depressive, predominantly PTSD, and combined PTSD-depression symptom groups) as identified by latent profile analysis. METHODS: A total of 1,140 adults who experienced the 2008 Wenchuan earthquake participated in our study. Earthquake-related trauma, PTSD, and depressive symptoms were measured using standard psychometric instruments. The four FKBP5 SNPs were genotyped using a custom-by-design 2 × 48-Plex SNP scan™ Kit. RESULTS: After adjusting for covariates, the main and gene-environment interaction effects of rs9470080 were all significant when the combined PTSD-depression group was compared with the low symptoms, predominantly depression and predominantly PTSD groups. rs9470080 TT genotype carriers had a higher risk of developing high co-occurring PTSD and depression symptoms than the C allele carriers. However, when trauma exposure was severe, the TT genotype carriers and C allele carriers did not differ in the risk of developing high co-occurring PTSD and depressive symptoms. The other three SNPs demonstrated no significant effects. Moreover, the rs3800373-rs9296158-rs1360780-rs9470080 haplotype A-G-C-T was found significantly associated with combined PTSD-depression symptoms. CONCLUSION: Our findings support the genetic basis of phenotypic heterogeneity in people exposed to trauma. Furthermore, the results reveal the possibility that the variants of FKBP5 gene may be associated with depression-PTSD comorbidity.
Entities:
Keywords:
FKBP5; G × E study; PTSD; depression; phenotypic heterogeneity
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