19 research outputs found
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5-HT2A Gene Variants Moderate the Association between PTSD and Reduced Default Mode Network Connectivity
The default mode network (DMN) has been used to study disruptions of functional connectivity in a wide variety of psychiatric and neurological conditions, including posttraumatic stress disorder (PTSD). Studies indicate that the serotonin system exerts a modulatory influence on DMN connectivity; however, no prior study has examined associations between serotonin receptor gene variants and DMN connectivity in either clinical or healthy samples. We examined serotonin receptor single nucleotide polymorphisms (SNPs), PTSD, and their interactions for association with DMN connectivity in 134 White non-Hispanic veterans. We began by analyzing candidate SNPs identified in prior meta-analyses of relevant psychiatric traits and found that rs7997012 (an HTR2A SNP), implicated previously in anti-depressant medication response in the Sequenced Treatment Alternatives for Depression study (STAR*D; McMahon et al., 2006), interacted with PTSD to predict reduced connectivity between the posterior cingulate cortex (PCC) and the right medial prefrontal cortex and right middle temporal gyrus (MTG). rs130058 (HTR1B) was associated with connectivity between the PCC and right angular gyrus. We then expanded our analysis to 99 HTR1B and HTR2A SNPs and found two HTR2A SNPs (rs977003 and rs7322347) that significantly moderated the association between PTSD severity and the PCC-right MTG component of the DMN after correcting for multiple testing. Finally, to obtain a more precise localization of the most significant SNP × PTSD interaction, we performed a whole cortex vertex-wise analysis of the rs977003 effect. This analysis revealed the locus of the pre-frontal effect to be in portions of the superior frontal gyrus, while the temporal lobe effect was centered in the middle and inferior temporal gyri. These findings point to the influence of HTR2A variants on DMN connectivity and advance knowledge of the role of 5-HT2A receptors in the neurobiology of PTSD
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SKA2 Methylation is associated with Decreased Prefrontal Cortical Thickness and Greater PTSD Severity among Trauma-Exposed Veterans
Methylation of the SKA2 gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness, and psychiatric phenotypes linked to suicide in trauma-exposed veterans. 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the CpG locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated SNP (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD), and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylationadj). Specifically, DNA methylationadj was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylationadj and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylationadj of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility