The PPM1F gene moderates the association between PTSD and cortical thickness.
The PPM1F gene moderates the association between PTSD and cortical thickness.
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DOI：
10.1016/j.jad.2019.08.055
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发表时间：
2019-12
影响因子：
6.6
通讯作者：
Danielle R. Sullivan;Filomene G. Morrison;E. Wolf;M. Logue;C. Fortier;D. Salat;J. Fonda;Annjanette Stone;S. Schichman;W. Milberg;R. McGlinchey;Mark W. Miller
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文献类型：
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作者：
Danielle R. Sullivan;Filomene G. Morrison;E. Wolf;M. Logue;C. Fortier;D. Salat;J. Fonda;Annjanette Stone;S. Schichman;W. Milberg;R. McGlinchey;Mark W. Miller
研究背景有证据表明，参与神经递质信号传导和应激反应途径的基因的单核苷酸多态性（single nucleotide polymorphisms，SNPs）调节了创伤后应激障碍与皮质厚度之间的关系。本研究检查了这些途径的遗传调节因子，PPM1F基因，该基因也与应激反应机制有关，并且与controls.MethodsDrawing的240名白色非西班牙裔创伤暴露退伍军人的样本相比，在患有PTSD和抑郁症的个体中差异表达。我们检测了18个PPM1F基因的SNPs与PTSD和皮质厚度的相关性。结果分析显示，6个PPM1FSNPs调节了PTSD症状严重程度和皮质厚度之间的相关性。双侧上级额叶和眶额区以及右侧三角部的皮质厚度（所有校正值均< 0.05），因此，更大的PTSD严重程度与作为基因型函数的皮质厚度减少有关。使用最相关SNP的全皮层顶点分析（rs9610608）显示这种效应局限于右侧额上级回的一簇（聚类校正p < 0.02）。局限性本研究的局限性包括样本量小，样本都是白人，非结论这些结果扩展了先前将PPM1F与PTSD联系起来的工作，并表明该基因的变异可能与神经系统疾病有关。前额叶皮层（PFC）的完整性。
BackgroundEvidence suggests that single nucleotide polymorphisms (SNPs) in genes involved in serotonergic signaling and stress response pathways moderate associations between PTSD and cortical thickness. This study examined a genetic regulator of these pathways, thePPM1Fgene, which has also been implicated in mechanisms of stress responding and is differentially expressed in individuals with comorbid PTSD and depression compared to controls.MethodsDrawing from a sample of 240 white non-Hispanic trauma-exposed veterans, we tested 18 SNPs spanning thePPM1Fgene for association with PTSD and cortical thickness.ResultsAnalyses revealed sixPPM1FSNPs that moderated associations between PTSD symptom severity and cortical thickness of bilateral superior frontal and orbitofrontal regions as well as the right pars triangularis (all correctedp’s < 0.05) such that greater PTSD severity was related to reduced cortical thickness as a function of genotype. A whole-cortex vertex-wise analysis using the most associated SNP (rs9610608) revealed this effect to be localized to a cluster in the right superior frontal gyrus (cluster-correctedp< 0.02).LimitationsLimitations of this study include the small sample size and that the sample was all-white, non-Hispanic predominately male veterans.ConclusionsThese results extend prior work linkingPPM1Fto PTSD and suggest that variants in this gene may have bearing on the neural integrity of the prefrontal cortex (PFC).