National Center for PTSD, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States.
National Center for PTSD, VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States.
J Affect Disord. 2019 Dec 1;259:201-209. doi: 10.1016/j.jad.2019.08.055. Epub 2019 Aug 19.
Evidence 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, the PPM1F gene, which has also been implicated in mechanisms of stress responding and is differentially expressed in individuals with comorbid PTSD and depression compared to controls.
Drawing from a sample of 240 white non-Hispanic trauma-exposed veterans, we tested 18 SNPs spanning the PPM1F gene for association with PTSD and cortical thickness.
Analyses revealed six PPM1F SNPs 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 corrected p'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-corrected p < 0.02).
Limitations of this study include the small sample size and that the sample was all-white, non-Hispanic predominately male veterans.
These results extend prior work linking PPM1F to PTSD and suggest that variants in this gene may have bearing on the neural integrity of the prefrontal cortex (PFC).
有证据表明，参与血清素信号和应激反应途径的基因中的单核苷酸多态性（SNPs）调节 PTSD 与皮质厚度之间的关联。本研究检查了这些途径的一个基因调节剂，即 PPM1F 基因，该基因也与应激反应机制有关，并且与 PTSD 和抑郁共病的个体与对照组相比，表达存在差异。
本研究从 240 名白种非西班牙裔创伤暴露的退伍军人样本中，测试了横跨 PPM1F 基因的 18 个 SNP 与 PTSD 和皮质厚度的关联。
分析显示，有 6 个 PPM1F SNP 调节了 PTSD 症状严重程度与双侧额上回和眶额回以及右侧三角部皮质厚度之间的关联（所有校正后的 p 值均<0.05），即 PTSD 严重程度越高，与基因型相关的皮质厚度越低。使用最相关的 SNP（rs9610608）进行的全皮质顶点分析显示，这种效应定位于右侧额上回的一个簇（簇校正后 p<0.02）。
本研究的局限性包括样本量小，以及样本全部为白人，非西班牙裔，主要为男性退伍军人。
这些结果扩展了先前将 PPM1F 与 PTSD 联系起来的工作，并表明该基因中的变体可能对前额叶皮质（PFC）的神经完整性有影响。
