Carvalho Carolina Muniz, Coimbra Bruno Messina, Bugiga Amanda, Marques Diogo Ferri, Kiyomi Ota Vanessa, Mello Andrea Feijó, Mello Marcelo Feijó, Belangero Sintia Iole
Department of Psychiatry of Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
LiNC - Laboratory of Integrative Neuroscience of Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Complex Psychiatry. 2023 Feb 15;9(1-4):44-56. doi: 10.1159/000529698. eCollection 2023 Jan-Dec.
Sexual assault and a history of childhood sexual abuse (CSA) are related to posttraumatic stress disorder (PTSD) development. Long interspersed nuclear elements (LINE-1) are transposable elements, and their methylation is used to infer DNA global methylation. DNA methylation can be affected by trauma exposition which in turn would be associated with PTSD. Thus, we investigated if the LINE-1 methylation pattern is related to PTSD symptoms in females with a history of CSA.
This is a case-control study that examined, at baseline (W1), 64 women victims of sexual assault diagnosed with PTSD and 31 patients with PTSD who completed the 1-year follow-up (W2). Participants were categorized into two groups according to the presence of CSA (PTSDCSA+: NW1 = 19, NW2 = 10; PTSDCSA-: NW1 = 45, NW2 = 21). PTSD symptoms (re-experiencing, avoidance, hyperarousal, alterations in cognition/mood) were assessed using the Clinician-Administered PTSD Scale, and the history of CSA was assessed by the Childhood Trauma Questionnaire. LINE-1 methylation was measured in three sites (CpG1, CpG2, CpG3) located in the 5'UTR region using bisulfite conversion followed by pyrosequencing. Linear regression models were performed to test the relation between LINE-1 CpG sites methylation and PTSD symptoms.
We found a negative association between CpG2 methylation and hyperarousal symptoms among those in the PTSDCSA+ group in W1 (adjusted = 0.003) compared to the PTSDCSA- group ( > 0.05). Still, no association was observed between other PTSD symptoms and other CpG sites. Further, in the longitudinal analysis, LINE-1 hypomethylation was no longer observed in PTSD participants exposed to CSA.
Our findings suggest that LINE-1 methylation may help understand the relationship between trauma and PTSD. However, more studies are needed to investigate LINE-1 as an epigenetic marker of psychiatric disorders.
性侵犯和童年期性虐待(CSA)史与创伤后应激障碍(PTSD)的发生有关。长散在核元件(LINE-1)是可移动元件,其甲基化用于推断DNA整体甲基化。DNA甲基化会受到创伤暴露的影响,而创伤暴露又与PTSD相关。因此,我们研究了LINE-1甲基化模式是否与有CSA史的女性的PTSD症状有关。
这是一项病例对照研究,在基线时(W1)检查了64名被诊断为PTSD的性侵犯女性受害者和31名完成了1年随访的PTSD患者(W2)。参与者根据是否存在CSA分为两组(PTSDCSA+:W1时n = 19,W2时n = 10;PTSDCSA-:W1时n = 45,W2时n = 21)。使用临床医生管理的PTSD量表评估PTSD症状(重新体验、回避、过度警觉、认知/情绪改变),并通过儿童创伤问卷评估CSA史。使用亚硫酸氢盐转化后焦磷酸测序法在位于5'UTR区域的三个位点(CpG1、CpG2、CpG3)测量LINE-1甲基化。进行线性回归模型以测试LINE-1 CpG位点甲基化与PTSD症状之间的关系。
我们发现,与PTSDCSA-组相比,PTSDCSA+组中W1时CpG2甲基化与过度警觉症状之间存在负相关(校正β = 0.003),而PTSDCSA-组则无此相关(P>0.05)。此外,未观察到其他PTSD症状与其他CpG位点之间存在关联。此外,在纵向分析中,暴露于CSA的PTSD参与者中不再观察到LINE-1低甲基化。
我们的研究结果表明,LINE-1甲基化可能有助于理解创伤与PTSD之间的关系。然而,需要更多的研究来调查LINE-1作为精神疾病的表观遗传标记。