ISSN 1671-3710
CN 11-4766/R

Advances in Psychological Science ›› 2022, Vol. 30 ›› Issue (1): 98-114.doi: 10.3724/SP.J.1042.2022.00098

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The mechanisms of histone modification in post-traumatic stress disorder

ZHANG Yingqian, ZHAO Guangyi, HAN Yuwei, ZHANG Jingyi, CAO Chengqi, WANG Li, ZHANG Kunlin()   

  1. CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
    Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2020-11-17 Online:2022-01-15 Published:2021-11-25


Post-traumatic stress disorder (PTSD) is a mental disorder with complex etiologies that usually occurs after people are exposed to traumatic events. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the criteria for PTSD included symptoms of intrusion, avoidance, negative alterations in cognitions and mood, and alterations in arousal and reactivity. The World Mental Health Surveys on Trauma and PTSD showed that more than 70% of individuals would experience traumatic events at least once in lifetime, while only a few would develop PTSD, suggesting individual differences in the genesis and development of PTSD.
Previous studies have proved that both genetic and environmental factors could influence the risk of PTSD, thus epigenetics, as a discipline investigating the interaction between environment and genes, has attracted the attention of researchers. Among the epigenetic mechanisms, histone modification has received widespread attention and has been researched in depth. Modification of histones by adding one or more chemical groups (such as acetyl group, methyl group, etc.) can lead to changes in chromatin structure and gene transcriptional activity, consequently regulating the level of gene expression. In recent years, histone modification has been implicated as an essential part in the pathogenesis of PTSD for the following reason: the development of PTSD is usually related to the maladaptation of fear memory induced by traumatic events, and histone modification plays an important role in the consolidation and extinction of fear memory correspondingly.
At present, techniques commonly used for the measurement of histone modification are Western Blotting and chromatin immunoprecipitation (ChIP), both based on the antibody technology. By combining ChIP with quantitative PCR (qPCR) technology, DNA microarray (also known as gene chip) technology or deep sequencing (Seq) technology, researchers can study the relationship between various types of histone modification and gene expression. What’s more, animal models are the main methods to explore the association between histone modification and PTSD, using electric shocks (e.g., inescapable foot shock, tail shock, and tone shock), social stress (e.g., predator exposure), and single prolonged stress (SPS) to simulate symptoms of PTSD in the laboratory.
We systematically searched and screened the literatures of histone modification in PTSD through PubMed (, PsychINFO (, and PsychArticles (, with finally 16 literatures selected for detailed integration and discussion. In spite of the nonnegligible heterogeneity among these studies, they proved the overall effect of histone modification was closely associated with the development of PTSD. Histone modification that enriched in the promoter regions of candidate genes like the Bdnf and Cdk5, could significantly increase the risk of PTSD. Alterations in levels of histone acetylation and methylation in hippocampus, amygdala, and prefrontal cortex are associated with PTSD, playing key roles in the consolidation, reconsolidation, and extinction of fear memory in PTSD-like animals. It is worth noting that histone modification is mainly involved in the regulation of the immune system, the serotonergic system, the neuropeptide Y-ergic system, and the NMDA receptor-related pathways. In addition, histone modification can be regulated by a variety of enzymes, leading to flexible regulation of PTSD, making drugs that target histone modification good choices for clinical treatment of PTSD.
Studying the neurobiological mechanisms of PTSD in human patients has been blocked by many factors; moreover, applying the results of animal models of PTSD to clinical research is a long way off. Therefore, using animal models to investigate the role of histone modification in the etiology of PTSD will remain a mainstream approach for some time to come.

Key words: post-traumatic stress disorder, histone modification, rodent model of PTSD, drug development

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