Document Type : Review Article
Authors
- Amir Hossein Rajabi 1
- Samaneh Zafarabadi 2
- Kimia Jazi 3
- Maryam Moghbel Baerz 4
- Omid Bahrami 5
- Gelareh Azarinoush 3
- Pardis Habibi 6
- Negar Azami 7
- Shahram Paydar 8
1 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
2 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
3 Research and Development Center, Shahid Beheshti Hospital, Qom University of Medical Sciences, Qom, Iran
4 1. Brain Mapping Research Center, Research Institute of Functional Neurosurgery, Shahid Beheshti University of Medical Sciences 2. Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
5 School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
6 1. Research Center for Psychiatry and Behavioral Sciences, Shiraz University of Medical Sciences, Shiraz, Iran 2. Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
7 Universal Scientific Education and Research Network, Tehran, Iran
8 Trauma Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
Background: Post-traumatic stress disorder (PTSD) is prevalent among combat veterans, influenced by genetic, epigenetic, and environmental factors. Immune dysregulation and systemic inflammation play critical roles in its pathophysiology. This systematic review explores gene expression and DNA methylation patterns to identify key pathways and targets involved in its war-related subtype.
Objectives: To analyze genetic and methylation modifications associated with PTSD among war veterans, emphasizing actionable therapeutic targets and biomarkers.
Search Strategy: A comprehensive search of PubMed, Scopus, and Web of Science was conducted using specific keywords related to PTSD, gene expression, and DNA methylation, restricted to studies published between 2000 to 2024.
Selection Criteria: Studies involving adult military personnel with confirmed PTSD based on DSM-5 criteria were included. Animal studies, psychological interventions, and pharmacological research were excluded. Only cross-sectional, case-control, or cohort studies using blood, saliva, or brain tissue samples were considered.
Data Collection and Analysis: Data from 28 studies were extracted using a predefined framework, focusing on population characteristics, study design, and identified hub genes.
Main Results: Key findings revealed upregulation of immune-related genes (e.g., CCL4, NF-κB) and hypomethylation of inflammation-related genes. Downregulation of neurodevelopmental genes, such as BDNF and DSCAM, highlighted disruptions in synaptic plasticity. Identified pathways suggest potential biomarkers and therapeutic targets for precision medicine approaches.
Conclusions: This review highlights the role of alterations in gene expression in war-related PTSD. The identified genes can be candidates for personalized therapies. Further research is needed to validate these findings and develop targeted interventions.
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