Post-traumatic stress disorder (PTSD) can become a chronic and severely disabling condition resulting in a reduced quality of life and increased economic burden. The disorder is directly related to exposure to a traumatic event, e.g., a real or threatened injury, death, or sexual assault. Extensive research has been done on the neurobiological alterations underlying the disorder and its related phenotypes, revealing brain circuit disruption, neurotransmitter dysregulation, and hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Psychotherapy remains the first-line treatment option for PTSD given its good efficacy, although pharmacotherapy can also be used as a stand-alone or in combination with psychotherapy. In order to reduce the prevalence and burden of the disorder, multilevel models of prevention have been developed to detect the disorder as early as possible and to reduce morbidity in those with established diseases. Despite the clinical grounds of diagnosis, attention is increasing to the discovery of reliable biomarkers that can predict susceptibility, aid diagnosis, or monitor treatment. Several potential biomarkers have been linked with pathophysiological changes related to PTSD, encouraging further research to identify actionable targets. This review highlights the current literature regarding the pathophysiology, disease development models, treatment modalities, and preventive models from a public health perspective, and discusses the current state of biomarker research.

Trauma exposure is one of the most important and prevalent risk factors for mental and physical ill-health. Prolonged or excessive stress exposure increases the risk of a wide variety of mental and physical symptoms, resulting in a condition known as post-traumatic stress disorder (PTSD). The diagnosis might be challenging due to the complex pathophysiology and co-existence with other mental disorders. The prime factor for PTSD development is exposure to a stressor, which variably, along with peritraumatic conditions, affects disease progression and severity. Additionally, many factors are thought to influence the response to the stressor, and hence reshape the natural history and course of the disease. With sufficient knowledge about the disease, preventive and intervenient methods can be implemented to improve the quality of life of the patients and to limit both the medical and economic burden of the disease. This literature review provides a highlight of up-to-date literature on traumatic stress, with a focus on causes or triggers of stress, factors that influence response to stress, disease burden, and the application of the social-ecological public health model of disease prevention. In addition, it addresses therapeutic aspects, ethnic differences in traumatic stress, and future perspectives, including potential biomarkers.

Exposure to trauma is one of the most important and prevalent risk factors for mental and physical ill-health. Excessive or prolonged stress exposure increases the risk of a wide variety of mental and physical symptoms. However, people differ strikingly in their susceptibility to develop signs and symptoms of mental illness after traumatic stress. Post-traumatic stress disorder (PTSD) is a debilitating disorder affecting approximately 8% of the world’s population during their lifetime, and typically develops after exposure to a traumatic event. Despite that exposure to potentially traumatizing events occurs in a large proportion of the general population, about 80–90% of trauma-exposed individuals do not develop PTSD, suggesting an inter-individual difference in vulnerability to PTSD. While the biological mechanisms underlying this differential susceptibility are unknown, epigenetic changes have been proposed to underlie the relationship between exposure to traumatic stress and the susceptibility to develop PTSD. Epigenetic mechanisms refer to environmentally sensitive modifications to DNA and RNA molecules that regulate gene transcription without altering the genetic sequence itself. In this review, we provide an overview of various molecular biological, biochemical and physiological alterations in PTSD, focusing on changes at the genomic and epigenomic level. Finally, we will discuss how current knowledge may aid us in early detection and improved management of PTSD patients.

Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS. We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls. Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop upon exposure to a traumatic event. While most people are able to recover promptly, others are at increased risk of developing PTSD. However, the exact underlying biological mechanisms of differential susceptibility are unknown. Identifying biomarkers of PTSD could assist in its diagnosis and facilitate treatment planning. Here, we identified serum microRNAs (miRNAs) of subjects that underwent a traumatic event and aimed to assess their potential to serve as diagnostic biomarkers of PTSD. Next-generation sequencing was performed to examine circulating miRNA profiles of 24 members belonging to the Dutch military cohort Prospective Research in Stress-Related Military Operations (PRISMO). Three groups were selected: “susceptible” subjects who developed PTSD after combat exposure, “resilient” subjects without PTSD, and nonexposed control subjects (N = 8 per group). Differential expression analysis revealed 22 differentially expressed miRNAs in PTSD subjects compared to controls and 1 in PTSD subjects compared to resilient individuals (after multiple testing correction and a log2 fold-change cutoff of ≥|1|). Weighted Gene Coexpression Network Analysis (WGCNA) identified a module of coexpressed miRNAs which could distinguish between the three groups. In addition, receiver operating characteristic curve analyses suggest that the miRNAs with the highest module memberships could have a strong diagnostic accuracy as reflected by high areas under the curves. Overall, the results of our pilot study suggest that serum miRNAs could potentially serve as diagnostic biomarkers of PTSD, both individually or grouped within a cluster of coexpressed miRNAs. Larger studies are now needed to validate and build upon these preliminary findings.