Defining the nuanced nature of redox biology in post-traumatic stress disorder

Abstract

Post-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of redox biology. Redox molecules are free radical and/or reactive species that are generated as a consequence of the necessity of electron movement for life. These reactive molecules, too, are essential for life, but in excess are denoted as “oxidative stress” and often associated with many diseases. The few studies that have examined redox biology parameters have often utilized outdated and nonspecific methods, as well as have reported confounding results, which has made it difficult to conclude the role for redox in PTSD. Herein, we provide a foundation of how redox biology may underlie diseases like PTSD, critically examine redox studies of PTSD, and provide future directions the field can implement to enhance standardization, reproducibility, and accuracy of redox assessments for the use of diagnosis, prognosis, and therapy of this debilitating mental health disorder.

Mitochondrial dysfunction as a possible trigger of neuroinflammation at post-traumatic stress disorder (PTSD)

“…NADH dehydrogenase is generally considered as the main site of ROS production in the mitochondria ( Zhao et al, 2019 ). Actually, the oxidative stress observed in PTSD may underlie its pathophysiology ( Lushchak et al, 2023 ; Reed and Case, 2023 ).…”

“…Development of oxidative stress is an integral feature of the pathophysiology of PTSD ( Lushchak et al, 2023 ; Reed and Case, 2023 ). Oxidative stress results from an imbalance between ROS formation and elimination leading to increased steady-state ROS levels and number of physiological consequences ( Lushchak, 2014 ).…”

“NO” Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD

“…Consequently, nitrosative stress can result in adverse effects including increased blood-brain barrier permeability, impaired neurogenesis and synaptic plasticity, alterations in neurotransmission, changes in neural morphology, and disruptions in overall cellular signaling [ 185 ]. These factors collectively contribute to the pathophysiology of PTSD, although clinical evidence remains contradictory considering the challenges of measuring nitrosative components and biological markers [ 187 , 188 ]. Interestingly, scavenging ROS with N-acetyl cysteine, a potent antioxidant, in LA before extinction training attenuates fear renewal [ 75 ].…”