Neuromolecular biomarkers of traumatic stress: Refining diagnostic criteria and personalizing treatment for core biological symptoms in PTSD.

Abstract

Objective: Aim: The aim of this review is to assess the role of neuromolecular biomarkers in post-traumatic stress disorder (PTSD) and their usefulness in improving diagnostic accuracy and supporting personalized treatment strategies.

Patients and methods: Materials and Methods: A narrative review of studies published between 2015 and 2025 was performed using databases such as PubMed, Scopus, and Web of Science. The analysis included clinical and experimental studies focusing on neuroinflammation, oxidative stress, endoplasmic reticulum stress, and markers of neuronal damage in PTSD. Special attention was given to associations between biomarkers and symptom severity, duration of illness, and treatment outcomes.

Results: Results: PTSD is associated with disturbances in neuroimmune and neuroendocrine pathways. Increased levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18), are frequently observed. Activation of the NLR family pyrin domain containing 3 inflammasome (NLRP3 inflammasome) and elevated oxidative stress markers, such as malondialdehyde (MDA), indicate ongoing inflammatory and oxidative processes. Changes in neuronal injury markers, including ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), suggest neurodegenerative mechanisms. Altered chemokine signaling, particularly fractalkine (chemokine C-X3-C motif ligand 1, CX3CL1), and activation of endoplasmic reticulum stress pathways, such as inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6), are linked to impaired neuronal function and reduced synaptic plasticity. These findings indicate biological heterogeneity within PTSD.

Conclusion: Conclusions: Neuromolecular biomarkers may improve the current symptom-based diagnostic model of PTSD. Their integration with clinical assessment tools may support identification of biologically defined subgroups and enable more targeted treatment.