Post-traumatic stress disorder (PTSD) is a severe psychiatric condition associated with persistent emotional dysregulation, cognitive impairment, and structural alterations in limbic and prefrontal brain regions. Growing evidence indicates that chronic inflammation and abnormal processing of pro-inflammatory cytokines are central components of PTSD pathophysiology. Activation of the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) and caspase-1 promotes the proteolytic maturation of pro-interleukin-1β (pro-IL-1β) and pro-interleukin-18 (pro-IL-18) into their active forms, amplifying neuroinflammatory signaling. Sustained microglial activation and disrupted neuron-microglia-astrocyte communication contribute to synaptic dysfunction and impaired neuroplasticity. In parallel, dysregulation of the hypothalamic-pituitary-adrenal axis (HPA axis) interacts with inflammatory pathways, leading to altered stress responses and persistent immune activation. Clinical studies have demonstrated associations between circulating inflammatory mediators, including IL-18 and IL-1β, and the severity of emotional inhibition, sleep disturbances, and maladaptive coping strategies in PTSD. Moreover, inflammatory activity has been linked to volumetric and microstructural changes in the hippocampus, amygdala, and prefrontal cortex observed in chronic PTSD. These findings support the concept that the processing of pro-inflammatory cytokines is a central mechanism in PTSD rather than a secondary consequence of stress exposure. Understanding the molecular pathways underlying cytokine maturation and neuroimmune signaling may contribute to improved biomarker-based diagnostics and the development of targeted therapeutic interventions.
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.
