Neuroimmune mechanisms in PTSD: inflammatory heterogeneity, circuit dysfunction, and biomarker-based subtypes.

Authors

Shreyasi Majumdar, Puneet K Samaiya, Sahabuddin Ahmed, Sairam Krishnamurthy, Santosh Kumar Prajapati

Published in

Molecular biology reports. Volume 53. Issue 1. Jun 18, 2026. Epub Jun 18, 2026.

Abstract

Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear response, anxiety, hyperarousal and sleep disturbances. One of the major pathophysiological mechanisms underlying the development of PTSD is the dysregulation of the hypothalamic-pituitary-adrenal axis. However, the molecular and cellular mechanisms underlying the development of the disease remain poorly understood due to the heterogeneity of the clinical symptoms and disease course. There is emerging evidence that peripheral immune signaling, endocrine regulation, and glial-vascular interactions play a role in modulating neural circuit functions, which in turn can impact synaptic plasticity and network dynamics. In this review, we integrate evidence from cytokine and immune cell profiling, epigenetic and transcriptomic analyses, experimental immune activation studies. We elaborated neuroimaging, including the translocator protein-positron emission tomography (TSPO-PET) as a marker of glial activation state, to summarize the potential role of immune-brain interactions in modulating circuit and network phenotypes in PTSD. Recently, studies emphasized the role of inflammatory biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-α), as well as changes in monocyte and T-cell phenotypes, in PTSD. In this review, we focus on the neuroimmune interface in PTSD, including immune-activated and immune-altered phenotypes that may relate to different underlying dysfunctions in neural circuits. We also elaborated the interactions between immune signaling, endocrine control, and neural networks that may trigger clinical heterogeneity in PTSD. Notably, future studies that incorporate peripheral markers with multimodal neuroimaging will be critical for validating these underlying mechanisms.

PMID:
42313200
Bibliographic data and abstract were imported from PubMed on 18 Jun 2026.

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