Review demonstrates cellular stress and neuroinflammation drive circuit dysfunction in post-traumatic stress disorder, highlighting novel biomarker and therapeutic targets.
Key Points
To synthesize emerging evidence regarding how endoplasmic reticulum stress, inflammasome signaling, and neurotransmitter dysregulation drive the persistent neurobiological alterations of post-traumatic stress disorder (PTSD).
Narrative synthesis of molecular, neuroimmune, neuroimaging, and biomarker literature assessing chronic stress cascades in limbic and prefrontal brain circuits.
Evaluation of mechanistic interactions between endoplasmic reticulum stress pathways, inflammasome maturation, neurotransmitter imbalances, and structural brain alterations.
Activation of endoplasmic reticulum stress transducers (IRE1, ATF6) and the NLRP3 inflammasome stimulates caspase-1 and proinflammatory cytokines (IL-1β, IL-18), causing sustained microglial activation and impaired synaptic plasticity.
Cellular stress cascades are accompanied by disrupted glutamatergic and GABAergic neurotransmission, hypothalamic-pituitary-adrenal axis dysregulation, and volumetric reductions within the hippocampus, amygdala, and prefrontal cortex.