A review on inflammatory cytokine-induced alterations of the brain as potential neural biomarkers in post-traumatic stress disorder.

The heterogeneity of post-traumatic stress disorder (PTSD) symptoms indicates that multiple neurobiological mechanisms underlie the pathophysiology of the condition. However, no generally accepted PTSD biomarkers in clinical practice currently exist. The sequential responses to recurrent and chronic stress by the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) system are considered to play a significant role in the onset and progression of PTSD. Decreased activity of the HPA axis and parasympathetic nervous system, along with increased activity of the sympathetic nervous system, have been observed in PTSD, which may lead to increased levels of proinflammatory cytokines. Such heightened activity of the immune system may cause alterations in the structure and function of brain regions-for example, the amygdala, hippocampus, medial prefrontal cortex, anterior cingulate cortex, and insula-through changes in levels of serotonin and kynurenine pathway metabolites, and direct neurotoxic effects of cytokines. Although chronic inflammation-induced alterations in brain regions critical in controlling emotional behavior and fear regulation may represent a strong candidate biomarker of PTSD, future studies are necessary to further elucidate inflammation-associated neural biomarkers of PTSD. Continued research on therapeutic methods that involve the normalization of the HPA axis, ANS, and immune system is expected to contribute to the development of novel ways to treat PTSD.