Of Soldiers and Their Ghosts: Are We Ready for a Review of PTSD Evidence?

Abstract

Psychosocial trauma has accompanied mankind since time immemorial and has been sufficiently portrayed in art and literature to suggest that posttraumatic stress disorder may be as old as combat itself. Since war is more frequent in human history than peace, public health measures are confined to mitigating the detrimental impact of battlefield experiences on combat participants. At present, PTSD outcome studies show mixed results, marked by high nonresponse rates, therapy dropout, and completed suicide, suggesting that novel strategies are urgently needed. Those of us who work routinely with combat veterans have noted an increasing trend of patients preferring mindfulness-based therapies as opposed to trauma-centered treatments, such as prolonged exposure or trauma-focused cognitive behavioral therapy. Preference for mindfulness over trauma-based therapies appears to coincide with the shift in research focus from the amygdala and fear to the insular cortex and interoceptive awareness. Therefore, rethinking PTSD as insular pathology is driven by the recent findings that neurons in this cortical area not only regulate cardiac rhythm but also record past intestinal inflammations. These discoveries likely explain the high comorbidity of stress-related disorders with premature endothelial senescence and a dysfunctional intestinal barrier. Moreover, the identification of the cholinergic anti-inflammatory pathway and the revelation that endothelial cells express alpha-7 nicotinic receptors has brought PTSD prevention and early detection within reach. In this narrative review, we discuss the relationship between early vascular aging, gut barrier disruption, and PTSD. We also examine the link between this pathology and faulty interoceptive awareness, surmising that hypertension and decreased heart rate variability are PTSD risk factors, while lipopolysaccharide, lipopolysaccharide binding protein, soluble CD14, microbial cell-free DNA, acyloxyacyl hydrolase, and IL22 comprise early detection markers of this disorder.