Psychoneuroimmunology and Trauma

Psychoneuroimmunology, Trauma, and PTSD

There are at least several clinical reasons to expect alterations in immune and endocrine system functions in PTSD cases. Investigations have shown that individuals who have developed PTSD following exposure to psychological trauma appear to have lower plasma cortisol concurrent with higher catecholamine levels. In addition, although studies have documented alterations in immune functioning following acute stress exposures, research has indicated that Vietnam veterans with PTSD have clinically elevated leukocyte and T cell counts. In addition, studies of nonveterans confirm that, although PTSD victims had reduced natural killer cell cytotoxicity, they also had significantly increased leukocyte counts. Thus, evidence indicates that exposure to severe environmental stressors and subsequent development of PTSD is related to altered neuroendocrine and immune system functions and that these alterations are related to the onset of immunoendocrine-related diseases. In particular, given the reduced cortisol levels often found among PTSD victims, it has been suggested that a downregulated glucocorticoid system results in elevations in leukocyte and other immune inflammatory activities. The hypothalamic-pituitary-adrenal (HPA) stress axis, and the adrenal gland in particular, is a major site for both the synthesis and interaction of numerous cytokines. For example, in addition to the cytokine-mediated activation of adrenal regulation, there are cytokine independent cell-mediated immune-adrenal interactions, and this immune-endocrine cross talk often is implicated in adrenal dysfunction and disease. Although complex physiologic processes appear to be involved with this pathogenic process, one pathway often cited involves the HPA stress axis concurrent with sympathetic-adrenomedullary (SAM) stress axis activation. These systems are significantly affected by glucocorticoids.

Glucocorticoids contribute to the maintenance of basal and stress-related homeostasis in all higher organisms. These hormones influence a large percentage of the expressed human genome, and they affect almost all organs and tissues. Glucocorticoids influence many functions of the central nervous system, including arousal, cognition, mood, and sleep, as well as cardiovascular tone, and immune and inflammatory responses. Research suggests that glucocorticoids are heavily involved in human pathophysiology. Common psychiatric and/or somatic disorders, such as anxiety, depression, insomnia, chronic pain and fatigue syndromes, obesity, metabolic syndrome, hypertension, type 2 diabetes, atherosclerosis, and osteoporosis—as well as autoimmune-inflammatory disorders, all appear to have a major glucocorticoid component. Glucocorticoids are among the most pervasive hormones in mammals. These steroid molecules reach all tissues, including the brain, readily penetrate cell membranes, and interact with cytoplasmic and nuclear glucocorticoid receptors, through which they exert their action. About 20% of the expressed human leukocyte genome is affected by glucocorticoids.

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