Posttraumatic Stress Disorder (PTSD): Biochemical Network and Methodologies

PTSD is a syndrome with multiple faces due to its pathophysiology complexity. Signals of the illness may include physiological alterations in the organism, tissues, cells, proteins, and gene levels. Therefore, PTSD has been understood as a systemic disease that affects not only the brain but also the whole body. Heterogeneity in susceptibility to PTSD suggests that the response of an individual to trauma may depend on gender as well as the type of adverse event experienced. In addition, people who meet PTSD diagnostic criteria are heterogeneous, as demonstrated by differences in treatment response, course, and symptoms. According to evidence, there is a need to elucidate the biochemical mechanisms involved in PTSD especially looking for the identification of specific biomarkers for the disease. PTSD biomarkers could be used to improve the disease's diagnosis, early identification of cases, treatment decision-making, and new drug development. Here we review the recent literature available in Pubmed investigating the main biochemical mechanisms involved in PTSD and the methodologies applied for the assessment of the disease. In addition to trauma-induced alterations, PTSD presents pre-exposure vulnerability factors. The disease has been found to be associated with the hypothalamus-pituitary-thyroid (HPT) axis and hypothalamic-pituitary-adrenal axis (HPA) dysfunctions. Changes in the activity of the sympathetic nervous system (SNS) play a role in PTSD by releasing epinephrine and norepinephrine. The release of cortisol from the adrenal cortex amplifies the SNS response. Later through negative feedback mechanisms, the cortisol level is decreased in patients with PTSD, especially in women. The women's increased vulnerability to PTSD may be due to gender differences in normal HPA reactivity. That negative feedback contributes to neuroendocrine alterations, promoting structural brain changes that finally culminate in PTSD. Abnormal levels of serotonin and dopamine have been found in the disease. Mechanisms like the alterations in mitochondrial energy handling and induction of neuroinflammation are also associated with PTSD.