Keywords
Abstract
Post-traumatic stress disorder (PTSD) is a complex somatic, cognitive, and behavioral condition characterized by the repetition of extremely traumatic experiences that can lead to significant occupational and interpersonal dysfunction as a result of traumatic events. Although PTSD is considered primarily a psychiatric condition, due to neurological and endocrine disturbances it is also characterized by a number of somatic comorbidities, including metabolic syndrome (MS). Analysis of prospective longitudinal studies of the relationship between PTSD symptoms and MS suggests that PTSD severity is proportional to further increase in MS severity. Therefore, the question arises about the main biological regulatory mechanisms that cause PTSD and MS, and can be taken into account when developing pharmacotherapeutic approaches for the treatment of PTSD and related metabolic dysfunctions.
The aim of the study is to analyze the data of the scientific literature regarding modern views on the mechanisms of dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which underlie the development of PTSD and are also involved in metabolic dysfunctions.
The frequency of comorbidity that occurs between MS and PTSD suggests the presence of internal neurological and endocrine changes, as well as changes in metabolism. This complex phenotype results from interactions between genetic, other biological and environmental factors. It has been hypothesized that PTSD develops under conditions of damage to the natural ability to adapt to stress. In contrast to acute stress in PTSD, there is a complex modulation of the main mediators of the HPA response to stress and anxiety, which are involved in the regulation of the central and autonomic nervous systems, including the strengthening of inhibitory feedback systems and inhibition of the HPA axis. As a result of modifying the sensitivity of receptors to neurotransmitters and/or the expression profile of key genes, there may be an imbalance in the levels of receptors responsible for the initiation of stress reactions or, conversely for the restoration of homeostasis.
Changes in some of the characteristic features of MS observed in people with PTSD highlight the similarities between these two disorders – both pathologies are affected by three metabolic mediators: cortisol, neuropeptide Y and oxytocin. However, there are some differences: cortisol and neuropeptide Y, while
contributing to diminish PTSD severity, simultaneously exacerbate obesity, and stress-mediated oxytocin release simultaneously reduces the severity of both conditions. So far, enough experimental data have been accumulated that showed antidepressant properties of antihyperglycemic agents on the one hand, as well as the positive effect of selective serotonin reuptake inhibitors on the control of blood glucose levels in patients with glucose metabolism disorders and the body weight in obese people.
The relevance of a polypharmacological strategy to increase the effectiveness of drugs in the treatment of comorbid mental and physical disorders is emphasized.