Mechanisms of Developing Post-Traumatic Stress Disorder: New Targets for Drug Development and Other Potential Interventions

Abstract

The post-traumatic stress disorder (PTSD) is defined as a severe anxiety disorder that develops after exposure to an event with actual, threatened, or perceived death or serious injury, or a threat to the physical integrity of oneself or others that results in significant psychological trauma. Moreover, the ability of people to handle acute severe stress experiences varies among individuals. Depending on the underlying personality and resiliency, therefore, PTSD can occur in individuals exposed to exceedingly stressful incidences or those who have encountered seemingly less overwhelming stressors. In addition to severe stressful exposure, multiple other factors including genetic susceptibility; past experiences; cultural, spiritual, and personal beliefs; bullying and harassments; and lack of support at the workplace, social, and home environement may contribute to the development of PTSD. Author investigated multiple potential mechanisms for the development and sustenance of PTSD based on the recent literature and his own experiences and insight. Based on this search, author indicates that among other pathological and biochemical abnormalities, hormonal aberrations are most likely key mechanisms initiating and the maintenance of the PTSD. These pathophysiological neuro-hormonal changes instigate maladaptive learning processes caused by sustained high levels of anxiety and fear, through a hypo-responsive hypothalamic-pituitary axis and hyper-responsive catecholamine system (persistently elevated blood norepinephrine levels and lower than appropriate glucocorticoid levels). In addition to having inappropriately low serum cortisol levels and high epinephrine and norepinephrine levels, patients with PTSD also have mitochondrial dysfunctions and other hormonal abnormalities. Based on these data, author concluded that these pathological, biochemical and sustained neurohormonal abnormalities are likely to influence the structural brain changes, particularly in the amygdala and hippocampus, which are characteristics of patients with PTSD. Considering these abnormalities, neuroendocrine system needs to be considered as a key target for new drug development for prevention and treatment of PTSD.

Endocrinological Mechanisms of Depressive Disorders and Ill Health

“…However, intense acute stress or frequent sustained stresses over a long period cause the negative biochemical and neurohormonal changes to become persistent, [2] these escalating stresses would lead to 'restructuring' of brain centers related to reasoning and behavior. [6] The adverse health issues of unmanaged stress and inappropriate or pathological responsiveness of the stress system affect and disrupt many bodily systems, including endocrine system; digestive system (stomachache, slow gastric emptying, enhanced colonic peristalsis leading to abdominal cramps and diarrhea); impairment of the immune system (frequent infections; chronic fatigue syndrome); changes in appetite and alteration of metabolism (weight gain or loss); cardiovascular dysfunction (hypertension, tachycardia, hyperlipidemia and hyperglycemia); nervous system manifestations (anxiety, depression, insomnia, lack of interest); and impaired memory. [6][7][8] Neurohormonal responses to stress…”

“…Persistent neurohormonal, biochemical and physiological abnormalities cause undesirable structural brain changes and several adverse health outcomes. [5,6] Consequences of the inability to cope with stress Feeling anxious, nervous, distracted and pressured are common when experiencing stress, but these feelings usually are transient. Additional signs and symptoms of stress include depression, fatigue, irritability, withdrawal, antisocial behavior, chest pain, dizziness, breathlessness, menstrual irregularities, erectile dysfunction and loss of libido.…”

“…Additional signs and symptoms of stress include depression, fatigue, irritability, withdrawal, antisocial behavior, chest pain, dizziness, breathlessness, menstrual irregularities, erectile dysfunction and loss of libido. [6] Although the majority of these are nonspecific, many including depression have an underlying etiology of disruption of endocrine system. [11,12] Physiological ways we cope with stress…”

“…[13,14] However, stresses that are severe may lead to pathological status with various clinical manifestations that requires psychological or medical assistance. [6] Regular, moderate exercises improve physical and psychological health and brain function, including memory. [5,6,15] The long-term effects of chronic stress can be reduced by minimizing oxidative stresses, such as eating a healthy diet and avoiding smoking and drinking too much alcohol.…”

“…[6] Regular, moderate exercises improve physical and psychological health and brain function, including memory. [5,6,15] The long-term effects of chronic stress can be reduced by minimizing oxidative stresses, such as eating a healthy diet and avoiding smoking and drinking too much alcohol. Most people need to be educated on how to cope with stresses rather than becoming dependent on prescription medications.…”