Neurophysiology and Psychopathology Underlying PTSD and Recent Insights into the PTSD Therapies-A Comprehensive Review

Abstract

Post-traumatic stress disorder (PTSD) is a well-known psychiatric disorder that affects millions of people worldwide. Pharmacodynamic and cognitive-behavioral therapies (CBT) have been used to treat patients with PTSD. However, it remains unclear whether there are concurrent changes in psychopathological and neurophysiological factors associated with PTSD patients. Past reports described those PTSD patients with efficient fatty acid metabolism, neurogenesis, mitochondrial energy balance could improve ability to cope against the conditioned fear responses and traumatic memories. Furthermore, cognitive, behavioral, cellular, and molecular evidence can be combined to create personalized therapies for PTSD sufferers either with or without comorbidities such as depression or memory impairment. Unfortunately, there is still evidence lacking to establish a full understanding of the underlying neurophysiological and psychopathological aspects associated with PTSD. This review has extensively discussed the single nucleotide polymorphism (SNPs) of genetic factors to cause PTSD, the implications of inflammation, neurotransmitter genomics, metabolic alterations, neuroendocrine disturbance (hypothalamus-pituitary-adrenal (HPA) axis), mitochondrial dynamics, neurogenesis, and premature aging related to PTSD-induced psychopathology and neurophysiology. In addition, the review delineated the importance of CBT and several pharmacodynamic therapies to mitigate symptomatology of PTSD.

Keywords: PTSD-treatment; SSRIs; neuroendocrine; neurogenesis; neuroinflammation; neurotransmitters.

Figure 1

Systemic changes correlated to psychopathological changes during post-traumatic stress disorder (PTSD): PTSD may be associated with multifactorial disorders in the human body. A dysregulation of the immune system fosters neurophysiological and psychopathological changes due to elevated pro-inflammatory mediators such as IL-6 and IL-17. Impaired balance in the catecholamine neurotransmitter levels (e.g., monoaminergic neurotransmitters) across the synaptic junction confers psychopathological changes in PTSD. Metabolic alterations and mitochondrial dysfunction in neurons foster the psychopathological andneurophysiological changes during PTSD. Balanced release of secretions through hypothalamus-pituitary-adrenal (HPA)-axis signaling is crucial for ameliorating the PTSD effects since HPA-axis dysregulation causes inflammation, insulin resistance, oxidative stress, and energy deficiency due to the increased levels of catecholamines and corticothropin release factor.