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.

Dysregulation of miR-15a-5p, miR-497a-5p and miR-511-5p Is Associated with Modulation of BDNF and FKBP5 in Brain Areas of PTSD-Related Susceptible and Resilient Mice

“…All these findings would suggest that these miRNAs are part of a complex transcriptional and post-transcriptional machinery that controls fundamental processes in neurons and, consequently, their dysregulation would contribute to molecular cascades induced by neuropsychological stress. Moreover, enrichment analysis of miR-15a-5p, miR-497a-5p, miR-511-5p, and let-7d-5p network showed that such miRNA circuits could affect multiple cellular and molecular processes associated with PTSD pathogenesis [ 47 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ]. Based on these considerations, the inverse correlation between arousal score and hippocampal expression of miR-15a-5p and miR-511-5p is not surprising, as it suggests the existence of a linear relationship between the behavioral arousal score of mice and miRNA levels in the brain that, in turn, coherently influences BDNF and FKBP5 transcripts.…”

Assessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction

“…One potential biomarker that could be useful in the assessment of individual stress is trimethylamine-N-oxide (TMAO). This gut bacteria-derived metabolite is an important cardiovascular risk marker that appears to interfere with many important physiological regulatory pathways (Aliev et al, 2020 ; Giannoni-Pastor, Eiroa-Orosa, Fidel Kinori, Arguello, & Casas, 2016 ).…”

The Association between Child and Parent Psychiatric Disorders in Families Exposed to Flood and/or Dioxin

“…In adults in particular, biological underpinnings of PTSD have been demonstrated, which involve the hypothalamus-pituitary-adrenal (HPA) axis, neural circuitry of the limbic system, especially the amygdala, the prefrontal cortex, and the hippocampus, and its connections to the parahippocampal gyrus, orbitofrontal cortex, sensorimotor cortex, thalamus, and anterior cingulate cortex. The neuropathological findings in PTSD reflect excessive activation of the amygdala coupled with an underactive medial prefrontal cortex coupled with insufficient inhibition of strong responses to threat of danger from the amygdala [ 70 , 71 , 72 , 73 ]. Biological correlates of child disaster outcomes have also been considered [ 74 ].…”