scholarly journals Loss of Prefrontal Cortical Higher Cognition with Uncontrollable Stress: Molecular Mechanisms, Changes with Age, and Relevance to Treatment

2019 ◽  
Vol 9 (5) ◽  
pp. 113 ◽  
Author(s):  
Dibyadeep Datta ◽  
Amy Arnsten
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Pharmacological Treatments ◽  
Post Traumatic Stress ◽  
Uncontrollable Stress ◽  
Prefrontal Cortical ◽  
Post Traumatic ◽  
Cell Firing ◽  
Increased Susceptibility

The newly evolved prefrontal cortex (PFC) generates goals for “top-down” control of behavior, thought, and emotion. However, these circuits are especially vulnerable to uncontrollable stress, with powerful, intracellular mechanisms that rapidly take the PFC “off-line.” High levels of norepinephrine and dopamine released during stress engage α1-AR and D1R, which activate feedforward calcium-cAMP signaling pathways that open nearby potassium channels to weaken connectivity and reduce PFC cell firing. Sustained weakening with chronic stress leads to atrophy of dendrites and spines. Understanding these signaling events helps to explain the increased susceptibility of the PFC to stress pathology during adolescence, when dopamine expression is increased in the PFC, and with advanced age, when the molecular “brakes” on stress signaling are diminished by loss of phosphodiesterases. These mechanisms have also led to pharmacological treatments for stress-related disorders, including guanfacine treatment of childhood trauma, and prazosin treatment of veterans and civilians with post-traumatic stress disorder.

scholarly journals The Pathways between Cortisol-Related Regulation Genes and PTSD Psychotherapy

Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 376
Author(s):  
Ivone Castro-Vale ◽  
Davide Carvalho
Keyword(s):  
Hpa Axis ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Traumatic Event ◽  
Epigenetic Modification ◽  
Pharmacological Treatments ◽  
Post Traumatic Stress ◽  
First Line ◽  
Cardiometabolic Disorders ◽  
Post Traumatic

Post-traumatic stress disorder (PTSD) only develops after exposure to a traumatic event in some individuals. PTSD can be chronic and debilitating, and is associated with co-morbidities such as depression, substance use, and cardiometabolic disorders. One of the most important pathophysiological mechanisms underlying the development of PTSD and its subsequent maintenance is a dysfunctional hypothalamic–pituitary–adrenal (HPA) axis. The corticotrophin-releasing hormone, cortisol, glucocorticoid receptor (GR), and their respective genes are some of the mediators of PTSD’s pathophysiology. Several treatments are available, including medication and psychotherapies, although their success rate is limited. Some pharmacological therapies based on the HPA axis are currently being tested in clinical trials and changes in HPA axis biomarkers have been found to occur in response not only to pharmacological treatments, but also to psychotherapy—including the epigenetic modification of the GR gene. Psychotherapies are considered to be the first line treatments for PTSD in some guidelines, even though they are effective for some, but not for all patients with PTSD. This review aims to address how knowledge of the HPA axis-related genetic makeup can inform and predict the outcomes of psychotherapeutic treatments.

Effects of psychotherapy on regional cerebral blood flow during trauma imagery in patients with post-traumatic stress disorder: a randomized clinical trial

2007 ◽  
Vol 38 (4) ◽  
pp. 543-554 ◽  
Author(s):  
R. J. L. Lindauer ◽  
J. Booij ◽  
J. B. A. Habraken ◽  
E. P. M. van Meijel ◽  
H. B. M. Uylings ◽  
...  
Keyword(s):  
Blood Flow ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Middle Frontal Gyrus ◽  
Post Traumatic Stress ◽  
Prefrontal Cortical ◽  
Post Traumatic ◽  
Cortical Regions ◽  
The Right

BackgroundFunctional brain-imaging studies in post-traumatic stress disorder (PTSD) have suggested functional alterations in temporal and prefrontal cortical regions. Effects of psychotherapy on these brain regions have not yet been examined.MethodTwenty civilian PTSD out-patients and 15 traumatized control subjects were assessed at baseline using psychometric ratings. Cerebral blood flow was measured using trauma script-driven imagery during 99mtechnetium hexamethyl-propylene-amine-oxime single-photon emission computed tomography scanning. All 20 out-patients were randomly assigned to treatment or wait-list conditions. Treatment was brief eclectic psychotherapy (BEP) in 16 weekly individual sessions.ResultsAt baseline, greater activation was found in the right insula and right superior/middle frontal gyrus in the PTSD group than in the control group. PTSD patients treated with BEP significantly improved on all PTSD symptom clusters compared to those on the waiting list. After effective psychotherapy, lower activation was measured in the right middle frontal gyrus, compared to the PTSD patients on the waiting list. Treatment effects on PTSD symptoms correlated positively with activation in the left superior temporal gyrus, and superior/middle frontal gyrus.ConclusionsBEP induced clinical recovery in PTSD patients, and appeared to modulate the functioning of specific PTSD-related sites in the prefrontal cortical regions.

scholarly journals DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Aliza P. Wingo ◽  
Lynn M. Almli ◽  
Jennifer S. Stevens ◽  
Torsten Klengel ◽  
Monica Uddin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Stress Disorder ◽  
Mirna Regulation ◽  
Post Traumatic Stress ◽  
Comorbid Depression ◽  
Genome Wide ◽  
Post Traumatic

Abstract DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.

scholarly journals Sleep Deprivation, a Link Between Post-Traumatic Stress Disorder and Alzheimer’s Disease

2021 ◽  
Vol 79 (4) ◽  
pp. 1443-1449
Author(s):  
Vedad Delic ◽  
Whitney A. Ratliff ◽  
Bruce A. Citron
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Deprivation ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Stress Disorder ◽  
Tau Proteins ◽  
Post Traumatic Stress ◽  
Post Traumatic

An estimated 5 million Americans are living with Alzheimer's disease (AD), and there is also a significant impact on caregivers, with an additional 16 million Americans providing unpaid care for individuals with AD and other dementias. These numbers are projected to increase in the coming years. While AD is still without a cure, continued research efforts have led to better understanding of pathology and potential risk factors that could be exploited to slow disease progression. A bidirectional relationship between sleep deprivation and AD has been suggested and is well supported by both human and animal studies. Even brief episodes of inadequate sleep have been shown to cause an increase in amyloidβ and tau proteins, both well-established contributors toAD pathology. Sleep deprivation is also the most common consequence of post-traumatic stress disorder (PTSD). Patients with PTSD frequently present with sleep disturbances and also develop dementia at twice the rate of the general population accounting for a disproportionate representation of AD among U.S. Veterans. The goal of this review is to highlight the relationship triad between sleep deprivation, AD, and PTSD as well as their impact on molecular mechanisms driving AD pathology.

scholarly journals Pharmacological treatment of post-traumatic stress disorder

2007 ◽  
Vol 13 (2) ◽  
pp. 119-126 ◽  
Author(s):  
Jonathan I. Bisson
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Pharmacological Treatment ◽  
Stress Disorder ◽  
Pharmacological Treatments ◽  
Post Traumatic Stress ◽  
First Line ◽  
Psychological Therapies ◽  
Post Traumatic ◽  
First Line Treatment

Post-traumatic stress disorder (PTSD) causes significant distress and is often associated with markedly reduced functioning. Recent reviews have consistently recommended trauma-focused psychological therapies as a first-line treatment for PTSD. Pharmacological treatments have also been recommended but not as consistently. This article reviews the available trials of the pharmacological treatment of PTSD and discusses their implications.

Pharmacological treatments for adults with post-traumatic stress disorder: A network meta-analysis of comparative efficacy and acceptability

2020 ◽  
Vol 130 ◽  
pp. 412-420 ◽  
Author(s):  
Gabriela de Moraes Costa ◽  
Fabricio Batistin Zanatta ◽  
Patricia Klarmann Ziegelmann ◽  
Alcina Juliana Soares Barros ◽  
Carlos Fernando Mello
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Meta Analysis ◽  
Pharmacological Treatments ◽  
Post Traumatic Stress ◽  
Comparative Efficacy ◽  
Post Traumatic
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