Changes in Relative Glucose Metabolic Rate Following Cortisol Administration in Aging Veterans with Posttraumatic Stress Disorder: An FDG-PET Neuroimaging Study

Yehuda, Rachel; Harvey, Philip D.; Golier, Julia A.; Newmark, R. E.; Bowie, C. R.; Wohltmann, J. J.; Grossman, R. A.; Schmeidler, J.; Hazlett, E. A.; Buchsbaum, M.S.

doi:10.1176/appi.neuropsych.21.2.132

Cited by 18 publications

(16 citation statements)

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“…Broadly, our findings of acute LDH learning improvements are consistent with studies in PTSD 23,24 . Although we did not find improvements in attention and working memory which others have demonstrated 56 , those changes were noted 75 minutes post-LDH in PTSD 21,22 . We did not test during this time frame therefore it is possible that learning remains elevated for some time and that other abilities might be enhanced at that time point.…”

Section: Discussioncontrasting

confidence: 98%

Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men

Rubin¹,

Phan

Keating

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid, nongenomic and slow, genomic mechanisms. Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD, but impairs these abilities in healthy individuals. We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men. Methods In a double-blind, placebo-controlled, cross-over study, we examined the time-dependent effects of a single low dose of hydrocortisone (10mg; LDH) on cognition in 45 HIV-infected men. Participants were randomized to receive either LDH or placebo, and one month later were given the opposite treatment. At each intervention session, cognition was assessed 30 minutes (assessing nongenomic effects) and 4 hours (assessing genomic effects) after pill administration. Self-reported stress/anxiety and cortisol/cytokines in saliva were measured throughout each session. Results Compared to placebo, LDH doubled salivary cortisol levels. Cortisol returned to baseline 4 hours post-administration. At the 30-minute assessment, LDH enhanced verbal learning compared to placebo. Greater increases in cortisol were associated with greater enhancements in verbal learning. LDH did not affect subjective stress/anxiety or any other cognitive outcomes at the 30-minute or 4-hour time point. Conclusion The rapid effects of LDH on verbal learning suggests a nongenomic mechanism by which glucocorticoids can enhance cognition in HIV-infected men. The non-enduring nature of this enhancement may limit its clinical utility, but provides insight into mechanisms underlying the effects of acute glucocorticoids on learning.

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Section: Discussioncontrasting

confidence: 98%

Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men

Rubin¹,

Phan

Keating

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…We have previously shown in a naturalistic, between-group study that dexamethasone administration and parallel reductions in endogenous cortisol levels eliminate exaggerated FPS to danger cues in individuals with PTSD (Jovanovic et al, 2011). Additionally, administration of hydrocortisone, another exogenous GR agonist, prior to fear conditioning impairs eyeblink conditioning in individuals with PTSD (Vythilingam et al, 2006) and normalizes increased amygdala activation in individuals with PTSD as assessed by glucose metabolism PET (Yehuda et al, 2009b). In addition, GR activation facilitates fear memory consolidation (Roozendaal et al, 2009) and GR antagonism attenuates dysregulated fear responses in a rodent model of PTSD (Kohda et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study

Michopoulos

Norrholm

Stevens

et al. 2017

Psychoneuroendocrinology

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Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD− (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p<0.05). However, only PTSD− control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p’s≤ 0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (p<0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD.

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“…2a). Using global measures of hippocampal metabolism, inconsistent results have been found in PTSD 80–82 , which perhaps will be clarified in the future with the use of high-resolution technologies.…”

Section: Metabolic State and Hippocampal Dysfunctionmentioning

confidence: 99%

A pathophysiological framework of hippocampal dysfunction in ageing and disease

et al. 2011

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The hippocampal formation has been implicated in a growing number of disorders, from Alzheimer's disease and cognitive ageing to schizophrenia and depression. How can the hippocampal formation, a complex circuit that spans the temporal lobes, be involved in a range of such phenotypically diverse and mechanistically distinct disorders? Recent neuroimaging findings indicate that these disorders differentially target distinct subregions of the hippocampal circuit. In addition, some disorders are associated with hippocampal hypometabolism, whereas others show evidence of hypermetabolism. Interpreted in the context of the functional and molecular organization of the hippocampal circuit, these observations give rise to a unified pathophysiological framework of hippocampal dysfunction.

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Changes in Relative Glucose Metabolic Rate Following Cortisol Administration in Aging Veterans with Posttraumatic Stress Disorder: An FDG-PET Neuroimaging Study

Cited by 18 publications

References 0 publications

Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men

Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study

A pathophysiological framework of hippocampal dysfunction in ageing and disease

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