Glucocorticoid-based pharmacotherapies preventing PTSD

Florido, Antonio; Velasco, Eric; Monari, Silvia; Cano, Marta; Cardoner, Narcı́s; Sandi, Carmen; Andero, Raül; Pérez-Caballero, Laura

doi:10.1016/j.neuropharm.2022.109344

Cited by 11 publications

(5 citation statements)

References 125 publications

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“…The reasons for their interconnectivity can be multifactorial, including both genetic (e.g., pleiotropy, genetic correlation, and linkage disequilibrium) and nongenetic (e.g., mechanistic effects, where one trait affects the physiological or developmental processes that lead to changes in the other traits) factors. Glucocorticoids-our targeted trait for selectionthrough their genomic and nongenomic effects can regulate hippocampal structure, memory consolidation, and sleep architecture (82,(103)(104)(105)(106)(107). Our own findings support a causal role of glucocorticoids in extinction memory and REMS alterations.…”

Section: Blunted Corticosterone Induces Fear Extinction Deficitssupporting

confidence: 54%

“…Previous studies have shown that glucocorticoids facilitate fear extinction (85,(99)(100)(101)(102). However, only a limited number of studies have tried this intervention with patients with PTSD (103). Our findings underscore the importance of considering interindividual differences in hypothalamic-pituitary-adrenal axis responsiveness when evaluating a clinical strategy and highlight the postextinction phase as a critical time for glucocorticoid administration.…”

Section: Blunted Corticosterone Induces Fear Extinction Deficitsmentioning

confidence: 52%

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Blunted glucocorticoid responsiveness to stress causes behavioral and biological alterations that lead to posttraumatic stress disorder vulnerability

Monari,

Guillot de Suduiraut,

Grosse

et al. 2023

Preprint

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BACKGROUND: Understanding why only a subset of trauma-exposed individuals develop posttraumatic stress disorder (PTSD) is critical for advancing clinical strategies. A few behavioral (deficits in fear extinction) and biological (blunted glucocorticoid levels, small hippocampal size, and rapid-eye movement sleep (REMS) disturbances) traits have been identified as potential vulnerability factors. However, whether and to what extent these traits are interrelated and whether one of them could causally engender the others are not known. METHODS: In a genetically selected rat model of reduced corticosterone responsiveness to stress, we explored PTSD-related biobehavioral traits using ex vivo magnetic resonance imaging, cued fear conditioning, and polysomnographic recordings combined with in vivo photometric measurements. RESULTS: We showed that genetic selection for blunted glucocorticoid responsiveness leads to a correlated multitrait response, including impaired fear extinction, small hippocampal volume, and REMS disturbances, supporting their interrelatedness. Fear extinction deficits and concomitant disruptions in REMS could be normalized through postextinction corticosterone administration, causally implicating glucocorticoid deficiency in two core PTSD-related risk factors and manifestations. Furthermore, reduced REMS was accompanied by higher norepinephrine levels in the hippocampal dentate gyrus that were also reverted by postextinction corticosterone treatment. CONCLUSIONS: Our results indicate a predominant role for glucocorticoid deficiency over the contribution of reduced hippocampal volume in engendering both REMS alterations and associated deficits in fear extinction consolidation, and causally implicate blunted glucocorticoids in sustaining neurophysiological disturbances leading to fear extinction deficits.

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Section: Blunted Corticosterone Induces Fear Extinction Deficitssupporting

confidence: 54%

Section: Blunted Corticosterone Induces Fear Extinction Deficitsmentioning

confidence: 52%

Blunted glucocorticoid responsiveness to stress causes behavioral and biological alterations that lead to posttraumatic stress disorder vulnerability

Monari,

Guillot de Suduiraut,

Grosse

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Another limitation of our study was the lack of precise data characterizing the ICU stay, especially data related to potential painful or discomfort-inducing procedures, as well as the presence of delirium or hallucinations, which may promote PTSD [ 50 ]. We did not collect data regarding sedative drugs, especially the use of benzodiazepines [ 22 ] or the use of physical restraints [ 51 ] considered by some authors as a risk factor for PTSD or glucocorticoids, which could have protective effects on the onset of PTSD after ICU stay [ 52 ]. We also did not measure the overall discomfort score at the end of the ICU stay, which may influence the occurrence of PTSD after ICU stay [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study

Kalfon,

El-Hage,

Geantot

et al. 2024

Crit Care

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Background Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors. Methods This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed. Results Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034). Conclusion Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients. Trial Registration: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019.

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“…Several lines of evidence indicate that corticosterone is an anxiety level modulator [69]. Furthermore, the anxiolytic effect of corticosterone is concomitant with the prevention of impairment in social interaction [70].…”

Section: Discussionmentioning

confidence: 99%

Deep-Brain Subthalamic Nucleus Stimulation Enhances Food-Related Motivation by Influencing Neuroinflammation and Anxiety Levels in a Rat Model of Early-Stage Parkinson’s Disease

Grembecka,

Majkutewicz,

Harackiewicz

et al. 2023

IJMS

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Deep-brain subthalamic nucleus stimulation (DBS-STN) has become a well-established therapeutic option for advanced Parkinson’s disease (PD). While the motor benefits of DBS-STN are widely acknowledged, the neuropsychiatric effects are still being investigated. Beyond its immediate effects on neuronal circuits, emerging research suggests that DBS-STN might also modulate the peripheral inflammation and neuroinflammation. In this work, we assessed the effects of DBS-STN on food-related motivation, food intake pattern, and the level of anxiety and compared them with markers of cellular and immune activation in nigrostriatal and mesolimbic areas in rats with the 6-OHDA model of early PD. To evaluate the potential mechanism of observed effects, we also measured corticosterone concentration in plasma and leukocyte distribution in peripheral blood. We found that DBS-STN applied during neurodegeneration has beneficial effects on food intake pattern and motivation and reduces anxiety. These behavioral effects occur with reduced percentages of IL-6-labeled cells in the ventral tegmental area and substantia nigra pars compacta in the stimulated brain hemisphere. At the same brain structures, the cFos cell activations were confirmed. Simultaneously, the corticosterone plasma concentration was elevated, and the peripheral blood lymphocytes were reduced after DBS-STN. We believe that comprehending the relationship between the effects of DBS-STN on inflammation and its therapeutic results is essential for optimizing DBS therapy in PD.

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Glucocorticoid-based pharmacotherapies preventing PTSD

Cited by 11 publications

References 125 publications

Blunted glucocorticoid responsiveness to stress causes behavioral and biological alterations that lead to posttraumatic stress disorder vulnerability

Blunted glucocorticoid responsiveness to stress causes behavioral and biological alterations that lead to posttraumatic stress disorder vulnerability

Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study

Deep-Brain Subthalamic Nucleus Stimulation Enhances Food-Related Motivation by Influencing Neuroinflammation and Anxiety Levels in a Rat Model of Early-Stage Parkinson’s Disease

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