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Parvalbumin interneuron-mediated neural disruption in an animal model of postintensive care syndrome: prevention by fluoxetine.

ABSTRACT: Postintensive care syndrome (PICS) is defined as a new or worsening impairment in cognition, mental health, and physical function after critical illness and persisting beyond hospitalization, which is associated with reduced quality of life and increased mortality. Recently, we have developed a clinically relevant animal model of PICS based on two-hit hypothesis. However, the underlying mechanism remains unclear. Accumulating evidence has demonstrated that hippocampal GABAergic interneuron dysfunction is implicated in various mood disorders induced by stress. Thus, this study investigated the role of hippocampal GABAergic interneurons and relevant neural activities in an animal model of PICS. In addition, we tested whether fluoxetine treatment early following combined stress can prevent these anatomical and behavioral pathologies. In the present study, we confirmed our previous study that this PICS model displayed reproducible anxiety- and depression like behavior and cognitive impairments, which resembles clinical features of human PICS. This behavioral state is accompanied by hippocampal neuroinflammation, reduced parvalbumin (PV) expression, and decreased theta and gamma power. Importantly, chronic fluoxetine treatment reversed most of these abnormities. In summary, our study provides additional evidence that PV interneuron-mediated hippocampal network activity disruption might play a key role in the pathology of PICS, while fluoxetine offers protection via modulation of the hippocampal PV interneuron and relevant network activities.

SUBMITTER: Wang Y

PROVIDER: S-EPMC8034944 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To assess the prevalence of and risk factors for postintensive care syndrome in family (PICS-F) in the COVID-19 era.DesignA single-center retrospective study using questionnaires and telephone calls.SettingAn ICU at St. Luke's International Hospital.PatientsPatients who were treated for COVID-19-related acute respiratory distress syndrome between March 23, 2020, and September 30, 2021, and their family members participated.InterventionsNone.Measurements and main resultsPICS-F refers to the psychologic distress such as anxiety, depression, and posttraumatic stress disorder (PTSD) experienced by the patient's family. The primary outcome was PICS-F occurrence. Furthermore, factors related to PICS-F development were identified using statistical analysis. Of 85 patients with COVID-19 who were admitted to the ICU, 57 family members consented to the study and completed the survey, and 54 family members' data were analyzed. The median age of family members was 53.5 years, 68.5% were female, and 46.3% were spouses. The median age of patients was 55.5 years, and 83.3% were male. During their ICU stay, 68.5% received invasive mechanical ventilation, 11.1% received venovenous extracorporeal membrane oxygenation, and 11.1% underwent tracheostomy. The median ICU and hospital stays were 7 and 22 days, respectively. Overall PICS-F occurred in 33%. Anxiety, depression, and PTSD occurred in 24%, 26%, and 4% of family members, respectively. The prevalence of all three components of PICS-F was 4%. Multivariable analysis showed that Family Satisfaction with the ICU Survey (FS-ICU) scores were independently associated with PICS-F development (odds ratio, 0.941; 95% CI, 0.891-0.983; p = 0.005).ConclusionsOne-third of family members of COVID-19 patients admitted to the ICU had symptoms of PICS-F. These results suggest that measurement of FS-ICU may be helpful as a predictor of PICS-F development. In addition, increasing the level of ICU care satisfaction of the family members may prevent PICS-F.

Project description:To synthesize the available evidence focusing on morbidities in pediatric survivors of critical illness that fall within the defined construct of postintensive care syndrome (PICS) in adults, including physical, neurocognitive and psychological morbidities.A comprehensive search was conducted in MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and CINAHL using controlled vocabulary and key word terms to identify studies reporting characteristics of PICS in pediatric intensive care unit (PICU) patients. Two reviewers independently screened all titles and abstracts and performed data extraction. From the 3176 articles identified in the search, 252 abstracts were identified for full text review and nineteen were identified for inclusion in the review. All studies reporting characteristics of PICS in PICU patients were included in the final synthesis.Nineteen studies meeting inclusion criteria published between 1995 and 2016 were identified and categorized into studies reporting morbidities in each of three categories-physical, neurocognitive and psychological. The majority of included articles reported prospective cohort studies, and there was significant variability in the outcome measures utilized. A synthesis of the studies indicate that morbidities encompassing PICS are well-described in children who have survived critical illness, often resolving over time. Risk factors for development of these morbidities include younger age, lower socioeconomic status, increased number of invasive procedures or interventions, type of illness, and increased benzodiazepine and narcotic administration.PICS-related morbidities impact a significant proportion of children discharged from PICUs. In order to further define PICS in children, more research is needed using standardized tools to better understand the scope and natural history of morbidities after hospital discharge. Improving our understanding of physical, neurocognitive, and psychological morbidities after critical illness in the pediatric population is imperative for designing interventions to improve long-term outcomes in PICU patients.

Project description:Psychologic sequelae after critical illness, part of the postintensive care syndrome, significantly decrease quality of life. A robustly effective treatment intervention is currently lacking. Virtual reality has beneficial effects on several non-ICU-related psychologic disorders. The aim of this study was to explore patient-related determinants of ICU-specific virtual reality, such as the timing of patients' self-reported readiness to initiate virtual reality and the number of desired sessions and safety, and to explore the effects of ICU-specific virtual reality on mental health.DesignA multicenter, randomized controlled feasibility study.SettingICU at a university teaching hospital and a secondary care hospital in Rotterdam, The Netherlands.PatientsConsecutive mechanically ventilated patients with sepsis or septic shock.InterventionsPatients were randomly assigned (1:1) to receive ICU-specific virtual reality (ICU-specific virtual reality group) or exposure to a nature virtual reality environment (control virtual reality group).Measurement and main resultsExplorative outcomes were feasibility, in terms of patient-related determinants, and safety. The effects of ICU-specific virtual reality on the psychologic components of postintensive care syndrome and quality of life were additionally studied. Fifty patients (median age: 61 yr; 21 [42%] female) were included. Patients in the ICU-specific virtual reality group felt ready to initiate the virtual reality intervention 10 days (median, 95% range, 5-21 d) after ICU discharge, and one session (median, 95% range, 1-6) was desired. ICU-specific virtual reality patients experienced higher immersion, cybersickness scores were low, and no changes in vital signs were observed. They also reported reduced posttraumatic stress disorder and depression scores and better mental health from 2 days until 1 month after initial exposure (Short Form-12 Mental Component Scale: ICU-specific virtual reality, 57 [36-67] vs control virtual reality, 47 [26-63]; p < 0.01). Six months after exposure, this effect was still present for posttraumatic stress disorder and depression, but not for mental quality of life.ConclusionsICU-specific virtual reality is a feasible and acceptable novel intervention that could be used during recovery from an episode of critical illness in the ICU. A future, adequately powered study should confirm whether virtual reality is able to improve mental health and quality of life.

Project description:BackgroundFamily members of critically ill patients experience symptoms of postintensive care syndrome-family (PICS-F), including anxiety, depression, and posttraumatic stress disorder. Postintensive care syndrome-family reduces the quality of life of the families of critically ill patients and may impede the recovery of such patients. Cognitive behavioral therapy has become a first-line nonpharmacological treatment of many psychological symptoms and disorders, including anxiety, depression, and posttraumatic stress. With regard to managing mild-to-moderate symptoms, the delivery of cognitive behavioral therapy via mobile technology without input from a clinician has been found to be feasible and well accepted, and its efficacy rivals that of face-to-face therapy.ObjectiveThe purpose of our pilot study is to examine the efficacy of using a smartphone mobile health (mHealth) app to deliver cognitive behavioral therapy and diminish the severity and prevalence of PICS-F symptoms in family members of critically ill patients.MethodsFor our pilot study, 60 family members of critically ill patients will be recruited. A repeated-measures longitudinal study design that involves the randomization of participants to 2 groups (the control and intervention groups) will be used. The intervention group will receive cognitive behavioral therapy, which will be delivered via a smartphone mHealth app. Bandura's social cognitive theory and an emphasis on mental health self-efficacy form the theoretical framework of the study.ResultsRecruitment for the study began in August 2020. Data collection and analysis are expected to be completed by March 2022.ConclusionsThe proposed study represents a novel approach to the treatment of PICS-F symptoms and is an extension of previous work conducted by the research team. The study will be used to plan a fully powered randomized controlled trial.Trial registrationClinicalTrials.gov NCT04316767; https://clinicaltrials.gov/ct2/show/NCT04316767.International registered report identifier (irrid)DERR1-10.2196/30813.

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Parvalbumin interneuron-mediated neural disruption in an animal model of postintensive care syndrome: prevention by fluoxetine.

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