Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC).

BACKGROUND: and purpose: Fatigue is among the most common persistent symptoms following post-acute sequelae of Sars-COV-2 infection (PASC). The current study investigated the potential therapeutic effects of High-Definition transcranial Direct Current Stimulation (HD-tDCS) associated with rehabilitation program for the management of PASC-related fatigue. METHODS: Seventy patients with PASC-related fatigue were randomized to receive 3 mA or sham HD-tDCS targeting the left primary motor cortex (M1) for 30 min paired with a rehabilitation program. Each patient underwent 10 sessions (2 sessions/week) over five weeks. Fatigue was measured as the primary outcome before and after the intervention using the Modified Fatigue Impact Scale (MFIS). Pain level, anxiety severity and quality of life were secondary outcomes assessed, respectively, through the McGill Questionnaire, Hamilton Anxiety Rating Scale (HAM-A) and WHOQOL. RESULTS: Active HD-tDCS resulted in significantly greater reduction in fatigue compared to sham HD-tDCS (mean group MFIS reduction of 22.11 points vs 10.34 points). Distinct effects of HD-tDCS were observed in fatigue domains with greater effect on cognitive (mean group difference 8.29 points; effect size 1.1; 95% CI 3.56-13.01; P < .0001) and psychosocial domains (mean group difference 2.37 points; effect size 1.2; 95% CI 1.34-3.40; P < .0001), with no significant difference between the groups in the physical subscale (mean group difference 0.71 points; effect size 0.1; 95% CI 4.47-5.90; P = .09). Compared to sham, the active HD-tDCS group also had a significant reduction in anxiety (mean group difference 4.88; effect size 0.9; 95% CI 1.93-7.84; P < .0001) and improvement in quality of life (mean group difference 14.80; effect size 0.7; 95% CI 7.87-21.73; P < .0001). There was no significant difference in pain (mean group difference -0.74; no effect size; 95% CI 3.66-5.14; P = .09). CONCLUSION: An intervention with M1 targeted HD-tDCS paired with a rehabilitation program was effective in reducing fatigue and anxiety, while improving quality of life in people with PASC.

Incidence rate of psychiatric disorders in 2020: The pivotal role played by SARS-CoV-2 infection.

IMPORTANCE: The Coronavirus Disease (COVID-19) pandemic has significantly impacted mental health outcomes. While the frequency of anxiety and depressive symptoms has increased in the whole population, the relationship between COVID-19 and new psychiatric diagnoses remains unclear. OBJECTIVE: To compare the population incidence rate of emergence of de novo psychiatric disorders in 2020 compared to the previous years, and to compare the incidence rate of new psychiatric disorder diagnoses between people with vs without COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This study utilized administrative claims data from the Clinformatics® Data Mart database, licensed from Optum®. The study is a cross-sectional analysis that compared the incidence rate of new psychiatric disorders in 2020 vs. 2018 and 2019 in the entire insured population database. Subsequently, the incidence of new psychiatric disorders in people with vs. without COVID-19 during 2020 was analyzed. EXPOSURE: The exposures included diagnosis and severity of COVID-19 infection. MAIN OUTCOMES MEASURES: The dependent variables of interest were the incidence rates of new psychiatric disorders, specifically schizophrenia spectrum disorders, mood disorders, anxiety disorders, and obsessive-compulsive disorder. RESULTS: The population studied included 10,463,672 US adults (mean age 52.83, 52% female) who were unique people for the year of 2020. Incidence of newly diagnosed psychiatric disorders per 1,000 individuals in the 2020 whole population were 28.81 (CI: 28.71, 28.92) for anxiety disorders, 1.04 (CI: 1.02, 1.06) for schizophrenia disorders, 0.42 (CI: 0.41, 0.43) for OCD and 28.85 (CI: 28.75, 28.95) for mood disorders. These rates were not significantly higher than 2018 or 2019. When comparing incidence rates between COVID-19 vs. non-COVID-19 populations in 2020, the rates were significantly higher in the COVID-19 population: 46.89 (CI: 46.24, 47.53) for anxiety, 49.31 (CI: 48.66, 49.97) for mood disorders, 0.57 (CI: 0.50, 0.65) for OCD, and 3.52 (CI: 3.34, 3.70) for schizophrenia. COVID-19 severity was significantly associated with new diagnoses of schizophrenia, anxiety and mood disorders in multivariate analyses. CONCLUSIONS: Compared to 2018 and 2019, in 2020 there was no increased incidence of new psychiatric disorders in the general population based on insurance claims data. Importantly, people with COVID-19 were more likely to be diagnosed with a new psychiatric disorder, most notably disorders with psychosis, indicating a potential association between COVID-19 and mental/brain health.

Shedding light on biological sex differences and microbiota-gut-brain axis: a comprehensive review of its roles in neuropsychiatric disorders.

Women and men are suggested to have differences in vulnerability to neuropsychiatric disorders, including major depressive disorder (MDD), generalized anxiety disorder (GAD), schizophrenia, eating disorders, including anorexia nervosa, and bulimia nervosa, neurodevelopmental disorders, such as autism spectrum disorder (ASD), and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease. Genetic factors and sex hormones are apparently the main mediators of these differences. Recent evidence uncovers that reciprocal interactions between sex-related features (e.g., sex hormones and sex differences in the brain) and gut microbiota could play a role in the development of neuropsychiatric disorders via influencing the gut-brain axis. It is increasingly evident that sex-microbiota-brain interactions take part in the occurrence of neurologic and psychiatric disorders. Accordingly, integrating the existing evidence might help to enlighten the fundamental roles of these interactions in the pathogenesis of neuropsychiatric disorders. In addition, an increased understanding of the biological sex differences on the microbiota-brain may lead to advances in the treatment of neuropsychiatric disorders and increase the potential for precision medicine. This review discusses the effects of sex differences on the brain and gut microbiota and the putative underlying mechanisms of action. Additionally, we discuss the consequences of interactions between sex differences and gut microbiota on the emergence of particular neuropsychiatric disorders.

Analysis of COVID-19 Infection and Mortality Among Patients With Psychiatric Disorders, 2020.

Importance: People with major psychiatric disorders are more likely to have comorbidities associated with worse outcomes of COVID-19. This fact alone could determine greater vulnerability of people with major psychiatric disorders to COVID-19. Objective: To assess the odds of testing positive for and mortality from COVID-19 among and between patients with schizophrenia, mood disorders, anxiety disorders and a reference group in a large national database. Design, Setting, and Participants: This cross-sectional study used an electronic health record data set aggregated from many national sources in the United States and licensed from Optum with current and historical data on patients tested for COVID-19 in 2020. Three psychiatric cohorts (patients with schizophrenia, mood disorders, or anxiety disorders) were compared with a reference group with no major psychiatric conditions. Statistical analysis was performed from March to April 2021. Exposure: The exposures observed include lab-confirmed positivity for COVID-19 and mortality. Main Outcomes and Measures: The odds of testing positive for COVID-19 in 2020 and the odds of death from COVID-19 were measured. Results: The population studied included 2 535 098 unique persons, 3350 with schizophrenia, 26 610 with mood disorders, and 18 550 with anxiety disorders. The mean (SD) age was 44 (23) years; 233 519 were non-Hispanic African American, 1 583 440 were non-Hispanic Caucasian; and 1 580 703 (62%) were female. The schizophrenia cohort (positivity rate: 9.86%; adjusted OR, 0.90 [95% CI, 0.84-0.97]) and the mood disorder cohort (positivity rate: 9.86%; adjusted OR, 0.93 [95% CI, 0.87-0.99]) had a significantly lower rate of positivity than the anxiety disorder cohort (positivity rate: 11.17%; adjusted OR, 1.05 [95% CI, 0.98-1.12) which was closer to the reference group (11.91%). After fully adjusting for demographic factors and comorbid conditions, patients with schizophrenia were nearly 4 times more likely to die from the disease than the reference group (OR, 3.74; 95% CI, 2.66-5.24). The mood disorders COVID-19 cohort had a 2.76 times greater odds of mortality than the reference group (OR, 2.76; 95% CI, 2.00-3.81), and the anxiety disorders cohort had a 2.39 times greater odds of mortality than the reference group (OR, 2.39; 95% CI, 1.68-3.27). Conclusions and Relevance: By examining a large database while controlling for multiple confounding factors such as age, race and ethnicity, and comorbid medical conditions, the present study found that patients with schizophrenia had much increased odds of mortality by COVID-19.