National trends in counseling for stress and depression and COVID-19 pandemic-related factors among adults, 2009-2022: A nationwide study in South Korea: Stress, depression, and pandemic.

To investigate the long-term trends in counseling for stress and depression using data from a nationwide survey in South Korea. We conducted a nationwide serial, large-scale, cross-sectional, survey-based study using data from 2,903,887 Korean adults from the Korea Community Health Survey, 2009-2022. Our study investigated the trends and risk factors for counseling for stress and depression during the pre-pandemic (2009-2019) and pandemic era (2020-2022). The prevalence of counseling for stress and depression increased across pre-pandemic (counseling for stress: ß, 0.217 [95 % CI, 0.194 to 0.241]; counseling for depression: ß, 0.136 [0.118 to 0.154]) and pandemic periods (ß, 0.324 [0.287 to 0.360]; ß, 0.210 [0.182 to 0.239], respectively). The prevalence of counseling for stress and depression showed steeper slopes for increasing trends after the outbreak. In addition, subgroups with female sex, urban residence, lower household income, lower self-rated health, shorter sleep time, and higher worries about contracting COVID-19 were the risk factors associated with the increased prevalence of counseling for stress and depression. Our study analyzed the trends in counseling for stress and depression among over two million South Korean adults in 2009-2022, revealing a significant escalation during the pandemic. These findings emphasize the need for mental health policies to support vulnerable groups during the pandemic.

Risks of alopecia areata in long COVID: Binational population-based cohort studies from South Korea and Japan.

Previous studies have proposed alopecia areata (AA) as a potential outcome of COVID-19 infection among autoimmune diseases, yet the findings might be inconclusive and difficult to generalize due to limited sample sizes and evidence levels. Thus, we aimed to investigate in detail the long-term risk of AA following SARS-CoV-2 infection based on large, binational, general population-based cohort studies. Our study investigated the long-term AA risk after SARS-CoV-2 infection by analyzing bi-national, claim-based cohorts in South Korea and Japan: a Korean nationwide cohort (K-COV-N cohort; discovery cohort; total n = 10 027 506) and a Japanese claims-based cohort (JMDC cohort; validation cohort; total n = 12 218 680). AA was identified based on the international classification of diseases 10th revision code (L63) requiring at least three claims within 1 year. After exposure-driven propensity score matching, SARS-CoV-2 infection was associated with an increased risk of incident AA (aHR, 1.66; 95% CI, 1.38-1.99). This increased risk was observed and persisted for up to 6 months. A similar pattern was observed in the validation cohort. As modifiable factors, severe COVID-19 increased the risk of AA, whereas receiving two or more doses of the COVID-19 vaccine before infection decreased the risk of AA. Through a bi-national cohort study in South Korea and Japan, SARS-CoV-2 infection was associated with an elevated risk for incident AA in the aspect of long COVID.

National trends of allergic diseases and pandemic-related factors among individuals with obesity in South Korea: A nationwide representative serial study, 2005-2021.

Background: Although obesity is known to be related to allergic diseases, few studies have investigated the prevalence of allergic diseases in individuals with obesity, especially during the COVID-19 pandemic. Thus, this study aimed to analyze national trends of allergic diseases among individuals with obesity and sociodemographic factors. Methods: This study used data from the Korea National Health and Nutrition Examination Survey to examine the prevalence of allergic diseases among individuals with obesity in South Korea from 2005 to 2021. A nationally representative sample of 118,275 participants aged over 2 years or above was divided into six groups for analysis. This study used weighted multivariate regression analysis to examine the estimates of related factors. It assessed the weighted odds ratios or ß-coefficients for these factors across different categories, including age, sex, region of residence, education level, household income, and body mass index for the entire population. Results: All allergic diseases showed a general upward trend from 2005 to 2021, but each disease showed different prevalence trends when compared by age. Before the pandemic, those aged ≤39 years had an increasing trend for asthma and AD, but those aged ≥40 years had a decreasing trend. For asthma, ß-coefficients were 0.629 (95 % CI, 0.299 to 0.958) for 19-39 years, -0.245 (-0.450 to -0.040) for 40-59 years, and -0.668 (-1.024 to -0.313) for ≥60 years. For AD, ß-coefficients were 2.514 (1.258-3.769) in those aged 2-18 years, 0.630 (0.173-1.086) in those aged 19-39 years, -0.458 (-0.648 to -0.268) in those aged 40-59 years, and -0.253 (-0.454 to -0.052) in those aged ≥60 years. However, for both asthma and AD, there were no significant changes in prevalence during the pandemic. In the case of AR, trends were different from those of asthma and AD. Before the pandemic, AR showed an increasing trend in those aged ≤39 years and those aged ≥40 years: ß-coefficients were 3.067 (2.344-3.790) in 19-39 years, 2.051 (1.609-2.493) in 40-59 years, and 1.173 (0.820-1.526) in ≥60 years. During the pandemic, there was an increasing trend only among those aged 40-59, with no significant changes in other age groups: ß-coefficients were 1.438 (0.065-2.811) in 40-59 years. Conclusions: From 2005 to 2021, all allergic diseases (asthma, AD, and AR) increased overall, but with different age-related trends. No significant link was found between COVID-19 and allergic diseases, possibly due to preventive measures like mask-wearing and social distancing. Anxiety about accessing healthcare during the pandemic likely contributed to a decline in allergy diagnoses, highlighting the need for comprehensive strategies to manage and prevent allergic diseases.

Global and regional prevalence of polypharmacy and related factors, 1997-2022: An umbrella review.

OBJECTIVE: Limited comprehensive evidence exists on the global prevalence of polypharmacy. This knowledge gap contributes to increased healthcare system costs and related public health concerns. Thus, we aimed to synthesize the current evidence on polypharmacy prevalence and associated factors in the general and older populations using an umbrella review. METHODS: Our primary outcomes were global prevalence and related indicators of polypharmacy. We systematically searched Google Scholar, PubMed/MEDLINE, Embase, and CINAHL for studies published between the inception of each database until April 30, 2023. RESULTS: Eleven meta-analyses incorporating 295 studies and 59,552,762 participants from 41 countries across six continents were identified. The global prevalence of polypharmacy in the general population is 37 %, with higher rates in older individuals (45 %), outpatients (48 %), and inpatients (52 %). North America showed a higher prevalence (52 %) than Asia (36 %) and Europe (36 %). Among frail elderly individuals, the prevalence of polypharmacy is 59 %, with the highest rates in Europe (68 %) and hospital settings (71 %). CONCLUSION: The global prevalence of polypharmacy and its associated factors in older adults present a complex, multifaceted, and conflicting picture. Understanding the prevalence of polypharmacy and its associated factors may help reduce the number of multidrug prescriptions.

Global and regional burden of vaccine-associated facial paralysis, 1967-2023: Findings from the WHO international pharmacovigilance database.

The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.

Machine Learning-Based Prediction of Suicidal Thinking in Adolescents by Derivation and Validation in 3 Independent Worldwide Cohorts: Algorithm Development and Validation Study.

BACKGROUND: Suicide is the second-leading cause of death among adolescents and is associated with clusters of suicides. Despite numerous studies on this preventable cause of death, the focus has primarily been on single nations and traditional statistical methods. OBJECTIVE: This study aims to develop a predictive model for adolescent suicidal thinking using multinational data sets and machine learning (ML). METHODS: We used data from the Korea Youth Risk Behavior Web-based Survey with 566,875 adolescents aged between 13 and 18 years and conducted external validation using the Youth Risk Behavior Survey with 103,874 adolescents and Norway's University National General Survey with 19,574 adolescents. Several tree-based ML models were developed, and feature importance and Shapley additive explanations values were analyzed to identify risk factors for adolescent suicidal thinking. RESULTS: When trained on the Korea Youth Risk Behavior Web-based Survey data from South Korea with a 95% CI, the XGBoost model reported an area under the receiver operating characteristic (AUROC) curve of 90.06% (95% CI 89.97-90.16), displaying superior performance compared to other models. For external validation using the Youth Risk Behavior Survey data from the United States and the University National General Survey from Norway, the XGBoost model achieved AUROCs of 83.09% and 81.27%, respectively. Across all data sets, XGBoost consistently outperformed the other models with the highest AUROC score, and was selected as the optimal model. In terms of predictors of suicidal thinking, feelings of sadness and despair were the most influential, accounting for 57.4% of the impact, followed by stress status at 19.8%. This was followed by age (5.7%), household income (4%), academic achievement (3.4%), sex (2.1%), and others, which contributed less than 2% each. CONCLUSIONS: This study used ML by integrating diverse data sets from 3 countries to address adolescent suicide. The findings highlight the important role of emotional health indicators in predicting suicidal thinking among adolescents. Specifically, sadness and despair were identified as the most significant predictors, followed by stressful conditions and age. These findings emphasize the critical need for early diagnosis and prevention of mental health issues during adolescence.

Prenatal opioid exposure and subsequent risk of neuropsychiatric disorders in children: nationwide birth cohort study in South Korea.

OBJECTIVE: To investigate the potential association between prenatal opioid exposure and the risk of neuropsychiatric disorders in children. DESIGN: Nationwide birth cohort study. SETTING: From 1 January 2009 to 31 December 2020, birth cohort data of pregnant women in South Korea linked to their liveborn infants from the National Health Insurance Service of South Korea were collected. PARTICIPANTS: All 3 251 594 infants (paired mothers, n=2 369 322; age 32.1 years (standard deviation 4.2)) in South Korea from the start of 2010 to the end of 2017, with follow-up from the date of birth until the date of death or 31 December 2020, were included. MAIN OUTCOME MEASURES: Diagnosis of neuropsychiatric disorders in liveborn infants with mental and behaviour disorders (International Classification of Diseases 10th edition codes F00-99). Follow-up continued until the first diagnosis of neuropsychiatric disorder, 31 December 2020 (end of the study period), or the date of death, whichever occurred first. Eight cohorts were created: three cohorts (full unmatched, propensity score matched, and child screening cohorts) were formed, all of which were paired with sibling comparison cohorts, in addition to two more propensity score groups. Multiple subgroup analyses were performed. RESULTS: Of the 3 128 571 infants included (from 2 299 664 mothers), we identified 2 912 559 (51.3% male, 48.7% female) infants with no prenatal opioid exposure and 216 012 (51.2% male, 48.8% female) infants with prenatal opioid exposure. The risk of neuropsychiatric disorders in the child with prenatal opioid exposure was 1.07 (95% confidence interval 1.05 to 1.10) for fully adjusted hazard ratio in the matched cohort, but no significant association was noted in the sibling comparison cohort (hazard ratio 1.00 (0.93 to 1.07)). Prenatal opioid exposure during the first trimester (1.11 (1.07 to 1.15)), higher opioid doses (1.15 (1.09 to 1.21)), and long term opioid use of 60 days or more (1.95 (1.24 to 3.06)) were associated with an increased risk of neuropsychiatric disorders in the child. Prenatal opioid exposure modestly increased the risk of severe neuropsychiatric disorders (1.30 (1.15 to 1.46)), mood disorders, attention deficit hyperactivity disorder, and intellectual disability in the child. CONCLUSIONS: Opioid use during pregnancy was not associated with a substantial increase in the risk of neuropsychiatric disorders in the offspring. A slightly increased risk of neuropsychiatric disorders was observed, but this should not be considered clinically meaningful given the observational nature of the study, and limited to high opioid dose, more than one opioid used, longer duration of exposure, opioid exposure during early pregnancy, and only to some neuropsychiatric disorders.

Prenatal and postnatal factors associated with sudden infant death syndrome: an umbrella review of meta-analyses.

BACKGROUND: Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome (SIDS) effects is lacking. We investigated the risk and protective factors related to SIDS. METHODS: We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors. PubMed/MEDLINE, Embase, EBSCO, and Google Scholar were searched from inception until January 18, 2023. Data extraction, quality assessment, and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines. According to observational evidence, credibility was graded and classified by class and quality of evidence (CE; convincing, highly suggestive, suggestive, weak, or not significant). Our study protocol was registered with PROSPERO (CRD42023458696). The risk and protective factors related to SIDS are presented as equivalent odds ratios (eORs). RESULTS: We identified eight original meta-analyses, including 152 original articles, covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents. Several risk factors, including prenatal drug exposure [eOR = 7.84 (95% CI = 4.81-12.79), CE = highly suggestive], prenatal opioid exposure [9.55 (95% CI = 4.87-18.72), CE = suggestive], prenatal methadone exposure [9.52 (95% CI = 3.34-27.10), CE = weak], prenatal cocaine exposure [4.38 (95% CI = 1.95-9.86), CE = weak], prenatal maternal smoking [2.25 (95% CI = 1.95-2.60), CE = highly suggestive], postnatal maternal smoking [1.97 (95% CI = 1.75-2.22), CE = weak], bed sharing [2.89 (95% CI = 1.81-4.60), CE = weak], and infants found with heads covered by bedclothes after last sleep [11.01 (95% CI = 5.40-22.45), CE = suggestive], were identified. On the other hand, three protective factors, namely, breastfeeding [0.57 (95% CI = 0.39-0.83), CE = non-significant], supine sleeping position [0.48 (95% CI = 0.37-0.63), CE = suggestive], and pacifier use [0.44 (95% CI = 0.30-0.65), CE = weak], were also identified. CONCLUSIONS: Based on the evidence, we propose several risk and protective factors for SIDS. This study suggests the need for further studies on SIDS-related factors supported by weak credibility, no association, or a lack of adequate research.

Opioid use and subsequent delirium risk in patients with advanced cancer in palliative care: a multicenter registry study.

The prevalent use of opioids for pain management in patients with advanced cancer underscores the need for research on their neuropsychiatric impacts, particularly delirium. Therefore, we aimed to investigate the potential association between opioid use and the risk of delirium in patients with advanced cancer admitted to the acute palliative care unit. We conducted a retrospective observational study utilizing a multicenter, patient-based registry cohort by collecting the data from January 1, 2019, to December 31, 2020, in South Korea. All data regarding exposures, outcomes, and covariates were obtained through retrospective chart reviews by a team of specialized medical professionals with expertise in oncology. Full unmatched and 1:1 propensity-score matched cohorts were formed, and stratification analysis was conducted. The primary outcome, delirium, was defined and diagnosed by the DSM-IV. Of the 2,066 patients with advanced cancer, we identified 42.8% (mean [SD] age, 64.4 [13.3] years; 60.8% male) non-opioid users and 57.2% (62.8 [12.5] years; 55.9% male) opioid users, respectively. Opioid use was significantly associated with an increased occurrence of delirium in patients with advanced cancer (OR, 2.02 [95% CI 1.22-3.35]). The risk of delirium in patients with advanced cancer showed increasing trends in a dose-dependent manner. High-dose opioid users showed an increased risk of delirium in patients with advanced cancer compared to non-opioid users (low-dose user: OR, 2.21 [95% CI 1.27-3.84]; high-dose user: OR, 5.75 [95% CI 2.81-11.77]; ratio of OR, 2.60 [95% CI 1.05-6.44]). Patients with old age, male sex, absence of chemotherapy during hospitalization, and non-obese status were more susceptible to increased risk of delirium in patients with cancer. In this multicenter patient-based registry cohort study, we found a significant, dose-dependent association between opioid use and increased risk of delirium in patients with advanced cancer. We also identified specific patient groups more susceptible to delirium. These findings highlight the importance of opioid prescription in these patients with advanced cancer, balancing effective doses for pain management and adverse dose-inducing delirium.

Vitamin D Reduces GABA-Positive Astrocytes in the 5xFAD Mouse Model of Alzheimer's Disease.

Background: Vitamin D has neuroprotective and immunomodulating functions that may impact glial cell function in the brain. Previously, we reported molecular and behavioral changes caused by deficiency and supplementation of vitamin D in an Alzheimer's disease (AD) mouse model. Recent studies have highlighted reactive astrocytes as a new therapeutic target for AD treatment. However, the mechanisms underlying the therapeutic effects of vitamin D on the glial cells of AD remain unclear. Objective: To investigate the potential association between vitamin D deficiency/supplementation and the pathological progression of AD, including amyloid-ß (Aß) pathology and reactive astrogliosis. Methods: Transgenic hemizygous 5XFAD male mice were subjected to different dietary interventions and intraperitoneal vitamin D injections to examine the effects of vitamin D deficiency and supplementation on AD. Brain tissue was then analyzed using immunohistochemistry for Aß plaques, microglia, and astrocytes, with quantifications performed via ImageJ software. Results: Our results demonstrated that vitamin D deficiency exacerbated Aß plaque formation and increased GABA-positive reactive astrocytes in AD model mice, while vitamin D supplementation ameliorated these effects, leading to a reduction in Aß plaques and GABA-positive astrocytes. Conclusions: Our findings highlight the significant impact of vitamin D status on Aß pathology and reactive astrogliosis, underscoring its potential role in the prevention and treatment of AD. This study provides the first in vivo evidence of the association between vitamin D and reactive astrogliosis in AD model mice, indicating the potential for targeting vitamin D levels as a novel therapeutic approach for AD.

Sleep, mood disorders, and the ketogenic diet: potential therapeutic targets for bipolar disorder and schizophrenia.

Bipolar disorder and schizophrenia are serious psychiatric conditions that cause a significant reduction in quality of life and shortened life expectancy. Treatments including medications and psychosocial support exist, but many people with these disorders still struggle to participate in society and some are resistant to current therapies. Although the exact pathophysiology of bipolar disorder and schizophrenia remains unclear, increasing evidence supports the role of oxidative stress and redox dysregulation as underlying mechanisms. Oxidative stress is an imbalance between the production of reactive oxygen species generated by metabolic processes and antioxidant systems that can cause damage to lipids, proteins, and DNA. Sleep is a critical regulator of metabolic homeostasis and oxidative stress. Disruption of sleep and circadian rhythms contribute to the onset and progression of bipolar disorder and schizophrenia and these disorders often coexist with sleep disorders. Furthermore, sleep deprivation has been associated with increased oxidative stress and worsening mood symptoms. Dysfunctional brain metabolism can be improved by fatty acid derived ketones as the brain readily uses both ketones and glucose as fuel. Ketones have been helpful in many neurological disorders including epilepsy and Alzheimer's disease. Recent clinical trials using the ketogenic diet suggest positive improvement in symptoms for bipolar disorder and schizophrenia as well. The improvement in psychiatric symptoms from the ketogenic diet is thought to be linked, in part, to restoration of mitochondrial function. These findings encourage further randomized controlled clinical trials, as well as biochemical and mechanistic investigation into the role of metabolism and sleep in psychiatric disorders. This narrative review seeks to clarify the intricate relationship between brain metabolism, sleep, and psychiatric disorders. The review will delve into the initial promising effects of the ketogenic diet on mood stability, examining evidence from both human and animal models of bipolar disorder and schizophrenia. The article concludes with a summary of the current state of affairs and encouragement for future research focused on the role of metabolism and sleep in mood disorders.

National Trends and Prevalence of Atopic Dermatitis and Pandemic-Related Factors among Korean Adults, 2007-2021.

INTRODUCTION: Previous studies have variably reported inconclusive trends in the prevalence of atopic dermatitis (AD) among adults, and there are limited data on the impact of the COVID-19 pandemic. We aimed to investigate the national trends and age-stratified prevalence of AD among adults from 2007 to 2021 in South Korea, focusing mainly on the impact of the COVID-19 pandemic-related factors. METHODS: A nationwide cross-sectional study was conducted using the Korea National Health and Nutrition Examination Survey data from 2007 to 2021. Overall and age-stratified prevalence for AD were assessed using weighted beta coefficients or odds ratios. RESULTS: A total of 83,566 adults over 20 years (male, 49.40%) were included. During the observation period, the prevalence of AD was stable in the overall population from 2.61% (95% CI, 2.29-2.93) in 2007-2009 to 2.15% (1.68-2.63) in 2020 and 2.38% (1.81-2.95) in 2021. However, the weighted prevalence of AD in adults aged 40-59 years old decreased during the pre-pandemic era, and the prevalence of AD in adults aged above 60 years significantly decreased during the pandemic, with a significant decline observed after the initial outbreak. From age-stratification analysis, the adults aged 40-59 years showed a significant increase after the pandemic outbreak which was evident in specific variables: individuals with rural residence, lower education, and lower household income quartiles. Adults aged above 60 years showed a significant decrease in the slope after the outbreak, evident in specific variables: individuals of female, rural residence, lower education, and lower household income quartiles. CONCLUSION: We observed a stable overall prevalence of AD throughout the 15-year observation period. However, the age-stratified analysis suggested significantly different trends according to age-stratified groups and the impact of the COVID-19 pandemic on the prevalence of AD.

Sleep disturbance correlated with severity of neuropathic pain in sciatic nerve crush injury model.

The association between sleep and pain has been investigated widely. However, inconsistent results from animal studies compared with human data show the need for a validated animal model in the sleep-pain association field. Our study aims to validate common neuropathic pain models as a tool for evaluating the sleep-pain association. Electrodes electroencephalogram (EEG) and electromyogram (EMG) were surgically implanted to measure sleep. The von Frey test was used to measure pain sensitivity. Following the baseline data acquisition, two pain-modelling procedures were performed: sciatic nerve crush injury (SCI) and common peroneal nerve ligation (CPL). Post-injury measurements were performed on days 1, 5, 10, and 15 post-surgery. The results presented decreased paw withdrawal thresholds and reduced NREM sleep duration in both models on the first post-surgery day. In the SCI model, NREM sleep duration was negatively correlated with paw withdrawal thresholds (p = 0.0466), but not in the CPL model. Wake alpha and theta EEG powers were also correlated with the pain threshold. The results confirm that the SCI model shows disturbed sleep patterns associated with increased pain sensitivity, suggesting it is a reliable tool for investigating sleep disturbances associated with neuropathic pain.

Slow gut transit increases the risk of Alzheimer's disease: An integrated study of the bi-national cohort in South Korea and Japan and Alzheimer's disease model mice.

INTRODUCTION: Although the association between Alzheimer's disease (AD) and constipation is controversial, its causality and underlying mechanisms remain unknown. OBJECTIVES: To investigate the potential association between slow gut transit and AD using epidemiological data and a murine model. METHODS: We conducted a bi-national cohort study in South Korea (discovery cohort, N=3,130,193) and Japan (validation cohort, N=4,379,285) during the pre-observation period to determine the previous diagnostic history (2009-2010) and the follow-up period (2011-2021). To evaluate the causality, we induced slow gut transit using loperamide in 5xFAD transgenic mice. Changes in amyloid-beta (Aß) and other markers were examined using ELISA, qRT-PCR, RNA-seq, and behavioral tests. RESULTS: Constipation was associated with an increased risk of AD in the discovery cohort (hazard ratio, 2.04; 95% confidence interval [CI], 2.01-2.07) and the validation cohort (hazard ratio; 2.82; 95% CI, 2.61-3.05). We found that loperamide induced slower gut transit in 5xFAD mice, increased Aß and microglia levels in the brain, increased transcription of genes related to norepinephrine secretion and immune responses, and decreased the transcription of defense against bacteria in the colonic tissue. CONCLUSION: Impaired gut transit may contribute to AD pathogenesis via the gut-brain axis, thus suggesting a cyclical relationship between intestinal barrier disruption and Aß accumulation in the brain. We propose that gut transit or motility may be a modifiable lifestyle factor in the prevention of AD, and further clinical investigations are warranted.

Attenuation of homeostatic sleep response and rest-activity circadian rhythm in vitamin D deficient mice.

The link between vitamin D deficiency (VDD) and sleep disturbances has long been suggested. However, the direct causality between VDD, sleep disturbances, and circadian rhythm remains unclear. We aimed to characterize sleep-wake behavior and circadian rhythms in an animal model of VDD. VDD was induced by feeding vitamin D-deficient chow, and we analyzed sleep and circadian rhythm parameters. During light period, VDD mice exhibited reduced wake with more frequent wake bouts and increased NREM sleep time. However, during dark period, the wake EEG power spectrum peaked at theta band frequency, and slow-wave energy was suppressed in mice with VDD. Rest-activity analyses revealed increased circadian period, lower wheel counts, and more frequent and short activity bouts during VDD. Combining sleep and circadian data, we found significantly suppressed activities during the hours with a wake duration shorter than 30 minutes. Moreover, mice in VDD state exhibited a negative correlation between wake theta power and hourly wheel-running counts during dark period. Our data point to a direct link between VDD and disturbances in sleep and rest-activity circadian rhythm, featuring frequent wake bouts during the sleeping phase, reduced sleep pressure build-up in dark period, and reduced activity levels due to increased susceptibility to sleepiness.

National trends in depression and suicide attempts and COVID-19 pandemic-related factors, 1998-2021: A nationwide study in South Korea.

BACKGROUND: Despite the significant psychiatric effects of the COVID-19 pandemic, there's limited data on the prevalence and risk factors of depression and suicide attempts among South Korean adults. METHODS: A nationwide cross-sectional study using the Korea National Health and Nutrition Examination Survey (KNHANES) data from 1998 to 2021 was conducted. Changes in prevalence and risk factors for depression and suicide attempts were assessed using weighted odds ratios or weighted beta coefficients. RESULTS: During the observation period (1998-2021), the prevalence of depression increased in the overall population; however, no significant surge was found regarding the COVID-19 pandemic, from 2.78% (95% CI, 2.41-3.15) in 1998-2005-4.96% (4.32-5.61) in 2020 and 5.06% (4.43-5.69) in 2021. However, immediately after the onset of the pandemic, younger ages, male sex, urban residence, higher education, and high economic status became significant vulnerable factors compared to pre-pandemic periods. The prevalence of suicide attempts remained stable, and there was no notable surge specifically related to the COVID-19 pandemic, from 0.23% (95% CI, 0.18-0.28) in 1998-2005-0.45% (0.25-0.66) in 2020 and 0.42% (0.24-0.60) in 2021. Furthermore, no distinct vulnerable factors associated with suicide attempts have been identified. CONCLUSION: Through this nationwide serial cross-sectional survey study, we emphasized the need for understanding the differential impacts of global crises, such as COVID-19, across varied population subgroups, thereby highlighting the importance of specific and targeted mental health support strategies.

High-fat diet-induced dopaminergic dysregulation induces REM sleep fragmentation and ADHD-like behaviors.

Consumption of a high-fat diet (HFD) has been associated with reduced wakefulness and various behavioral deficits, including anxiety, depression, and anhedonia. The dopaminergic system, which plays a crucial role in sleep and ADHD, is known to be vulnerable to chronic HFD. However, the association between HFD-induced behavioral and molecular changes remains unclear. Therefore, we investigated the effects of a HFD on the dopaminergic system and its association with behavioral deficits in male mice. The mice were divided into normal diet and HFD groups and were analyzed for sleep patterns, behavior tests, and transcription levels of dopamine-related genes in the brain. The HFD group showed decreased wakefulness, increased REM sleep with fragmented patterns, decreased time spent in the center zone of the open field test, shorter immobile time in the tail suspension test, impaired visuospatial memory, and reduced sucrose preference. Additionally, the HFD group had decreased mRNA levels of D1R, COMT, and DAT in the nucleus accumbens, which negatively correlated with REM sleep proportion and REM sleep bout count. The results suggest that HFD-induced behavioral deficits were resemblance to ADHD-like behavioral phenotypes and disturbs REM sleep by dysregulating the dopaminergic system.