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

Algorithms for CRT-variant of Approximate Greatest Common Divisor Problem

The approximate greatest common divisor problem (ACD) and its variants have been used to construct many cryptographic primitives. In particular, variants of the ACD problem based on Chinese remainder theorem (CRT) are exploited in the constructions of a batch fully homomorphic encryption to encrypt multiple messages in one ciphertext. Despite the utility of the CRT-variant scheme, the algorithms to solve its security foundation have not been studied well compared to the original ACD based scheme. In this paper, we propose two algorithms for solving the CCK-ACD problem, which is used to construct a batch fully homomorphic encryption over integers. To achieve the goal, we revisit the orthogonal lattice attack and simultaneous Diophantine approximation algorithm. Both two algorithms take the same time complexity $2^{\tilde{O}(\frac{\gamma}{(\eta-\rho)^2})}$ up to a polynomial factor to solve the CCK-ACD problem for the bit size of samples $\gamma$, secret primes $\eta$, and error bound $\rho$. Compared to Chen and Nguyen\u27s algorithm in Eurocrypt\u27 12, which takes $\tilde{O}(2^{\rho/2})$ complexity, our algorithm gives the first parameter condition related to $\eta$ and $\gamma$ size. We also report the experimental results for our attack upon several parameters. From the results, we can see that our algorithms work well both in theoretical and experimental terms

The Role of Vitamin D in Alzheimer’s Disease: A Transcriptional Regulator of Amyloidopathy and Gliopathy

Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) accumulation and cognitive mental decline. Epidemiological studies have suggested an association between low serum vitamin D levels and an increased risk of AD. Vitamin D regulates gene expression via the vitamin D receptor, a nuclear ligand-dependent transcription factor. However, the molecular mechanism underlying the pathogenic and therapeutic effects of vitamin D on AD is not fully understood yet. To better understand how vitamin D regulates the expression of genes related to AD pathology, first, we induced vitamin D deficiency in 5xFAD mice by providing a vitamin-D-deficient diet and observed the changes in the mRNA level of genes related to Aβ processing, which resulted in an increase in the Aβ load in the brain. The vitamin D-deficient diet also suppressed the expression of genes for microglial Aβ phagocytosis. Interestingly, vitamin D deficiency in the early stage of AD resulted in earlier memory impairment. In addition, we administered vitamin D intraperitoneally to 5xFAD mice with a normal diet and found lower Aβ levels with the suppressed expression of genes for Aβ generation and observed improved memory function, which may be potentially associated with reduced MAO-B expression. These findings strongly suggest the role of vitamin D as a crucial disease-modifying factor that may modulate the amyloid pathology with regard to reducing AD symptoms

Aberrant Gamma-Band Oscillations in Mice with Vitamin D Deficiency: Implications on Schizophrenia and its Cognitive Symptoms

Vitamin D plays an essential role in cognitive functions as well as regulating calcium homeostasis and the immune system. Many epidemiological studies have also shown the close relationship between vitamin D deficiency (VDD) and the risk of schizophrenia. Cortical gamma-band oscillations (GBO) are associated with cognitive functions, such as attention and memory. Patients with schizophrenia show abnormal GBO with increased spontaneous GBO and decreased evoked GBO. However, the direct effect of VDD on GBO remains unknown. Parvalbumin interneurons, which predominantly contribute to the generation of GBO, are surrounded by perineuronal nets (PNN). We sought to investigate the associations among VDD, PNN, and GBO. Here, we injected a viral vector (AAV5-DIO-ChR2-eYFP) into the basal forebrain stereotaxically and implanted electrodes for electroencephalogram (EEG). At baseline, the evoked and spontaneous EEG power at the gamma frequency band was measured in 4-month-old male PV-Cre mice. After six and twenty weeks of vitamin D deficient food administration, the power of GBO was measured in the VDD condition. Next, we injected the chondroitinase ABC (ChABC) enzyme into the frontal cortex to eliminate PNN. We found that the VDD group showed decreased power of both optogenetically- and auditory-evoked GBO, whereas the spontaneous GBO increased. Enzymatic digestion of PNN showed similar changes in GBO. Taken together, we suggest that VDD could result in decreased PNN and, consequently, increase the spontaneous GBO and decrease the evoked GBO, reminiscent of the aberrant GBO in schizophrenia. These results show that VDD might increase the risk of schizophrenia and aggravate the cognitive symptoms of schizophrenia

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.</p

Beneficial Effects of Time-Restricted Eating on Metabolic Diseases: A Systemic Review and Meta-Analysis

Various behavioral and physiological pathways follow a pre-determined, 24 hour cycle known as the circadian rhythm. Metabolic homeostasis is regulated by the circadian rhythm. Time-restricted eating (TRE) is a type of intermittent fasting based on the circadian rhythm. In this study, we aim to analyze systemically the effects of TRE on body weight, body composition, and other metabolic parameters. We reviewed articles from PubMed, EMBASE, and the Cochrane Library to identify clinical trials that compared TRE to a regular diet. We included 19 studies for meta-analysis. Participants following TRE showed significantly reduced body weight (mean difference (MD), &minus;0.90; 95% confidence interval (CI): &minus;1.71 to &minus;0.10) and fat mass (MD: &minus;1.58, 95% CI: &minus;2.64 to &minus;0.51), while preserving fat-free mass (MD, &minus;0.24; 95% CI: &minus;1.15 to 0.67). TRE also showed beneficial effects on cardiometabolic parameters such as blood pressure (systolic BP, MD, &minus;3.07; 95% CI: &minus;5.76 to &minus;0.37), fasting glucose concentration (MD, &minus;2.96; 95% CI, &minus;5.60 to &minus;0.33), and cholesterol profiles (triglycerides, MD: &minus;11.60, 95% CI: &minus;23.30 to &minus;0.27). In conclusion, TRE is a promising therapeutic strategy for controlling weight and improving metabolic dysfunctions in those who are overweight or obese. Further large-scale clinical trials are needed to confirm these findings and the usefulness of TRE

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 β–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, β–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, β–coefficients were 2.514 (1.258 to 3.769) in those aged 2–18 years, 0.630 (0.173 to 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: β–coefficients were 3.067 (2.344 to 3.790) in 19–39 years, 2.051 (1.609 to 2.493) in 40–59 years, and 1.173 (0.820 to 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: β–coefficients were 1.438 (0.065 to 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.</p

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

IntroductionAlthough the association between Alzheimer's disease (AD) and constipation is controversial, its causality and underlying mechanisms remain unknown.ObjectivesTo investigate the potential association between slow gut transit and AD using epidemiological data and a murine model.MethodsWe 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 (Aβ) and other markers were examined using ELISA, qRT-PCR, RNA-seq, and behavioral tests.ResultsConstipation 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 Aβ 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.ConclusionImpaired gut transit may contribute to AD pathogenesis via the gut-brain axis, thus suggesting a cyclical relationship between intestinal barrier disruption and Aβ 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.</p

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.</p