Sex and age disparities in the influence of tobacco smoking on depression: Evidence from the Taiwan Biobank.

INTRODUCTION: The global tobacco epidemic poses a notable challenge to global health due to its association with various tobacco-related diseases. Although tobacco smoking is associated with depression, the exact mechanism by which tobacco smoking increases the risk of depression is unclear. This study explored the potential effects of tobacco smoking on depression. METHODS: We used data in the analysis from the Taiwan Biobank of 27916 individuals recruited from 2015 to 2020. To investigate the associations between tobacco use and depression, the results of the depression-measuring subscale of the Patient Health Questionnaire-4 as well as data on participants' tobacco consumption and other relevant covariates, were analyzed. RESULTS: Participants who smoked were more likely to report depression than those who did not smoke (AOR=1.50; 95% CI: 1.21-1.86). Furthermore, depression was significantly higher in women who smoked than in their male counterparts (females: AOR=1.68; 95% CI: 1.27-2.23, and males: AOR=1.32; 95% CI: 0.96-1.80). Women aged <55 years and who smoked were more likely to report depression, whereas this trend was not observed in those aged ≥55 years (<55 years: AOR=1.75; 95% CI: 1.23-2.48), and ≥55 years: AOR=1.58; 95% CI: 0.97-2.56). CONCLUSIONS: Tobacco smoking is a significant factor associated with depression, particularly in younger women. The increasing prevalence of tobacco use for years among younger women in Taiwan might contribute to shifts in the associations between depression and tobacco use in women.

Differential Impacts of Endogenous Antioxidants on Clinical Symptoms and Cognitive Function in Acute and Chronic Schizophrenia Patients.

BACKGROUND: Impaired antioxidant defense is implicated in the pathophysiology of schizophrenia, and superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) are 3 first-line endogenous antioxidants. Various cognitive functions decline differently during the schizophrenia course. The characteristic roles of the 3 antioxidants in clinical and cognitive profiles in acute and chronic phases of schizophrenia require study. METHODS: We recruited 311 patients with schizophrenia, including 92 acutely exacerbated patients who had been off antipsychotics for at least 2 weeks and 219 chronic patients who had been stable on medication for at least 2 months. Blood SOD, CAT, and GSH levels; clinical symptoms; and 9 cognitive test scores were measured. RESULTS: Blood CAT levels were higher in the acute patients than in the chronic patients, whereas SOD and GSH levels were similar to one another. Higher CAT levels were correlated with less positive symptoms, better working memory and problem solving in the acute phase, and less negative symptoms, less general psychopathology, better global assessment of function, and better cognitive function (in speed of processing, attention, problem solving) in the chronic period. Higher SOD levels were correlated with better global assessment of function in the acute phase and better speed of processing, working memory, and verbal learning and memory in the chronic period. GSH influenced neither clinical nor cognitive manifestations. CONCLUSIONS: This study showed that blood CAT affected different clinical and cognitive domains between acute and chronic stages of schizophrenia, SOD influenced cognitive functions in chronic state, but GSH affected none. Further studies are needed to explore the underlying mechanisms.

Spontaneous Co-Assembly of Cellulose Nanocrystals and TiO2 Nanorods Followed by Calcination to Form Cholesteric Inorganic Nanostructures.

Chiral nanomaterials possess unique electronic, magnetic, and optical properties that are relevant to a wide range of applications including photocatalysis, chiral photonics, and biosensing. A simple, bottom-up method to create chiral, inorganic structures is introduced that involves the co-assembly of TiO2 nanorods with cellulose nanocrystals (CNCs) in water. To guide experimental efforts, a phase diagram was constructed to describe how phase behavior depends on the CNCs/TiO2/H2O composition. A lyotropic cholesteric mesophase was observed to extend over a wide composition range as high as 50 wt % TiO2 nanorods, far exceeding other examples of inorganic nanorods/CNCs co-assembly. Such a high loading enables the fabrication of inorganic, free-standing chiral films through removal of water and calcination. Distinct from the traditional templating method using CNCs, this new approach separates sol-gel synthesis from particle self-assembly using low-cost nanorods.

Influence of Sex Differences on Serum Lipid Profiles among Habitual Coffee Drinkers: Evidence from 23,072 Taiwan Biobank Participants.

The bioactive compounds of coffee are involved in lipid metabolism, and sex differences may play an important role. This study aimed to evaluate the influence of sex differences on serum lipid profiles among habitual coffee drinkers. We conducted a nationwide cross-sectional study of 23,628 adults using data obtained from the Taiwan Biobank database. Adults who drank more than one cup of coffee per day and those who drank less than one cup per day were compared with non-drinkers. After adjusting for baseline demographics and lifestyle, a generalized linear model was used to estimate the change in serum lipid profiles in men and women and in postmenopausal and premenopausal women among different coffee-drinking behaviors. We found that habitual coffee consumption changed the serum lipid profiles of men and women. Further, coffee drinkers had higher serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lower serum triglyceride levels than non-drinkers. Compared with premenopausal women, both men and postmenopausal women had increased serum total cholesterol and low-density lipoprotein cholesterol levels. Menopausal status may play an important role in modulating the effect of habitual coffee intake on dyslipidemia. Moreover, premenopausal women potentially benefit more from habitual coffee drinking than men and postmenopausal women.

The associations between cognitive functions and TSNAX genetic variations in patients with schizophrenia.

BACKGROUND: The translin-associated factor X (TSNAX) gene, located adjacent to the DISC1 gene, has been implicated in schizophrenia. While cognitive impairment determines long-term the functional outcome of schizophrenia, the role of TSNAX in cognitive dysfunction of schizophrenia patients remains elusive. This study aimed to explore the genetic effect of TSNAX on cognitive functions of schizophrenia. METHODS: We recruited 286 chronic schizophrenia patients who had been stabilized with antipsychotics for at least 2 months and genotyped three TSNAX SNPs (rs1630250, rs766288, rs6662926). Clinical symptoms and seven cognitive domains were assessed. The score of cognitive tests was standardized to T score. RESULTS: Clinical symptoms were similar among genotypes of all the three SNPs. The GLM analysis demonstrated that TSNAX genetic polymorphisms influenced cognitive function of schizophrenia patients after adjustment for gender, age, and education. The patients with the rs1630250 C/G genotype performed better than the G/G homozygotes in the Trail Making A (p = 0.034). Those with the rs766288 G/T genotype also performed better than the G/G homozygotes in the Trail Making A (p = 0.012). The patients with the G/G genotype of rs6662926 also performed better than the C/C homozygotes in verbal learning and memory test (p = 0.044). CONCLUSIONS: This study suggests that the TSNAX gene variation may influence the cognitive functions of the patients with schizophrenia.

A 30-Year-Old Woman with an 8-Week History of Anxiety, Depression, Insomnia, and Mild Cognitive Impairment Following COVID-19 Who Responded to Accelerated Bilateral Theta-Burst Transcranial Magnetic Stimulation Over the Prefrontal Cortex.

BACKGROUND This report is of a 30-year-old woman with an 8-week history of anxiety, depression, insomnia, and mild cognitive impairment following COVID-19 infection, who responded to accelerated bilateral theta-burst transcranial magnetic stimulation (TBS) over the prefrontal cortex. CASE REPORT A previously healthy 30-year-old woman visited our psychiatric clinic for symptoms including anxiety, depression, insomnia, and brain fog (mild cognitive impairment) for more than 8 weeks after being diagnosed with COVID-19 on May 9, 2022. Continuous TBS of the right dorsolateral prefrontal cortex (DLPFC), followed by intermittent TBS of the left DLPFC, was performed twice daily over 5 days for a total of 10 sessions. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), and subsets of the Wechsler Memory Scale (WMS)-Third Edition were administered at baseline and at the end of treatment. After 10 sessions of treatment, her BAI, BDI, HAMD, PSQI, WMS-Logical Memory, WMS-Faces, WMS-Verbal Paired Associates, and WMS-Family Pictures scores had improved from 4, 18, 10, 14, 8, 10, 12, and 8, respectively, to 0, 7, 1, 10, 15, 15, 15, and 10, respectively. CONCLUSIONS Accelerated TBS over the bilateral DLPFC may ameliorate long-COVID-associated neuropsychiatric symptoms. Additional trials are warranted to evaluate the effect of neuropsychiatric symptoms following COVID-19.

Accelerated theta-burst transcranial magnetic stimulation of the bilateral dorsolateral prefrontal cortex in a patient with post-traumatic stress disorder and major depressive disorder: Case report.

Background: Theta-burst transcranial magnetic stimulation has demonstrated promising effectiveness as treatment for post-traumatic stress disorder (PTSD) and depression. However, the effect of accelerated theta-burst stimulation (TBS) in comorbid with PTSD and depression remains unknown. Case presentation: We report a case of a 25-year-old woman with PTSD and depression whose symptoms markedly improved after continuous TBS of the right dorsolateral prefrontal cortex (DLPFC) and intermittent TBS (iTBS) over the left DLPFC, and then with 20 min break before the 2nd iTBS session. Conclusions: Accelerated TBS over the bilateral DLPFC may improve severe PTSD and depression. Accelerated TBS may have more improvement of depression symptoms than PTSD symptoms. Further trials are warranted to investigate the effect and safety for patients with complicated PTSD and depression.

Efficacy of Repetitive Transcranial Magnetic Stimulation in Patients With Methamphetamine Use Disorder: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

Background: Repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic potential for treating patients with methamphetamine use disorder (MUD). However, the most effective target and stimulation frequency of rTMS for treating MUD remains unclear. This meta-analysis explored the effect of rTMS on MUD. Methods: In this study, PubMed, Cochrane Systematic Reviews, and the Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blind randomized controlled trials that used rTMS for treating MUD. We used published trials to investigate the efficacy of rTMS in MUD up to March 5, 2022, and pooled studies using a random-effect model to compare rTMS treatment effects. Patients who were diagnosed with MUD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders were recruited. Clinical craving scores between baseline and after rTMS were compared using the standardized mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through a visual inspection of funnel plots and the I2 statistic. Results: We identified seven trials with 462 participants with MUD that met the inclusion criteria. All the studies evaluated craving scores, with rTMS demonstrating a more significant effect than the sham treatment on reducing craving scores (SMD = 0.983, CI = 0.620-1.345, p ≤ 0.001). A subgroup meta-analysis revealed that intermittent theta-burst stimulation (iTBS) had a greater positive effect than 10-Hz rTMS. A metaregression revealed that the SMDs increased with the increase in baseline craving scores, whereas they decreased with the increase in the proportion of men and duration of abstinence. Conclusion: The meta-analysis suggests that rTMS may be associated with treatment effect on craving symptoms in patients with MUD. iTBS may have a greater positive effect on craving reduction than 10-z rTMS.

The Relationship between Habitual Coffee Drinking and the Prevalence of Metabolic Syndrome in Taiwanese Adults: Evidence from the Taiwan Biobank Database.

Previous studies revealed inconsistent results between coffee drinking and metabolic syndrome (MetS). The aim of the study was to evaluate the relationship between habitual coffee drinking and the prevalence of MetS among men and women. We conducted a nationwide, cross-sectional study using 23,073 adults obtained from the Taiwan Biobank database (mean ± SD (range) age, 54.57 ± 0.07 (30-79) years; 8341 men and 14,731 (63.8%) women). Adults who drank more than one cup of coffee per day (n = 5118) and those who drank less than one cup per day (n = 4515) were compared with nondrinkers (n = 13,439). Multivariate logistic regression models were used to evaluate the risk of MetS between the two groups. Separate models were also estimated for sex-stratified and habitual coffee-type-stratified (black coffee (BC), coffee with creamer (CC), and coffee with milk (CM)) subgroup analyses. The MetS diagnosis was based on at least three of the five metabolic abnormalities. Coffee drinkers (≥1 cup/day) had a significantly lower prevalence of MetS than nondrinkers (AOR (95% CI): 0.80 (0.73-0.87)). Women who drank any amount of coffee and any type of coffee were more likely to have a significantly lower prevalence of MetS than nondrinkers. Only men who drank more than one cup of coffee per day or black coffee drinkers were more likely to have a lower prevalence of MetS. Our study results indicate that adults with habitual coffee drinking behaviors of more than one cup per day were associated with a lower prevalence of MetS. Moreover, women could benefit from habitual coffee drinking of all three coffee types, whereas men could only benefit from drinking BC.

Effect of N-methyl-D-aspartate receptor enhancing agents on cognition in dementia: an exploratory systematic review and meta-analysis of randomized controlled trials.

Multiple N-methyl-D-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. However, the results remain inconsistent. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs). Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. The standardized mean difference (SMD) was calculated in each study from the effect size; positive values indicated that NMDA receptor enhancing agent treatment improved cognitive function. Funnel plots and the I2 statistic were evaluated for statistical heterogeneity. Moderators were evaluated using meta-regression. We identified 14 RCTs with 2224 participants meeting the inclusion criteria. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105-0.1900, P = 0.02860). Subgroup meta-analysis showed patients with Alzheimer's Disease and trials using the Alzheimer Disease Assessment Scale-cognitive subscale as the primary outcome had small positive significant effects (SMD = 0.1042, 95% CI 0.0076-0.2007, P = 0.03451; SMD = 0.1267, 95% CI 0.0145-0.2388, P = 0.2686). This exploratory meta-analysis showed a very small, positive, and significant effect on overall cognition function in patients with dementia. Studies with larger samples are needed to evaluate different cognitive domains and phases of dementia.

Defining Environmental Health Literacy.

"Environmental Health Literacy" (EHL) is embraced as important for improving public health by preventing disability and disease from our environment. This study aimed to determine knowledge and skill items identified by Environmental Health (EH) professionals as being associated with EHL and to understand how these items rank by importance. Such a coordinated effort to tease out skills and knowledge needed for EHL had not previously been made. We utilized a mixed-methods approach of semi-structured interviews of 24 EH professionals and a quantitative survey with 275 EH professionals across the United States. Interviews identified 37 skill and 69 knowledge items, which were used to create the survey questions. Survey results indicate 32 knowledge items and six skill items considered essential by >50% of respondents where consensus was reached between professional groups (chi square test: p > 0.05). We further identified six knowledge items, which >70% of EH professionals agreed were essential for EHL. The identification of these knowledge and skill items sets the stage for further research that includes exploring agreement with more diverse stakeholders, developing comprehensive measures of EHL and evaluation of methods and materials designed to improve EHL.

Elucidate multidimensionality of type 1 diabetes mellitus heterogeneity by multifaceted information.

Type 1 diabetes (T1D) is an autoimmune disease. Different factors, including genetics and viruses may contribute to T1D, but the causes of T1D are not fully known, and there is currently no cure. The advent of high-throughput technologies has revolutionized the field of medicine and biology, and analysis of multi-source data along with clinical information has brought a better understanding of the mechanisms behind disease pathogenesis. The aim of this work was the development of a data repository linking clinical information and interactome studies in T1D. To address this goal, we analyzed the electronic health records and online databases of genes, proteins, miRNAs, and pathways to have a global view of T1D. There were common comorbid diseases such as anemia, hypertension, vitreous diseases, renal diseases, and atherosclerosis in the phenotypic disease networks. In the protein-protein interaction network, CASP3 and TNF were date-hub proteins involved in several pathways. Moreover, CTNNB1, IGF1R, and STAT3 were hub proteins, whereas miR-155-5p, miR-34a-5p, miR-23-3p, and miR-20a-5p were hub miRNAs in the gene-miRNA interaction network. Multiple levels of information including genetic, protein, miRNA and clinical data resulted in multiple results, which suggests the complementarity of multiple sources. With the integration of multifaceted information, it will shed light on the mechanisms underlying T1D; the provided data and repository has utility in understanding phenotypic disease networks for the potential development of comorbidities in T1D patients as well as the clues for further research on T1D comorbidities.

Effects of sex, tobacco smoking, and alcohol consumption osteoporosis development: Evidence from Taiwan biobank participants.

INTRODUCTION: Osteoporosis is major public health concern, but the long-term impacts of tobacco and alcohol consumption on its development are unclear. This study analyzed the relationship between tobacco and alcohol use and osteoporosis by using data from the Taiwan Biobank (TWB), established in 2012. METHODS: Participants in TWB were included in our study, with a total of 18394 respondents included for analysis. To investigate the relationship between tobacco and alcohol use and osteoporosis, we surveyed their bone mineral density (BMD), consumption of tobacco and alcohol and other covariate data. RESULTS: We found that participants in the tobacco smoking only group (OR=1.24; 95% CI: 1.08-1.42, p=0.003) and the group that both smoked and consumed alcohol (OR=1.39; 95% CI: 1.09-1.77, p=0.008) were more likely to develop osteoporosis than were participants who neither drank alcohol nor smoked. Menopause is strongly associated with osteoporosis in women, and we found that women who used alcohol or tobacco were not at a significantly higher risk than those in the reference group (tobacco only, OR=1.15; 95% CI: 0.86-1.53, p=0.345; both tobacco and alcohol, OR=0.61; 95% CI: 0.14-2.60, p=0.5040). However, men in these groups were at a significantly higher risk than the reference group (tobacco only, OR=1.26; 95% CI: 1.07-1.48, p=0.006; both tobacco and alcohol, OR=1.32; 95% CI: 1.03-1.70, p=0.030). Menopause was a significant risk factor for osteoporosis (OR=2.46; 95% CI: 1.77-3.41, p<0.001). CONCLUSIONS: The influence of tobacco use on osteoporosis was significant, particularly in men, but the effects of alcohol consumption were equivocal in our study. The interactions between tobacco use, alcohol use, and menopausal status on osteoporosis should be considered in future studies.

Hepatitis C virus and hepatitis B virus in patients with schizophrenia.

ABSTRACT: This study evaluated the severe hepatic outcome (SHO) in patients with schizophrenia and viral hepatitis who received antipsychotics.Using the nationwide Taiwan National Health Insurance Research Database, patients first diagnosed with schizophrenia between 2002 and 2013 were identified. Patients diagnosed with schizophrenia who had viral hepatitis, including hepatitis B virus (HBV) or hepatitis C virus (HCV), were designated as the viral hepatitis group. A control group without viral hepatitis was matched for age, sex, and index year in a 2:1 ratio. Patients with severe hepatic outcomes before enrollment were excluded. The 2 cohorts were observed until December 31, 2013. The primary endpoint was occurrence of a SHO, including liver cancer, liver failure, liver decompensation, or transplantation.Among the 16,365 patients newly diagnosed with schizophrenia between January 2002 and December 2013, we identified 614 patients with viral hepatitis and 1228 matched patients without viral hepatitis. Of these 1842 patients, 41 (2.22%) developed SHOs, including 26 (4.23%) in the viral hepatitis group and 15 (1.22%) in the control group, during the mean follow-up period of 3.71 ±â€Š2.49 years. Cox proportional hazard analysis indicated that the SHO risk increased by 3.58 (95% confidence interval [CI]: 1.859-6.754; P < .001) in patients with schizophrenia and viral hepatitis. Moreover, patients with schizophrenia having HCV had a higher SHO risk than those without viral hepatitis (hazard ratio: 5.07, 95% CI: 1.612-15.956; P < .0001). Patients having both schizophrenia and viral hepatitis, especially HCV, had a higher risk of SHOs.

Plasma d-glutamate levels for detecting mild cognitive impairment and Alzheimer's disease: Machine learning approaches.

BACKGROUND: d-glutamate, which is involved in N-methyl-d-aspartate receptor modulation, may be associated with cognitive ageing. AIMS: This study aimed to use peripheral plasma d-glutamate levels to differentiate patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from healthy individuals and to evaluate its prediction ability using machine learning. METHODS: Overall, 31 healthy controls, 21 patients with MCI and 133 patients with AD were recruited. Serum d-glutamate levels were measured using high-performance liquid chromatography (HPLC). Cognitive deficit severity was assessed using the Clinical Dementia Rating scale and the Mini-Mental Status Examination (MMSE). We employed four machine learning algorithms (support vector machine, logistic regression, random forest and naïve Bayes) to build an optimal predictive model to distinguish patients with MCI or AD from healthy controls. RESULTS: The MCI and AD groups had lower plasma d-glutamate levels (1097.79 ± 283.99 and 785.10 ± 720.06 ng/mL, respectively) compared to healthy controls (1620.08 ± 548.80 ng/mL). The naïve Bayes model and random forest model appeared to be the best models for determining MCI and AD susceptibility, respectively (area under the receiver operating characteristic curve: 0.8207 and 0.7900; sensitivity: 0.8438 and 0.6997; and specificity: 0.8158 and 0.9188, respectively). The total MMSE score was positively correlated with d-glutamate levels (r = 0.368, p < 0.001). Multivariate regression analysis indicated that d-glutamate levels were significantly associated with the total MMSE score (B = 0.003, 95% confidence interval 0.002-0.005, p < 0.001). CONCLUSIONS: Peripheral plasma d-glutamate levels were associated with cognitive impairment and may therefore be a suitable peripheral biomarker for detecting MCI and AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing MCI and AD in outpatient clinics.

The Changes of qEEG Approximate Entropy during Test of Variables of Attention as a Predictor of Major Depressive Disorder.

Evaluating brain function through biosignals remains challenging. Quantitative electroencephalography (qEEG) outcomes have emerged as a potential intermediate biomarker for diagnostic clarification in psychological disorders. The Test of Variables of Attention (TOVA) was combined with qEEG to evaluate biomarkers such as absolute power, relative power, cordance, and approximate entropy from covariance matrix images to predict major depressive disorder (MDD). EEG data from 18 healthy control and 18 MDD patients were monitored during the resting state and TOVA. TOVA was found to provide aspects for the evaluation of MDD beyond resting electroencephalography. The results showed that the prefrontal qEEG theta cordance of the control and MDD groups were significantly different. For comparison, the changes in qEEG approximate entropy (ApEn) patterns observed during TOVA provided features to distinguish between participants with or without MDD. Moreover, ApEn scores during TOVA were a strong predictor of MDD, and the ApEn scores correlated with the Beck Depression Inventory (BDI) scores. Between-group differences in ApEn were more significant for the testing state than for the resting state. Our results provide further understanding for MDD treatment selection and response prediction during TOVA.

Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review.

Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.

Differential Expression of Multiple Disease-Related Protein Groups Induced by Valproic Acid in Human SH-SY5Y Neuroblastoma Cells.

Valproic acid (VPA) is a multifunctional medication used for the treatment of epilepsy, mania associated with bipolar disorder, and migraine. The pharmacological effects of VPA involve a variety of neurotransmitter and cell signaling systems, but the molecular mechanisms underlying its clinical efficacy is to date largely unknown. In this study, we used the isobaric tags for relative and absolute quantitation shotgun proteomic analysis to screen differentially expressed proteins in VPA-treated SH-SY5Y cells. We identified changes in the expression levels of multiple proteins involved in Alzheimer's disease, Parkinson's disease, chromatin remodeling, controlling gene expression via the vitamin D receptor, ribosome biogenesis, ubiquitin-mediated proteolysis, and the mitochondrial oxidative phosphorylation and electron transport chain. Our data indicate that VPA may modulate the differential expression of proteins involved in mitochondrial function and vitamin D receptor-mediated chromatin transcriptional regulation and proteins implicated in the pathogenesis of neurodegenerative diseases.

Efficacy and cognitive effect of sarcosine (N-methylglycine) in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials.

BACKGROUND: Sarcosine (N-methylglycine), a type 1 glycine transporter inhibitor (GlyT1), has shown therapeutic potential for treating schizophrenia; however, studies have reported conflicting results. This meta-analysis aimed to explore the efficacy and cognitive effect of sarcosine for schizophrenia. METHODS: In this study, PubMed, Cochrane Systematic Reviews, and Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blinded randomised controlled trials that used sarcosine for treating schizophrenia. We used the published trials up to November 2019 to investigate the efficacy of sarcosine in schizophrenia. We pooled studies by using a random-effect model for comparing sarcosine treatment effects. Patients who were diagnosed with schizophrenia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition were recruited. Clinical improvement and cognitive function scores between baseline and after sarcosine use were compared using the standardised mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visual inspection of funnel plots and through the I2 statistic. RESULTS: We identified seven trials with 326 participants with schizophrenia meeting the inclusion criteria. All these studies evaluated the overall clinical symptoms, and four of them evaluated overall cognitive functions. Sarcosine use achieved more significant effects than the use of its comparators in relieving overall clinical symptoms (SMD = 0.51, CI = 0.26-0.76, p < 0.01). Moreover, studies with the low Positive and Negative Syndrome Scale range of 70-79 showed significant effect size (ES)s of 0.67 (95% CI: 0.03-1.31, p = 0.04). In addition, trials enrolling patients with stable clinical symptoms had significant ESs: 0.53 (95% CI: 0.21-0.85, p < 0.01). Add-on sarcosine combined with first- and second-generation antipsychotics, except clozapine, had a positive effect. For overall cognitive functions, sarcosine showed a positive but insignificant effect compared with its comparators (SMD = 0.27, CI = -0.06 to 0.60, p = 0.10). The effects were correlated with increased female proportions and decreased illness duration, albeit nonsignificantly. CONCLUSIONS: The meta-analysis suggests that sarcosine may be associated with treatment effect on overall clinical symptoms in patients with schizophrenia but not cognitive functions.