Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.

The association of total pulses with the efficacy of repetitive transcranial magnetic stimulation for treatment-resistant major depression: A dose-response meta-analysis.

AIM: This study aimed to examine dose-effects of total pulses on improvement of depressive symptoms in patients with treatment-resistant depression (TRD) receiving repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (DLPFC). MATERIALS AND METHODS: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, and ClinicalTrial.gov databases were systematically searched. We included randomized, double-blind, placebo-controlled trials (RCT) that used rTMS over left DLPFC in patients with TRD. Excluded studies were non-TRD, non-RCTs, or combined other brain stimulation interventions. The outcome of interest was the difference between rTMS arms and sham controls in improvement of depressive symptoms in a dose-response manner. A random-effects meta-analysis and dose-response meta-analysis(DRMA) was used to examine antidepressant efficacy of rTMS and association with total pulses. RESULTS: We found that rTMS over left DLPFC is superior to sham controls (reported as standardized mean difference[SMD] with 95% confidence interval: 0.77; 0.56-0.98). The best-fitting model of DRMA was bell-shaped (estimated using restricted cubic spline model; R2 =0.42), indicating that higher doses (>26,660 total pulses) were not associated with increased improvement of depressive symptoms. Stimulation frequency(R2 =0.53) and age(R2 =0.51) were significant moderators for the dose-response curve. Furthermore, 15-20 Hz rTMS was superior to 10 Hz rTMS (0.61, 0.15-1.10) when combining all doses. CONCLUSIONS: Our findings suggest higher doses(total pulses) of rTMS were not always associated with increased improvement of depressive symptoms in patients with TRD, and that the dose-response relationship was moderated by stimulation frequency and age. These associations emphasize the importance of determining dosing parameters to achieve maximum efficacy.

Comparisons of Quality, Correctness, and Similarity Between ChatGPT-Generated and Human-Written Abstracts for Basic Research: Cross-Sectional Study.

BACKGROUND: ChatGPT may act as a research assistant to help organize the direction of thinking and summarize research findings. However, few studies have examined the quality, similarity (abstracts being similar to the original one), and accuracy of the abstracts generated by ChatGPT when researchers provide full-text basic research papers. OBJECTIVE: We aimed to assess the applicability of an artificial intelligence (AI) model in generating abstracts for basic preclinical research. METHODS: We selected 30 basic research papers from Nature, Genome Biology, and Biological Psychiatry. Excluding abstracts, we inputted the full text into ChatPDF, an application of a language model based on ChatGPT, and we prompted it to generate abstracts with the same style as used in the original papers. A total of 8 experts were invited to evaluate the quality of these abstracts (based on a Likert scale of 0-10) and identify which abstracts were generated by ChatPDF, using a blind approach. These abstracts were also evaluated for their similarity to the original abstracts and the accuracy of the AI content. RESULTS: The quality of ChatGPT-generated abstracts was lower than that of the actual abstracts (10-point Likert scale: mean 4.72, SD 2.09 vs mean 8.09, SD 1.03; P<.001). The difference in quality was significant in the unstructured format (mean difference -4.33; 95% CI -4.79 to -3.86; P<.001) but minimal in the 4-subheading structured format (mean difference -2.33; 95% CI -2.79 to -1.86). Among the 30 ChatGPT-generated abstracts, 3 showed wrong conclusions, and 10 were identified as AI content. The mean percentage of similarity between the original and the generated abstracts was not high (2.10%-4.40%). The blinded reviewers achieved a 93% (224/240) accuracy rate in guessing which abstracts were written using ChatGPT. CONCLUSIONS: Using ChatGPT to generate a scientific abstract may not lead to issues of similarity when using real full texts written by humans. However, the quality of the ChatGPT-generated abstracts was suboptimal, and their accuracy was not 100%.

Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis.

OBJECTIVE: Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk. METHODS: This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate. RESULTS: With adjustment for age, a three-class model was identified, with 42.7% of participants classified as "low comorbidity class (cluster 1)", 44.2% as "cardiometabolic multimorbidity class (cluster 2)", and 13.1% as "FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract)." The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708-14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281-1.953; p<0.001) in cluster 3. CONCLUSION: Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.

Efficacy and safety of Xiaoyao pills for mild to moderate depression: study protocol for a randomized controlled trial.

BACKGROUND: Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients. METHODS: This study is a multi-centre, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants are assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline (before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks. DISCUSSION: The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN12746343. Registered on September 25, 2020.

Incongruent Expression of Brain-Derived Neurotrophic Factor and Cortisol in Schizophrenia: Results from a Randomized Controlled Trial of Laughter Intervention.

OBJECTIVE: Schizophrenia has been associated with dysfunction of the hypothalamic-pituitary-adrenal axis. Furthermore, alterations in neurotrophic factors might contribute to the pathogenesis of schizophrenia. We aimed to evaluate the effects of a simulated laughter intervention on the levels of cortisol and BDNF and to determine whether the effects associated with simulated laughter could be sustained after discontinuation of the intervention. METHODS: In this randomized controlled study, patients with schizophrenia according to DSM-IV clinical criteria were randomly assigned to receive either 8-week-long simulated laughter intervention (n=32) or treatment-as-usual group (control group, n=27). The serum levels of BDNF and cortisol were measured at baseline, week 8, and four weeks after discontinuation (week 12) of the intervention program. RESULTS: After an 8-week simulated laughter intervention, the laughter group had significantly higher levels of BDNF; however, four weeks after discontinuation of the intervention, the levels of BDNF significantly dropped. Interestingly, the levels of cortisol did not change significantly at week 8, but they were significantly elevated at week 12. The levels of BDNF and cortisol in the control group did not change significantly between week 0 and week 8. CONCLUSION: These findings suggest that the simulated laughter intervention has an early effect on neurogenesis with a significant delayed effect on stress regulation in subjects with schizophrenia.

Perceived social support and depression symptoms in patients with major depressive disorder in Taiwan: An association study.

This study analyzes the association between social support and depression symptoms of inpatients with major depressive disorder. A total of 160 inpatients were recruited from the acute psychiatric ward of a medical center in northern Taiwan between July 1, 2015, and December 31, 2016. Data were analyzed using descriptive statistics, simple linear regression and multiple linear regression. Our results reveal that patient depression level is significantly associated with gender, age, marital status, education, occupation and number of admissions due to depression. Social support is significantly associated with marital status and number of admissions due to depression. The depression symptoms of the patients were significantly and negatively associated with overall perceived social support and perceived social support from family, friends and a significant other. These results could serve as a reference for the clinical practice of clinical specialists and argue for the inclusion of social support as an intervention for patients with depression.

The effectiveness of long-acting injectable antipsychotics versus oral antipsychotics in the maintenance treatment of outpatients with chronic schizophrenia.

OBJECTIVE: To compare the psychiatric service utilization between patients who only received long-acting injectable antipsychotics (LAIAs) and those who only received oral antipsychotics (OAPs) in the maintenance treatment of chronic schizophrenia. METHODS: We constructed a cohort of chronic schizophrenia patients who underwent maintenance treatment from the Taiwan National Health Insurance Research Database in 2011 and followed these patients for 12 months. We included patients who had been diagnosed with schizophrenia for at least 3 years, were not hospitalized in 2011, and had received 1 year of maintenance treatment. Inverse probability of treatment weighting logistic, linear, and negative binomial regression models were used to estimate associated psychiatric services utilization and adjust for covariate imbalances between the LAIAs and OAPs groups. RESULTS: Among 40,194 patients, 948 (2.36%) received only LAIAs and 39,246 (97.64%) received only OAPs. Compared with those who received only OAPs, the sole LAIAs users were associated with a lower percentage of psychiatric hospitalization (8.4% and 5.8%, respectively; odds ratio: 0.63, p < .01), shorter lengths of hospitalization days (82.8 and 65.9, respectively; coefficient [b]: -16.87, p = .03), and fewer emergency room visits (2.3 and 1.8, respectively; b: -0.24, p < .01) per patient. CONCLUSIONS: Chronic schizophrenia patients who received only LAIs had a lower risk of disease relapse and a reduction in psychiatric service utilization than those receiving only OAPs.

Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder.

OBJECTIVE: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). METHODS: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA＋P, n = 57) or DM (30 mg/day, VPA＋DM30, n = 56) or 60 mg/day (VPA＋DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. RESULTS: Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA＋P or VPA＋DM30 treatment. VPA＋DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. CONCLUSION: Hematological molecule levels were lower after long-term treatment with VPA. VPA＋DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

Benzodiazepine-Associated Carcinogenesis: Focus on Lorazepam-Associated Cancer Biomarker Changes in Overweight Individuals.

OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION: Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.

Effects of an 8-Week Aerobic Dance Program on Health-Related Fitness in Patients With Schizophrenia.

BACKGROUND: Both psychiatric symptoms and the side effects of medication significantly affect patients with schizophrenia. These effects frequently result in a sedentary lifestyle and weight gain, which increase the risk of cardiovascular disease and premature death. PURPOSE: This study developed an aerobic dance program for patients with schizophrenia and then evaluated the effect of this program on health-related fitness outcomes. METHODS: An experimental research design was used. Sixty patients with schizophrenia were recruited from a daycare ward and rehabilitation center at a psychiatric hospital in Taiwan. Paticipants were assigned randomly into an experimental group, which received the 8-week aerobic dance program intervention, and a control group, which received no intervention. All of the participants were assessed in terms of the outcome variables, which included bodyweight, body mass index, muscular endurance, flexibility, and cardiorespiratory endurance. These variables were measured before the intervention (pretest) as well as at 8 weeks (posttest) and 12 weeks (follow-up) after the intervention. This study used a generalized linear model with a generalized estimating equation method to account for the dependence of repeated measurements and to explore the effects of the intervention on health-related fitness outcomes. RESULTS: Twenty-six participants were in the experimental group, and 28 were in the control group. Significant between-group differences were observed at posttest and in the follow-up for all of the health-related fitness outcomes with the exception of muscular endurance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study suggests that an 8-week aerobic dance program may be an effective intervention in patients with schizophrenia in terms of improving bodyweight, body mass index, flexibility, and cardiorespiratory endurance for a period of at least 4 months. Furthermore, although muscular endurance was postively affected during the short-term period, the benefits did not extend into the follow-up examination. On the basis of these findings, aerobic dance is recommended as a nonpharmacological intervention for patients with schizophrenia who are in daycare or rehabilitation settings.

Incongruent changes in heart rate variability and body weight after discontinuing aerobic exercise in patients with schizophrenia.

A bidirectional connection exists between obesity and altered heart rate variability (HRV). Schizophrenia has been associated with a high risk of obesity and decreased vagal modulation. Few studies have examined the link between obesity and HRV in patients with schizophrenia. The aim of this study was to investigate the effects of aerobic exercise on body weight and HRV, and if so, whether these effects could be sustained after discontinuation of exercise training. A total of 18 overweight patients with schizophrenia completed an 8-week moderate-intensity aerobic exercise program conducted twice weekly for 50min. Body weight and heart rate variability were measured at baseline, week 8, and 4weeks after discontinuation of exercise training. Compared with the control group (15 overweight patients with schizophrenia without exercise training), the exercise group had reduced 2.3kg at week 8. Furthermore, the exercise program increased the low frequency, high frequency, and low frequency plus high frequency of HRV. However, after discontinuation of the exercise program for 4weeks, the changes in body weight and the HRV parameters diverged. All of the HRV parameters returned to their baseline values, but no change was seen in the reduced body weight. This suggests that HRV analysis is a more sensitive tool to detect health conditions in patients with schizophrenia. Although exercise is an easy and effective way to prevent and improve health problems, mental health providers might have underestimated the benefits of exercise in daily clinical practice. A regular exercise program should be considered as an essential part of treatment strategies for patients with schizophrenia.

Analysing the Unequal Effects of Positive and Negative Information on the Behaviour of Users of a Taiwanese On-Line Bulletin Board.

The impact of social influence causes people to adopt the behaviour of others when interacting with other individuals. The effects of social influence can be direct or indirect. Direct social influence is the result of an individual directly influencing the opinion of another, while indirect social influence is a process taking place when an individual's opinion and behaviour is affected by the availability of information about others' actions. Such indirect effect may exhibit a more significant impact in the on-line community because the internet records not only positive but also negative information, for example on-line written text comments. This study focuses on indirect social influence and examines the effect of preceding information on subsequent users' opinions by fitting statistical models to data collected from an on-line bulletin board. Specifically, the different impacts of information on approval and disapproval comments on subsequent opinions were investigated. Although in an anonymous situation where social influence is assumed to be at minimum, our results demonstrate the tendency of on-line users to adopt both positive and negative information to conform to the neighbouring trend when expressing opinions. Moreover, our results suggest unequal effects of the local approval and disapproval comments in affecting the likelihood of expressing opinions. The impact of neighbouring disapproval densities was stronger than that of neighbouring approval densities on inducing subsequent disapproval relative to approval comments. However, our results suggest no effects of global social influence on subsequent opinion expression.

MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin.

Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.

Efficacy of various combined blood purification techniques for treating patients with non-viral acute liver failure.

We sought to study the clinical efficacy of various combined blood purification techniques in patients with non-viral acute liver failure complicated by multiple organ dysfunction syndrome (MODS). For this purpose, 19 patients diagnosed of mid- or late-stage liver failure with MODS score-4 were randomly divided into 3 treatment groups of PE+HP+CVVHDF, PE+CVVHDF, and HP+CVVHDF, respectively. Pre- and post-treatment heart rate (HR), mean arterial pressure (MAP), arterial blood gases (pH, PaO2, and PaCO2), hepatic function, platelet count, and blood coagulation were determined. The data show significant improvement in HR, MAP, PaO2/FiO2, total bilirubin (TBIL), and alanine aminotransferase (ALT) levels after treatment (P < 0.05). TBIL decreased more significantly after treatment in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.01). Significant improvement in prothrombin time and albumin was observed only in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.05). The decrease of TBIL and improvement of PaO2/FiO2 ratio were more pronounced in PE+HP+CVVHDF than in HP+CVVHDF group (P < 0.05). To conclude, liver function was relatively improved by all the three combined blood purification techniques used; however, PE+HP+CVVHDF approach was found more efficient in the removal of toxic metabolites, especially bilirubin. The data suggest that the combined blood purification techniques used were effective and involved minor side effects.

The changing practice of eating: evidence from UK time diaries, 1975 and 2000.

This paper examines some central themes about change in consumption behaviour through an empirical investigation of the practice of eating. It analyses patterns of food consumption in the UK using time diary data from 1975 and 2000. The practice of eating is decomposed into four component activities which are used to explore systematically the inter-relationships between social processes - such as commodification and temporal fragmentation - and ways of providing and consuming food. It charts the expansion of eating out, the degree to which it substitutes for other eating activities, and the implications of its development for social relations and the temporal organization of daily life. Analysis reveals that food consumption continues to be differentiated along established lines of social division, although the content of those divisions has changed and varies across components of the practice. Increasing commodification of the food chain is documented, but without appearing to have a corrosive impact on household organization or social relationships. While tendencies indicative of temporal fragmentation are revealed, counter-tendencies exist which suggest that the practice of eating is resilient to many forms of external pressure. Finally, the application of a practice-based analytical approach permits critical evaluation of theories of social transformation.