Mortality and Lithium-Protective Effects after First-Episode Mania Diagnosis in Bipolar Disorder: A Nationwide Retrospective Cohort Study in Taiwan.

INTRODUCTION: This study aimed to estimate all-cause mortality in patients after a first-episode mania (FEM) and examine whether six guideline-recommended medications can reduce mortality. METHODS: The cohort included population-based FEM samples and matched controls from Taiwan, spanning 2007 to 2018. The primary outcomes assessed were all-cause/suicide-related mortality, while the secondary outcome focused on mortality associated with pharmacological treatments. We compared mortality in post-FEM patients and age-/sex-matched controls without any diagnosed bipolar disorders and patients with and without psychopharmacological treatment using Cox regression analysis, respectively. Statistics were presented with time-to-event adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs). RESULTS: The study included 54,092 post-FEM patients and 270,460 controls, totaling 2,467,417 person-years of follow-up. Post-FEM patients had higher risks of all-cause mortality (AHR 2.38, 95% CI: 2.31-2.45) and suicide death (10.80, 5.88-19.84) than controls. Lithium (0.62, 0.55-0.70), divalproex (0.89, 0.83-0.95), and aripiprazole (0.81, 0.66-1.00) were associated with reduced all-cause mortality compared to non-users. There were no significant all-cause mortality differences for quetiapine (0.95, 0.89-1.01), risperidone (0.92, 0.82-1.02), and paliperidone (1.24, 0.88-1.76) users. When accounting for drug action onset times in sensitivity analyses, only lithium significantly reduced all-cause mortality (AHR range 0.65-0.72). There were 35 and 16 suicide deaths in post-FEM patients and controls, respectively. No drug had a significant effect on suicide deaths (lithium: 6; divalproex: 7; aripiprazole: 0; quetiapine: 10; risperidone: 4; paliperidone: 1). CONCLUSION: Post-FEM patients had a higher risk of all-cause/suicide-related mortality, and lithium treatment might reduce all-cause mortality.

Post COVID-19 condition and behavioral manifestations in Taiwanese children.

BACKGROUND: This study investigated the prevalence of post COVID-19 condition (PCC) in Taiwanese children, explored common symptoms and behavioral manifestations in children with PCC, and examined potential associations with parental stress and family functioning. METHODS: A total of 116 children who had contracted COVID-19 and their parents participated. At 1 month after the confirmed COVID-19 infection (baseline), the parents were asked to complete a questionnaire about the post COVID-19 symptoms, the child behavior checklist (CBCL) based on the child's situation, also the impact event scale of COVID-19 (IES-C) and family APGAR based on the parents' own situation. Three months after the confirmed COVID-19 infection, parents were again asked to complete the same questionnaires as they did at baseline. RESULTS: Results showed that 44.8% of the children met the criteria for PCC, with the most common symptoms being sputum/nasal congestion, tiredness and decreased concentration. Children without PCC exhibited a significant decrease in CBCL scores during the 2-month follow-up, while no such decrease was observed in children with PCC. However, no significant correlations were found between the number of post COVID-19 symptoms, behavioral manifestations, parental stress levels, and family functioning. CONCLUSIONS: Children with PCC have a less favorable trajectory in improving their behavioral manifestations. Additionally, in the post-pandemic era, post COVID-19 symptoms in children are not necessarily correlated with parental stress and family functioning. Further research is needed to better understand the long-term implications of PCC in children and its impact on their mental well-being, as well as their families.

Nephrotoxicity of organophosphate flame retardants in patients with chronic kidney disease: A 2-year longitudinal study.

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35-775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060-20.096], p = 0.042; 3.053 [1.075-8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, -8.127--0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2'-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.

Psychological distress and related factors among caregivers of children with attention-deficit/hyperactivity disorder during the COVID-19 pandemic.

The present study examined the relationships of caregiver factors (including caregivers' age, sex and educational year), child-family interactions (caregivers' difficulties in managing children's protective behaviors against COVID-19, learning and daily performance, children's conflict with elders and siblings, and parenting styles), and children's factors (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms) with psychological distress of the caregivers of children with ADHD in the COVID-19 pandemic. This study recruited 252 caregivers of children with ADHD to participate and complete a questionnaire collecting their psychological distress in the COVID-19 pandemic, demographics, difficulties in managing children's protective behaviors against COVID-19, learning and daily performance, and parenting styles as well as children's conflict with elders and siblings, and the ADHD and ODD symptoms. Hierarchical regression models were constructed to examine the factors related to psychological distress among caregivers. Factors across caregiver, child, and child-family interaction dimensions, including children's conflict levels with elders and siblings, inattention symptoms, and caregivers' difficulties in managing children's protective behaviors against COVID-19, learning and daily performance, female sex, and younger age were significantly associated with psychological distress among caregivers in various hierarchical regression models. Health professionals should take the relevant factors identified in this study when developing an intervention to relieve caregivers' psychological distress in the COVID-19 pandemic.

Gut mycobiome dysbiosis and its impact on intestinal permeability in attention-deficit/hyperactivity disorder.

BACKGROUND: Dysbiosis in the gut microbial community might be involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The fungal component of the gut microbiome, namely the mycobiota, is a hyperdiverse group of multicellular eukaryotes that can influence host intestinal permeability. This study therefore aimed to investigate the impact of fungal mycobiome dysbiosis and intestinal permeability on ADHD. METHODS: Faecal samples were collected from 35 children with ADHD and from 35 healthy controls. Total DNA was extracted from the faecal samples and the internal transcribed spacer regions were sequenced using high-throughput next-generation sequencing (NGS). The fungal taxonomic classification was analysed using bioinformatics tools and the differentially expressed fungal species between the ADHD and healthy control groups were identified. An in vitro permeability assay (Caco-2 cell layer) was used to evaluate the biological effects of fungal dysbiosis on intestinal epithelial barrier function. RESULTS: The ß-diversity (the species diversity between two communities), but not α-diversity (the species diversity within a community), reflected the differences in fungal community composition between ADHD and control groups. At the phylum level, the ADHD group displayed a significantly higher abundance of Ascomycota and a significantly lower abundance of Basidiomycota than the healthy control group. At the genus level, the abundance of Candida (especially Candida albicans) was significantly increased in ADHD patients compared to the healthy controls. In addition, the in vitro cell assay revealed that C. albicans secretions significantly enhanced the permeability of Caco-2 cells. CONCLUSIONS: The current study is the first to explore altered gut mycobiome dysbiosis using the NGS platform in ADHD. The findings from this study indicated that dysbiosis of the fungal mycobiome and intestinal permeability might be associated with susceptibility to ADHD.

Interrelationships among growth hormone, thyroid function, and endocrine-disrupting chemicals on the susceptibility to attention-deficit/hyperactivity disorder.

Abnormal growth hormones and thyroid function may be linked to pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Phthalates and bisphenol-A (BPA), two endocrine-disrupting chemicals (EDCs), may affect the human endocrine system. In this study, we aimed to perform a comprehensive investigation of whether growth hormone, thyroid function, and EDCs exhibited differential levels between ADHD patients and healthy controls. In total, 144 children with ADHD and 70 healthy control subjects were enrolled. Their endocrine systems were evaluated using the serum levels of insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and Free T4. The urinary levels of EDCs, including monoethyl phthalate (MEP), mono-methyl phthalate (MMP), monoethylhexyl phthalate (MEHP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), and BPA, were also examined. Patients with ADHD had lower IGF-1 levels than healthy controls (p = 0.003), but we observed no significant difference in IGFBP-3, TSH, T3, T4, or Free T4. Compared to the control group, patients with ADHD demonstrated higher MEHP levels (p = 0.043), MnBP (p = 0.033), and MBzP (p = 0.040). Furthermore, MEHP levels (p < 0.001) and BPA levels (p = 0.041) were negatively correlated with IGF-1 levels, while IGF-1 levels were negatively correlated with principal components consisting of ADHD clinical symptoms and neuropsychological performance variables. We suggest that MEHP exposure may be associated with decreased serum levels of IGF-1 and increased risk of ADHD. The mechanism underlying this association may be important for protecting children from environmental chemicals that adversely affect neurodevelopment.

Stigma, depression, and anxiety among patients with head and neck cancer.

PURPOSE: Patients with head and neck cancer (HNC) are vulnerable to psychiatric comorbidities, particularly anxiety and depression, and also suffer from cancer stigma. This study aimed to comprehensively compare HNC patients' stigma, depression, and anxiety, and elucidate the underlying relationships among them. METHODS: This cross-sectional study recruited inpatients with HNC from a medical center. Measurements included a psychiatric diagnostic interview, the Shame and Stigma Scale (SSS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Explanatory Model Interview Catalogue (EMIC), and stressors of HNC patients. Structural equation modeling was used to establish models of potential mechanisms. RESULTS: Those patients having stressors of worry about health (t = 5.21, p < 0.001), worry about job (t = 2.73, p = 0.007), worry about family (t = 2.25, p = 0.026), or worry about economic problems (t = 2.09, p = 0.038) showed significantly higher SSS score than those having no such stressor. The SSS total score was significantly correlated with HAM-A (r = 0.509, p < 0.001), HAM-D (r = 0.521, p < 0.001), and EMIC (r = 0.532, p < 0.001) scores. Structural equation modeling was used to propose the possible effect of stigma on anxiety (ß = 0.51, p < 0.001), and then the possible effect of anxiety on depression (ß = 0.90, p < 0.001). CONCLUSION: Stigma is significantly correlated with anxiety and depression and might in HNC patients. Proper identification of comorbidities and a reduction of stigma should be advised in mental health efforts among patients with HNC.

Morbidity and Associated Factors of Depressive Disorder in Patients With Parkinson's Disease.

ABSTRACT: Parkinson's disease (PD) is a progressive, neurodegenerative disorder and is commonly comorbid with depression. The aim of this cross-sectional study was to assess morbidity and associated factors of depression in patients with PD. In total, 181 patients with PD were enrolled and assessed using the Mini-International Neuropsychiatric Interview. Of the sample, 51% had at least one psychiatric diagnosis. The most prevalent psychiatric disorder was depressive disorder (27.6%), followed by rapid eye movement sleep behavior disorder (9.9%), insomnia disorder (8.8%), and adjustment disorder (2.8%). Severity of anxiety, suicide risk, and anxiolytics/hypnotics use were factors associated with depressive disorder in PD patients. Furthermore, severity of anxiety was significantly linked with suicide risk. We suggest that use of a standardized structured interview for early detection of depression in PD patients is crucial. Anxiety, anxiolytics/hypnotics use, depression, and suicide risks are interrelated and warrant clinical concerns regarding PD patients.

Multiple types of harassment victimization in adolescents with autism spectrum disorder: Related factors and effects on mental health problems.

BACKGROUND/PURPOSE: This study examined the prevalence and related factors of multiple (two or three) types of harassment victimization, including school bullying, cyberbullying, and teacher harassment, and their cumulative effects on depression, anxiety, self-esteem, and suicidality in adolescents with autism spectrum disorder (ASD) but without intellectual disability. METHODS: A total of 219 adolescents with ASD but without intellectual disability and their parents participated in this study. Their experiences of school bullying, cyberbullying, and teacher harassment were evaluated. The related factors of multiple types of harassment victimization, including demographic characteristics, socio-communicative skills, comorbid attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) symptoms, were examined. Moreover, the effects of multiple types of harassment victimization on depression, anxiety, self-esteem, and suicidality were examined. RESULTS: In total, 20.54% of participants were victims of multiple types of harassment. Hyperactivity or impulsivity and ODD symptoms were positively associated with multiple types of harassment victimization. Adolescents with ASD who experienced multiple types of harassment victimization had higher severities of depression and anxiety and were more likely to have suicidality than nonvictims and those who experienced only one type of harassment victimization. CONCLUSION: Experiencing more than one type of harassment victimization was significantly associated with the development of mental health problems in adolescents with ASD. ODD and hyperactivity/impulsivity symptoms predicted the risk of experiencing multiple types of harassment.

Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta-analysis.

OBJECTIVE: To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose-response meta-analysis were conducted. METHODS: The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (<0.4, 0.4-0.8, and 0.8-1.2 mmol/L). We adopted adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for time to the recurrence of mood episodes having the <0.4 mmol/L group as the reference group. Moreover, we systematically searched for related articles in major databases before January 31, 2021 (PROSPERO: CRD42021235812). We used random-effects modeling to estimate the dose-response relationships between lithium serum levels and recurrence of mood episodes, which were depicted as odds ratios (ORs) with 95% CIs. RESULTS: A total of 1406 participants (cohort: 466; meta-analysis: 940) were included. In the cohort study, the 0.4-0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8-1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose-response meta-analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non-linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L). CONCLUSION: Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4-0.8 mmol/L.

Month of birth and mental disorders: A population-based study and validation using global meta-analysis.

OBJECTIVE: Month of birth (MOB) is associated with specified mental disorders (MDs). However, whether these relationships extend to all MDs remains unclear. We investigate the association using a population-based cohort study and a meta-analysis. METHODS: First, we examined patients with 34 DSM-5-classified MDs in the Taiwan national database. We estimated the relative risk ratios (RR) of each illness in each MOB relative to that in the general population and assessed the periodicity, with six further sensitivity analyses. Second, we searched PubMed, Embase, and Cochrane for related articles through 31 December 2020. We used a random-effects model, pooled RRs with 95% confidence intervals of each MOB from the identified studies, and transformed them from MOB to relative age in a year or season. RESULTS: The cohort included 1,951,777 patients. Except for posttraumatic stress disorder, dissociative disorders, feeding/eating disorders, gender dysphoria, and paraphilic disorders, the other MDs had significant MOB periodicity. The meta-analysis included 51 studies investigating 10 MDs. The youngest age at the start of school owing to MOB was associated with the highest RRs of intellectual disability (1.13), autism (1.05), attention-deficit/hyperactivity disorder (1.13). Winter births had significant risks of schizophrenia (1.04), bipolar I disorder (1.02), and major depressive disorder (1.01), and autumn births had a significant risk of alcohol use disorder (1.02). No significant associations between season of birth and Alzheimer's disease, or eating disorders were found. CONCLUSIONS: MOB is related to the risks of certain MDs. This finding provides a reference for future research on the etiology of MDs.

Prevalence and Associated Factors of Depressive Disorder in Caregivers of Individuals With Parkinson Disease.

OBJECTIVE: Parkinson disease (PD) is a debilitating neurodegenerative disease. Caring for an individual with PD can have a variety of negative physical and psychological effects on caregivers which may challenge their ability to continue in their caretaking role. The aim of this study was to assess the prevalence and associated factors of depressive disorders in caregivers of individuals with PD using standardized instruments. METHODS: This study used a cross-sectional design with consecutive sampling. Study participants were recruited from the neurological ward or neurological outpatient clinic of a medical center from August 2018 to July 2019. Caregivers of persons with PD were enrolled and assessed using the Mini International Neuropsychiatric Interview, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor-Davidson Resilience Scale, and Big Five Inventory-10. RESULTS: Of the 162 caregivers that completed the study, 67.3% (n = 109) were females. The most common psychiatric diagnosis was depressive disorder (11.1%), followed by insomnia disorder (7.4%) and anxiety disorder not otherwise specified (4.3%); 28% of the caregivers had a psychiatric diagnosis. Using logistic regression analysis, it was found that duration of caregiving (odds ratio [OR] = 1.28; 95% CI, 1.05-1.58), severity of anxiety (OR = 1.86; 95% CI, 1.36-2.53), and severity of fatigue (OR = 1.08; 95% CI, 1.01-1.16) were 3 significant associated factors for the development of depression. CONCLUSION: Depression was the most prevalent psychiatric diagnosis in caregivers of people with PD. Early diagnosis of these caregivers is crucial to the offering of suitable support and treatment and might improve caregivers' quality of life.

Montelukast does not increase the risk of attention-deficit/hyperactivity disorder in pediatric asthma patients: A nationwide population-based matched cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been linked to pediatric asthma patients treated with montelukast. This study is the first to use a nationwide health insurance research database (NHIRD) to study whether asthmatic children using montelukast are at an increased risk of ADHD. METHODS: We used data from the Taiwan NHIRD, which is a longitudinal database of one million randomly selected subjects. The enrolled patients were followed up until 2013. Patients younger than and equal to 12 years old with new-onset asthma (ICD-9 CM code 493.X) diagnosed between 1997 and 2013 were enrolled. A multivariate Cox regression analysis was conducted to evaluate the association between montelukast treatment and the risk of ADHD (ICD-9-CM code 314.X). RESULTS: We enrolled a total of 54,487 asthmatic children younger than and equal to 12 years old who had at least one claim of inpatient admission or at least three claims of an ambulatory visit. Montelukast users and match controls were identified by matching age, gender, residence, the comorbidities including allergic rhinitis and atopic dermatitis, admission or emergency department visits due to asthma attack, and index date of starting montelukast in a 1:1 ratio, with 12,806 in the montelukast group and 12,806 in the non-montelukast group. The montelukast group had a similar risk of ADHD (n = 632, 4.94%) as the non-montelukast group (n = 610, 4.76%) [adjusted hazard ratio 1.04; 95% confidence interval, 0.93 to 1.17]. In children treated with montelukast, high cumulative days of montelukast use did not increase the risk of ADHD. CONCLUSION: This nationwide population-based cohort study reveals that asthma children treated with montelukast were not at an increased risk of developing ADHD. Nevertheless, validation of our retrospective survey requires further prospective study.

Contemporary psychiatric intervention for chronic schizophrenia patients incarcerated in a religious asylum in Taiwan.

BACKGROUND/PURPOSE: In 2017, Long-Fa Temple, an illegal religious asylum in Taiwan, was forced to shut down. Hundreds of chronic mentally ill patients were incarcerated there but provided with no modern psychiatric treatment. This study investigated the effectiveness of providing psychiatric intervention for patients subsequently transferred from Long-Fa Temple to a medical center. METHODS: In total, 88 patients (mean age: 57.2 years, 52.3% male) who had been incarcerated at Long-Fa Temple were transferred to a southern medical center. The patients underwent comprehensive biological, psychological, and social treatment for 18 months. The patients were evaluated once a month in terms of their psychotic symptoms, self-care, nutrition status, cognitive function, occupational function, and family function. RESULTS: Regarding the patients' length of stay, 18.2% were incarcerated in Long-Fa Temple for less than 10 years, 21.6% for 10-20 years, and 60.2% for more than 20 years. In terms of psychiatric diagnosis, 98.9% of the patients had been diagnosed with a schizophrenia spectrum disorder. During the 18-month treatment period, negative symptoms decreased significantly, while the patients' self-care ability, nutrition status, cognition, occupational function, and family function all significantly improved over time. Patients who had been incarcerated for less than 10 years demonstrated better improvements in psychotic symptoms, self-care, nutrition status, and cognitive function. CONCLUSION: Contemporary psychiatric intervention is beneficial for chronically untreated mentally ill patients, and the patients who had a shorter duration of illness had a better reserve of recovery. These findings can serve as an important reference for psychiatric intervention in developing countries.

Music-Based Intervention Ameliorates Mecp2-Loss-Mediated Sociability Repression in Mice through the Prefrontal Cortex FNDC5/BDNF Pathway.

Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investigate the mechanism by which music-based interventions compromise sociability impairments in mecp2 null/y mice as an experimental RTT model. Male mecp2 null/y mice and wild-type mice (24 days old) were randomly divided into control, noise, and music-based intervention groups. Mice were exposed to music or noise for 6 h/day for 3 consecutive weeks. Behavioral patterns, including anxiety, spontaneous exploration, and sociability, were characterized using open-field and three-chamber tests. BDNF, TrkB receptor motif, and FNDC5 expression in the prefrontal cortex (PFC), hippocampus, basal ganglia, and amygdala were probed using RT-PCR or immunoblotting. mecp2 null/y mice showed less locomotion in an open field than wild-type mice. The social novelty rather than the sociability of these animals increased following a music-based intervention, suggesting that music influenced the mecp2-deletion-induced social interaction repression rather than motor deficit. Mechanically, the loss of BDNF signaling in the prefrontal cortex and hippocampal regions, but not in the basal ganglia and amygdala, was compromised following the music-based intervention in mecp2 null/y mice, whereas TrkB signaling was not significantly changed in either region. FNDC5 expression in the prefrontal cortex region in mecp2 null/y mice also increased following the music-based intervention. Collective evidence reveals that music-based interventions improve mecp2-loss-induced social dysfunction. BDNF and FNDC5 signaling in the prefrontal cortex region mediates the music-based-intervention promotion of social interactions. This study gives new insight into the mechanisms underlying the improvement of social behaviors in mice suffering from experimental Rett syndrome following a music-based intervention.

Brand-Name Antidepressants Outperform Their Generic Counterparts in Preventing Hospitalization for Depression: The Real-World Evidence from Taiwan.

BACKGROUND: Generic antidepressants are approved on the market based on evidence of bioequivalence to their brand-name versions. We aimed to assess whether generic antidepressants exert equal effectiveness as their brand-name counterparts for treating patients with depressive disorders. METHODS: In a nationwide, population-based cohort in Taiwan from 1997 through 2013, patients with a diagnosis of a depressive disorder aged between 18 and 65 years who were new users of antidepressant drugs were classified into either the brand-name group or the generic group. All patients were followed up until medication discontinuation or the end of the study period. We assessed the risk for hospitalization as a primary outcome and augmentation therapy, daily dose, medication discontinuation, or switching to another antidepressant as secondary outcomes. RESULTS: A total of 277 651 brand-name users (35.8% male; mean age: 41.2 years) and 270 583 generic users (35.8% male; mean age: 41.0 years) were divided into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, escitalopram, citalopram, venlafaxine, mirtazapine, moclobemide, imipramine, and bupropion). We found that patients treated with the generic form of sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine, and bupropion demonstrated significantly higher risks of psychiatric hospitalization (adjusted hazard ratios ranged from 1.20-2.34), compared to their brand-name counterparts. The differences between brand-name antidepressants and their generic counterparts in secondary outcomes varied across different drugs. CONCLUSIONS: Compared to most generic antidepressants, brand-name drugs exhibited more protective effects on psychiatric hospitalization for depressive patients. These findings could serve as an important reference for clinicians when encountering patients with depressive disorder.

Comparative efficacy and acceptability of treatments for restless legs syndrome in end-stage renal disease: a systematic review and network meta-analysis.

BACKGROUND: Restless legs syndrome (RLS) is common in end-stage renal disease (ESRD) patients and impairs health and quality of life significantly. However, the optimal treatment of RLS in ESRD patients is uncertain and less studied compared with idiopathic RLS patients. METHODS: We conducted a systematic review and network meta-analysis to compare the efficacy and acceptability of treatments for RLS in ESRD patients. Randomized controlled trials (RCTs) by February 2019 in the PubMed, Cochrane Library, Embase and ClinicalTrials.gov were reviewed. RLS severity reduction was treated as treatment efficacy, and adverse events were treated as acceptable. Both outcomes were appraised using a random effects model expressed as standardized mean differences and odds ratios with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities to obtain a hierarchy of interventions. RESULTS: A total of 12 RCTs were included, comprising 9 interventions and 498 participants. All the interventions significantly improved RLS severity without critical side effects compared with placebo. Gabapentin achieved the greatest decrease of RLS severity [standardized mean difference (SMD) = 1.95, 95% CI 0.81-3.09 (SUCRA: 79.3%)], despite its frequent adverse events [SMD = 0.18, 95% CI 0.02-1.50 (19.9%)]. The combination therapy of exercise plus dopamine agonist had better efficacy [SMD = 1.60, 95% CI 0.08-3.12 (59.8%)] and acceptability [SMD = 1.41, 95% CI 0.01-142.53 (63.9%)] compared with that of vitamin C plus vitamin E [SMD = 1.50, 95% CI 0.47-2.54 (56.6%); SMD = 0.32, 95% CI 0.04-2.86 (32.5%)]. CONCLUSIONS: This network meta-analysis supports that gabapentin is the most effective treatment for RLS in ESRD patients. Exercise plus dopamine agonist is a favorable combination therapy concerning side effects. Future large RCTs with long-term treatment outcomes are necessary.

Gray matter volume and microRNA levels in patients with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder often characterized by gray matter (GM) volume reductions. MicroRNAs, which participate in regulating gene expression, potentially influence neurodevelopment. This study aimed to explore whether differential GM volume is associated with differential miRNA levels in ADHD patients. We recruited a total of 30 drug-naïve patients with ADHD (mean age 10.6 years) and 25 healthy controls (mean age 10.6 years) that underwent a single session of 3.0-T whole brain structural MRI scanning. RNA samples from the participants' white blood cells were collected to identify the ΔCt values of three miRNAs (miR-30e-5p, miR-126-5p, and miR-140-3p) using the real-time quantitative reverse transcription polymerase chain reaction. In comparison to the control group, ADHD patients demonstrated a significantly lower GM volume in the cingulate gyrus, left middle temporal gyrus, right middle occipital gyrus, left fusiform gyrus, and significantly higher ΔCt values of miR-30e-5p, miR-126-5p, and miR-140-3p. In the ADHD group, the GM volume of cingulate gyrus and left fusiform gyrus was negatively correlated with the ΔCt values of miR-30e-5p, miR-140-3p. The GM volume of left fusiform gyrus was negatively correlated to ADHD behavioral symptoms. Using structural equation modeling (SEM), we observed that the effect of miR-140-3p on hyperactivity/impulsivity symptoms was mediated by left fusiform gyrus. Our findings support that GM volume reduction and miRNA increases may be biomarkers for ADHD in children and adolescents. Expression levels of miRNAs may affect the development of brain structures and further participate in the pathophysiology of ADHD.

Defining cognitive and functional profiles in schizophrenia and affective disorders.

BACKGROUND: Neurocognitive dysfunction is a common symptom of various major psychiatric disorders, including schizophrenia, major depressive disorder (MDD), and bipolar I disorder (BD). In this study, we investigated whether cognitive profiles and daily skill functioning could effectively differentiate between patients with schizophrenia, MDD, and BD. METHOD: In this cross-sectional study, we recruited a total of 63 patients with schizophrenia, 55 patients with MDD, 43 patients with BD, and 92 healthy control subjects. We evaluated participants' cognitive functions and functional capacity using the Brief Assessment of Cognition in Schizophrenia (BACS) and the UCSD Performance-based Skills Assessment, Brief Version (UPSA-B), respectively. Multivariate analysis of covariance was then adopted to determine inter-group differences in BACS and UPSA-B performance. RESULTS: The BACS was capable of differentiating patients with a major psychiatric disorder (schizophrenia, MDD, and BD) from healthy subjects. Furthermore, schizophrenia patients had poorer motor speed performance than patients with affective disorders. The UPSA-B, particularly the financial portion, was able to distinguish schizophrenia patients from other groups. However, we did not observe any differences in UPSA-B performance between patients with mood disorders and the healthy controls. No significant difference between patients with BD and those with MDD were observed in either cognitive function or in functional capacity. The performances of the BACS and the UPSA-B were positively correlated, particularly in the MDD group. CONCLUSION: Considering overall performance, the BACS and the UPSA-B characterize different endophenotyping profiles in the aforementioned four participant groups. Therefore, the results support the need for comprehensive assessments that target both cognitive function and functional capacity for patients with major psychiatric disorders.

Gut microbiota and dietary patterns in children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, but the underlying pathophysiological mechanisms of ADHD remain unclear. Gut microbiota has been recognized to influence brain function and behaviors. Therefore, this study aimed to determine whether imbalanced gut microbiomes identified by a 16S rRNA sequencing approach are involved in the pathophysiology of ADHD. We recruited a total of 30 children with ADHD (mean age: 8.4 years) and a total of 30 healthy controls (mean age: 9.3 years) for this study. The dietary patterns of all participants were assessed with the food frequency questionnaire. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. We found that the gut microbiota communities in ADHD patients showed a significantly higher Shannon index and Chao index than the control subjects. Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between ADHD patients and healthy controls. The relative abundance of Bacteroides coprocola (B. coprocola) was decreased, while the relative abundance of Bacteroides uniformis (B. uniformis), Bacteroides ovatus (B. ovatus), and Sutterella stercoricanis (S. stercoricanis) were increased in the ADHD group. Of all participants, S. stercoricanis demonstrated a significant association with the intake of dairy, nuts/seeds/legumes, ferritin and magnesium. B. ovatus and S. stercoricanis were positively correlated to ADHD symptoms. In conclusion, we suggest that the gut microbiome community is associated with dietary patterns, and linked to the susceptibility to ADHD.