Prevalence and risk factors for chronic kidney disease among older adult patients with schizophrenia in Taiwan.

OBJECTIVES: There is an increasing incidence and prevalence of patients with chronic kidney disease (CKD) worldwide. Little is known the prevalence of CKD among older patients with schizophrenia. The purpose of this study was to investigate the prevalence of CKD and its risk factors in older adults with schizophrenia. METHODS: In this cross-sectional study, a convenience sample of 240 patients with schizophrenia age 50 or older were recruited. In addition to demographic and clinical data, participants' estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation based on age, sex, ethnicity, and serum creatinine level determined from a blood sample taken from participants. RESULTS: The overall prevalence of CKD was 11.3%. Those with CKD group were older, had a longer duration of psychiatric illness, a higher body mass index (BMI), and diagnoses of hypertension compared to those in the non-CKD group. Independent of other risk factors, older age and BMI were significantly associated with CKD. CONCLUSIONS: This study found that the overall prevalence of CKD in older patients with schizophrenia was 11.3%. Risk factors for CKD in this population were older age and higher BMI. In addition to early identification and early treatment of CKD in older patients with schizophrenia, clinicians should actively manage the risk factors identified in this study, such as higher BMI and older age.

Associations of urinary phthalate metabolites with household environments among mothers and their preschool-age children.

Phthalates have become a matter of public health concern due to their extensive use worldwide and negative health effects. The evaluation of potential sources of phthalate exposure is crucial to design prevention strategies, especially for vulnerable populations. This study included 528 mother-child pairs in the Taiwan Mother Infant Cohort Study who were followed up at ages 3-6 years between 2016 and 2020. Each mother was interviewed by using a structured questionnaire containing questions on demographic characteristics and household environment factors, such as the use of plastic food packaging, residential visible mold, insecticide sprays, and electric mosquito repellents. Eleven phthalate metabolites were analyzed in urine samples simultaneously collected from the mother-child pairs. The phthalate metabolite urinary concentrations were higher among the children than among their mothers, except those of mono-ethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Multiple linear regression analyses showed that urine samples collected during the summer showed higher concentrations of phthalate metabolites than those collected during the winter. Family income levels had negative associations with the concentrations of MnBP and metabolites of di-2-ethylhexyl phthalate (DEHP) in children. The use of plastic food packaging was positively associated with mono-n-butyl phthalate (MnBP) and metabolites of DEHP in mothers. Residential visible mold or mold stains were significantly associated with higher MnBP and DEHP metabolite concentrations in children. The use of insecticide sprays was positively associated with MnBP concentrations in children. Significant associations between household environmental factors and phthalate exposure were mostly found in children, potentially indicating different exposure pathways between mothers and their children. Findings from this study provide additional information for the design of prevention strategies to protect the health of children and women.

Associations between maternal phthalate exposure and neonatal neurobehaviors: The Taiwan maternal and infant cohort study (TMICS).

Previous studies have shown associations between prenatal phthalate exposure and neurobehavioral changes in children. However, few studies have focused on neonatal neurobehavioral development. This study aimed to examine the associations between prenatal phthalate exposure and neonatal neurobehavioral development in the early days of life after birth. This cohort study included 283 mother-infant pairs who participated in the Taiwan Mother Infant Cohort Study during 2012-2015. Each mother was interviewed, and urine samples were collected during the third trimester of pregnancy (weeks 29-40). Eleven common phthalate metabolites in maternal urine were analyzed. The Chinese version of the Neonatal Neurobehavioral Examination was used to evaluate early infant neurobehavioral development within five days of birth. We performed multiple linear regressions to explore the associations between phthalate exposure and neonatal neurobehavioral development. Sex differences in the association between phthalate metabolites and neonatal neurobehaviors were noted. Among girls, tertiles of phthalate metabolite concentrations were associated with worse behavioral responses and tone and motor patterns in the high-molecular-weight phthalate (HMW) and low-molecular-weight phthalate (LMW) groups. Girls in the highest tertile of di-2-ethylhexyl phthalate (DEHP) and mono-isobutyl phthalate (MiBP) had a negative association with tone and motor patterns. Girls in the highest tertile of mono-n-butyl phthalate (MnBP) and MiBP showed a negative association with behavioral responses. In contrast, tertiles of phthalate metabolite exposure were associated with improved neurobehaviors in mono-methyl phthalate (MMP) among boys. The highest tertile of MMP was positively associated with behavioral responses, primitive reflexes, and tone and motor patterns. Our findings suggest that maternal phthalate exposure affects neonatal neurobehavioral development in a sex-specific manner. Despite the relatively small sample size, our findings add to the existing research linking maternal phthalate exposure to neonatal neurobehavioral development. Additional research is needed to determine the potential long-term effects of prenatal phthalate exposure on children.

Systemic lupus erythematosus and autoimmune features in chronic hospitalized patients with schizophrenia.

OBJECTIVES: Recent studies highlighted the link of schizophrenia risk with genetic variations in complement, which share the same pathogenesis with systemic lupus erythematosus (SLE). However, the coexistence of SLE and schizophrenia were rarely reported. We aimed to explore the autoantibody profiles, complement levels and prevalence of SLE in chronic schizophrenia patients. METHODS: A prospective, cross-sectional study was conducted to recruit 481 long-term hospitalized schizophrenia spectrum disorder patients in Yuli hospital, Taiwan. Severity of schizophrenia was assessed by Positive and Negative Syndrome Scale (PANSS). Immunologic tests of autoantibodies and complement levels were measured. Genome-wide association analysis was conducted to compare genetic variants between schizophrenia with SLE and non-SLE schizophrenia. RESULTS: In total, 47 (9.8%) and 31 (6.4%) participants had positive anti-nuclear antibody (ANA) and anti-double stranded DNA (anti-dsDNA) antibodies, respectively. After rheumatologic exams, 30 (6.2%) patients were diagnosed schizophrenia with SLE, while 32 (6.7%) subjects were classified as schizophrenia with autoimmune features. Schizophrenia patients with SLE had more arthritis, serositis, homogenous ANA pattern, conceptual disorganization in PANSS and increased salivation due to psychotropics compared with their counterparts. ANA titers and complement levels were significantly correlated with PANSS scores and side effect of psychotropics. No significant genetic variation between schizophrenia with SLE and non-SLE schizophrenia were identified. CONCLUSION: SLE may coexist in chronic hospitalized schizophrenia. Complement levels could be a potential biomarker in schizophrenia patients. Considering the possible reversibility of psychotic features and adverse effects of antipsychotics, SLE with psychosis should be identified in patients with chronic hospitalized schizophrenia.

Randomized, double-blind, placebo, and risperidone-controlled study of lurasidone in the treatment of schizophrenia: Results of an inconclusive 6-week trial.

OBJECTIVE: The efficacy and safety of lurasidone in schizophrenia has been demonstrated in multiple controlled trials, primarily in US and European populations. The aim of the current study was To evaluate lurasidone for the treatment of schizophrenia among patients in Japan, Korea, and Taiwan. METHODS: Hospitalized patients (N = 460) with schizophrenia were randomized to 6 weeks of fixed-dose lurasidone 40 mg/d, lurasidone 80 mg/d, risperidone 4 mg/d, or placebo. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). RESULTS: No significant endpoint differences in PANSS total score were found for lurasidone or risperidone vs placebo. Lurasidone was safe and well tolerated, with minimal effects on weight and metabolic parameters. DISCUSSION: The current study was inconclusive regarding the efficacy of lurasidone in schizophrenia but further confirmed its safety and tolerability.

Association between frailty and its individual components with the risk of falls in patients with schizophrenia spectrum disorders.

Frailty is common among older people who carry an increased risk for poor outcomes, including falls, physical disabilities, infections, and mortality. However, the prevalence of frailty and the prognostic influence of frailty status are poorly understood in adults with schizophrenia. The present study aimed to assess the predictive ability of frailty and its individual components for the risk of falls in patients with chronic schizophrenia. Frailty status was assessed at baseline by using Fried frailty criteria after the enrollment of 561 patients with chronic schizophrenia. The patients were followed up for 18 months, and the outcome of the study was the incidence of falls. The mean age of the patients was 53.8 years, and a total of 35.3% were females. One-quarter (25.3%) of patients received typical antipsychotics. The prevalence of frailty was 10.2% at baseline. During follow-up, 40 patients (7.1%) experienced falls. Frailty status was associated with increased susceptibility to falling with an unadjusted hazard ratio of 5.27 (95% confidence interval: 2.75-10.10) and a hazard ratio of 4.65 (95% confidence interval: 1.88-11.54) after multivariate adjustment. Among the components of frailty, the most significant association was observed between low physical activity and falls (p < 0.05). In conclusion, frailty is highly prevalent in patients with chronic schizophrenia and is associated with the risk of adverse clinical events. Further studies are needed to explore the mechanisms underlying the relationship between schizophrenia and frailty in an attempt to develop an appropriate treatment plan for improving clinical outcomes for these patients.

Risk of gastrointestinal Hypomotility in schizophrenia and schizoaffective disorder treated with antipsychotics: A retrospective cohort study.

OBJECTIVE: The risk of gastrointestinal hypomotility (GIHM) with the use of antipsychotic medications in patients with schizophrenia remains inadequately recognized. The aim of this study was to explore the incidence of GIHM and its risks in patients with schizophrenia treated with antipsychotics. METHODS: We conducted a retrospective cohort study using the National Health Insurance Research Database. We identified adult (≥ 20years of age) patients with a first-time diagnosis of schizophrenia or schizoaffective disorder in the Registry for Catastrophic Illness Patients during the period from 2001 to 2011. Each subject in the cohort was followed until their corresponding diagnosis of GIHM was made, until the time of death, or to December 31, 2012. The incidence rates of each outcome were calculated. Cox proportional hazards regression with time-dependent covariates for antipsychotics use was employed to evaluate the associations between different types of antipsychotics and the risk of GIHM. RESULTS: Our study found that the incidence densities of constipation, ileus, and ischemic bowel disease were 42.5, 4.4, and 0.1 per 1000 person-years. In terms of the risk of hypomotility with the use of antipsychotics, clozapine and quetiapine were significant in developing constipation, with a hazard ratio of 2.15 and 1.34, respectively. High-potency first-generation antipsychotics and clozapine were also significant in the occurrence of ileus, with a hazard ratio of 1.30 and 1.95, respectively. Similar associations were found in an anticholinergic agent subgroup analysis. CONCLUSION: Patients receiving antipsychotics such as high-potency first-generation antipsychotics, clozapine, or quetiapine should undergo proper evaluation and intervention to minimize the disease burden and life-threatening outcomes of treatment.

Psychopathology, psychopharmacological properties, decision-making capacity to consent to clinical research and the willingness to participate among long-term hospitalized patients with schizophrenia.

Many studies discuss factors related to the decision-making capacity to consent to clinical research (DMC) of patients with schizophrenia. However, these studies rarely approached willingness to participate and the association between psychopharmacological properties (e.g., antipsychotic-induced side effects) and DMC. This study aimed to explore factors related to DMC and willingness to participate in patients with schizophrenia. All 139 patients with schizophrenia were assessed with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and other measures. A linear regression model was used to find the predictors of MacCAT-CR scores. A logistic regression model was used for exploring the predictors of willingness to participate. Patients with more severe negative symptoms performed poorly in DMC outcomes. In addition, females, those with fewer years of education and reduced cognitive function are more likely to experience difficulties in decision-making. Forty-three subjects (30.4%) chose to participate. Patients with higher level of positive symptoms, longer length of stay, higher burden of anticholinergics and users of atypical antipsychotics were more likely to participate in a clinical study which aimed to "enhance cognition". These finding suggest that research investigators should consider many variables for patients who require more intensive screening for impaired DMC.

Readiness to quit as a predictor for outcomes of smoking-reduction programme with transdermal nicotine patch or bupropion in a sample of 308 patients with schizophrenia.

Readiness to quit has been found to predict smoking-cessation outcomes in a general population. However, little is known about the relationship between the readiness to quit and smoking-reduction outcomes in patients with schizophrenia treated with pharmacological adjuvants. The aim of this study was to examine the association between readiness to quit and smoking-reduction outcomes in patients with schizophrenia. A total of 308 subjects using nicotine replacement therapy (NRT) (N = 242) or bupropion (N = 66) participated in an 8-week smoking-reduction programme. Participants were categorised into precontemplators (N = 127), contemplators (N = 76) and preparators (N = 105) to quit smoking based on the transtheoretical model. There was a significant difference in change in number of cigarettes (NOC) (p = 0.007) and Fagerstrom test for nicotine dependence (FTND) score (nicotine dependence level) (p = 0.029) across the stages of change. A linear regression model revealed trend of increasing reduction in NOC and FTND scores in different stages of change (NOC: B = -1.22, t = -2.81, p = 0.005; FTND: B = -0.43, t = -2.57, p = 0.011). However, the 7-day point prevalence of abstinence was 5.5% (18/308), but there was no significant association between stage of change and smoking cessation (p = 0.26), possibly due to a very small sample size of successful quitters. In summary, among a cohort of institutionalised chronic schizophrenia patients receiving 8-week NRT or bupropion, stage of change can predict smoking reduction and may serve as a useful indicator for patients' preparedness before a trial of smoking reduction.

Rapid development of fatal bowel infarction within 1 week after clozapine treatment: a case report.

Although there have been reported fatalities associated with clozapine-induced bowel infarction, in all of these cases, the patients had taken clozapine for months to years. We present here the case of a 47-year-old single man who died suddenly due to bowel infarction and sepsis 1 week after taking clozapine.

Validation of Chinese version of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) in patients with schizophrenia spectrum disorders.

There is a lack of validated instruments assessing the decision-making capacity to consent to clinical research of patients with schizophrenia spectrum disorders who speak Chinese. This study aimed to determine the validity and reliability of the Chinese version of MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). The MacCAT-CR using a hypothetical study, the Positive and Negative Syndrome Scale (PANSS), the Mini-Mental State Examination (MMSE) assessed 139 patients with schizophrenia or schizoaffective disorder. The Cronbach's alpha coefficient was 0.74. The intra-class coefficients for understanding, appreciation, and reasoning scores ranged from 0.53 to 0.81. Regarding validity, the understanding, appreciation and reasoning scores were negatively correlated with the PANSS (r ranged from -0.27 to -0.33), and the negative subscale score (r ranged from -0.31 to -0.37) as well as positively correlated with the MMSE (r ranged from 0.26 to 0.43). All pvalues were less than 0.01. The factor analysis explained 57.6 % of the total variance; specifically, Components 1 and 2 contributed 44.5% and 13.1 % of the variance respectively. These findings indicate that the Chinese version of the MacCAT-CR is a reliable and valid instrument to assess the decision-making capacity to consent to clinical research of patients with schizophrenia spectrum disorders.

Do atypical antipsychotics really enhance smoking reduction more than typical ones?: the effects of antipsychotics on smoking reduction in patients with schizophrenia.

Whether atypical antipsychotics (AAs) can enhance smoking reduction in schizophrenic patients remains controversial because of methodological limitations in existing studies. This study explored whether certain types of antipsychotics predict smoking reduction in schizophrenic patients. Three hundred eight smoking, predominantly male schizophrenic patients (271/308 [88.9%]) participated in an 8-week open-label study with antismoking medications (high-dose, low-dose nicotine transdermal patch and bupropion). Antipsychotics were classified into (1) typical antipsychotics (TAs) and (2) AAs, including multiacting receptor-targeted antipsychotics (clozapine, olanzapine, and quetiapine), serotonin-dopamine antagonists (risperidone), D2/D3 receptor antagonists (amisulpride), and partial dopamine receptor agonists (aripiprazole). A general linear model was used to explore whether types of antipsychotic predict changes in the number of cigarettes smoked per day (CPD) and the score of the Fagerstrom Test for Nicotine Dependence (FTND) while controlling for confounding factors. The type of antipsychotic (TAs or AAs) was not significantly associated with smoking cessation (n = 21; χ = 1.8; df = 4; P = 0.77). Regarding smoking reduction, the type of antipsychotic was significantly predictive of a change in the CPD (P = 0.027; partial eta square = 0.055) and FTND scores (P = 0.002; partial eta square = 0.073). The 95% confidence intervals of the estimated means of change in the CPD and FTND scores did not contain zero only among subjects on TAs or clozapine.These findings suggest that TAs and clozapine enhance smoking reduction compared with nonclozapine atypical antipsychotics in schizophrenic patients. The mechanisms underlying the effects of various antipsychotics on smoking reduction remain unclear and warrant future study.

A double-blind randomized clinical trial of different doses of transdermal nicotine patch for smoking reduction and cessation in long-term hospitalized schizophrenic patients.

There have been many studies of smoking cessation using nicotine replacement therapy (NRT) with schizophrenic patients, but none exploring the smoking-reduction effects of varying doses of NRT in long-stay patients with schizophrenia. This study aimed to examine the effect of different doses of the nicotine transdermal patch on smoking-reduction and cessation outcomes in long-term hospitalized schizophrenic patients. A total of 184 subjects participated in a randomized, controlled, double-blind 8-week clinical trial. Participants were randomized into two groups using two different doses of NRT: a high-dose NRT group (31.2 mg for the first 4 weeks, then 20.8 mg for 4 weeks, n = 92) or a low-dose NRT group (20.8 mg for 8 weeks, n = 92). The 7-day point prevalence of abstinence was 2.7 % (5/184). Participants in the low-dose NRT group reduced smoking by 3.1 more cigarettes on average than those in the high-dose group (p = 0.005). However, a repeated measures analysis of variance revealed that the main effect of changes in the number of cigarettes smoked, comparing the two types of treatment across periods, was not significant (p = 0.35, partial eta square = 0.018). In summary, among a cohort of chronic institutionalized schizophrenic patients, smoking cessation and reduction outcomes were not correlated with NRT dose, and the cessation rate was much lower than rates in similar studies. It indicates that long-term hospitalized schizophrenic patients have more difficulties with quitting smoking. More effective integrative smoking cessation programs should be addressed for these patients.

Association of promoter variants of human dopamine transporter gene with schizophrenia in Han Chinese.

OBJECTIVE: Although dopamine was implicated in the etiology of schizophrenia, the human dopamine transporter gene (DAT1; SLC6A3) has not consistently been associated with schizophrenia. The purpose of this study was to examine whether six polymorphisms within the DAT1 gene are associated with schizophrenia. METHODS: Six polymorphisms of the DAT1 gene (3 SNPs [rs6413429, rs2652511, and rs2975226] in the promoter region, one SNP [rs6347] in exon 9, and one SNP [rs27072]/one variable number tandem repeat [VNTR] in exon 15) were analyzed in 352 Chinese patients with schizophrenia and in 311 healthy controls. Pretreatment psychopathology was assessed using the Positive and Negative Syndrome Scale in a subset of 160 hospitalized schizophrenia patients who were drug-free or drug-naïve. RESULTS: A statistically significant difference in two polymorphisms (rs2652511 and rs2975226) and a promoter region haplotype (rs2652511, rs2975226, and rs6413429) was found between patients and healthy controls. No association with schizophrenia was found for other polymorphisms and another haplotype (3' region). Symptoms severity (PANSS global, positive, negative and general symptoms scores) was similar regardless of DAT1 polymorphism. CONCLUSION: The promoter region of the DAT1 gene may play a role in increasing susceptibility to schizophrenia, but does not affect the severity of psychotic symptoms in Han Chinese.

Adjunctive use of methylphenidate in the treatment of psychotic unipolar depression.

Adjunctive use of methylphenidate, a central stimulant, has been considered as a potential therapeutic choice for patients with refractory unipolar depression, geriatric depression, bipolar depression, and depression secondary to a medical illness. We present a case of psychotic unipolar depression in which the patient responded significantly to the adjunctive use of methylphenidate. A 45-year-old woman had melancholic depressive symptoms and mood incongruent psychotic features during her second episode of unipolar depression. She attempted suicide by hanging herself and was forcibly hospitalized. She was initially treated with venlafaxine (262.5 mg/d), olanzapine (20 mg/d), and benzodiazepines. However, she responded unsatisfactorily to the combination treatment. Because her family refused electroconvulsive treatment, we added methylphenidate to her medications for adjunctive use. The dose of methylphenidate was started at a dose of 5 mg/d. It was not until the patient received 30 mg/d of methylphenidate that her persistent psychosis and severe depression were substantially improved. She tolerated her medications well and did not report any side effects. She was discharged in a stable condition 2 weeks after the adjunctive use of methylphenidate. The patient's methylphenidate was gradually tapered and finally discontinued. To date, she remains well and is regularly followed up at our outpatient clinic. Our case suggests that adjunctive use of methylphenidate can be a therapeutic option in treating some patients with psychotic unipolar depression who do not adequately respond to the combination treatment of an antidepressant and an atypical antipsychotic. Further controlled studies are warranted to verify this.

Ziprasidone in the treatment of delayed carbon monoxide encephalopathy.

Delayed carbon monoxide (CO) encephalopathy is a serious complication of acute CO poisoning. We present a case of successful treatment of ziprasidone, a newer atypical antipsychotic, in delayed CO encephalopathy. A 52-year-old depressed woman suffered acute CO intoxication after an attempt of suicide by burning charcoal. She was initially treated with hyperbaric oxygen (HBO) therapy for the acute intoxication. One week later, the patient developed neuropsychiatric symptoms including parkinsonism, tardive dyskinesia (TD), cognitive deterioration, urinary incontinence, gait disturbance, mutism, disorientation to time, place and person, and disorganized as well as disturbing behavior. During her psychiatric hospitalization, the patient had been treated with daily HBO therapy, bromocriptine (2.5 mg/day), the conventional antipsychotic sulpiride (600 mg/day), and atypical antipsychotics such as risperidone (5 mg/day) and quetiapine (400 mg/day). However, her delayed neuropsychiatric sequelae of CO intoxication persisted despite of these treatments. It was until she had been treated with ziprasidone (80 mg/day) for 10 days that her mental condition was improved. With ziprasidone therapy, the patient obtained substantial improvement in her neuropsychiatric symptoms, cognitive function, and daily activities. Our case indicates that ziprasidone can be used effectively in the treatment of delayed CO encephalopathy.