Defecation status, intestinal microbiota, and habitual diet are associated with the fecal bile acid composition: a cross-sectional study in community-dwelling young participants.

PURPOSE: Bile acid (BA) metabolism by intestinal bacteria is associated with the risk of gastrointestinal diseases; additionally, its control has become a modern strategy for treating metabolic diseases. This cross-sectional study investigated the influence of defecation status, intestinal microbiota, and habitual diet on fecal BA composition in 67 community-dwelling young participants. METHODS: Feces were collected for intestinal microbiota and BA analyses; data about defecation status and dietary habits were collected using the Bristol stool form scales and a brief-type self-administered diet history questionnaire, respectively. The participants were categorized into four clusters based on their fecal BA composition, according to cluster analysis, and tertiles based on deoxycholic acid (DCA) and lithocholic acid (LCA) levels. RESULTS: The high primary BA (priBA) cluster with high fecal cholic acid (CA) and chenodeoxycholic acid (CDCA) levels had the highest frequency of normal feces, whereas the second BA (secBA) cluster with high levels of fecal DCA and LCA had the lowest. Alternately, the high-priBA cluster had a distinct intestinal microbiota, with higher Clostridium subcluster XIVa and lower Clostridium cluster IV and Bacteroides. The low-secBA cluster with low fecal DCA and LCA levels had the lowest animal fat intake. Nevertheless, the insoluble fiber intake of the high-priBA cluster was significantly higher than that of the high-secBA cluster. CONCLUSION: High fecal CA and CDCA levels were associated with distinct intestinal microbiota. Conversely, high levels of cytotoxic DCA and LCA were associated with increased animal fat intake and decreased frequency of normal feces and insoluble fiber intake. CLINICAL TRIAL REGISTRY: University Hospital Medical Information Network (UMIN) Center system (UMIN000045639); date of registration: 15/11/2019.

Associations between the number of antipsychotics prescribed and metabolic parameters in Japanese patients with schizophrenia.

Aim: There is little evidence on the effects of antipsychotic polypharmacy on metabolic parameters in patients with schizophrenia. Thus, this cross-sectional study explored the associations between the number of antipsychotics prescribed and metabolic parameters in Japanese patients with schizophrenia. Methods: We obtained metabolic parameter data from 19,675 patients with schizophrenia. Of these, 1380 (7.0%), 8422 (42.8%), 6326 (32.2%), and 3547 (18.0%) were treated with none, one, two, and three or more antipsychotics, respectively. We compared eight metabolic parameters among the four groups using univariate analyses. We then performed multiple regression analysis to assess the effect of the number of antipsychotics prescribed on metabolic parameters after controlling for the effects of age, sex, type of care (outpatient/inpatient), chlorpromazine-equivalent dose, and antipsychotic type (aripiprazole, olanzapine, and risperidone). Results: There were significant differences in body mass index (BMI), systolic and diastolic blood pressure (dBP), total cholesterol, low-density lipoprotein cholesterol, and triglycerides among the four groups. The multiple regression analysis showed that the number of antipsychotics prescribed was significantly correlated with BMI and dBP (standardized regression coefficient = 0.031 and 0.026, respectively). Conclusion: Our results suggested that the number of antipsychotics prescribed adversely affects BMI and dBP. Clinicians should avoid inappropriate antipsychotic polypharmacy, especially polypharmacy involving three or more antipsychotics.

Predictive Utility of Body Mass Index for Metabolic Syndrome Among Patients with Schizophrenia in Japan.

BACKGROUND: Reliable and easy screening for metabolic syndrome (MetS) is important for patients with schizophrenia. The aim of this study was to assess the predictive utility of body mass index (BMI) for MetS among patients with schizophrenia in Japan. METHODS: In total, 8468 patients (4705 males, 3763 females) with schizophrenia or schizoaffective disorders based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), or the International Classification of Diseases, tenth revision (ICD-10), were assessed for MetS using the criteria of the National Cholesterol Education Program Adult Treatment Panel III (ATP III-A). We applied a stratum-specific likelihood ratio (SSLR) analysis, which is independent of the prevalence of the target disease. RESULTS: The mean (± standard deviation) age of these patients was 57.4 ± 13.5 years. The prevalence of MetS was 20.4%. Among males, the SSLRs predicting MetS were 0.03 (95% CI 0.02-0.06), 0.54 (95% CI 0.48-0.60), 2.77 (95% CI 2.44-3.14) and 8.75 (95% CI 7.40-10.36) for BMI <20 kg/m2, 20 kg/m2 ≤ BMI < 25 kg/m2, 25 kg/m2≤ BMI < 28 kg/m2, and 28 kg/m2≤BMI, respectively. For females, the SSLRs predicting MetS were 0.08 (95% CI 0.05-0.12), 0.73 (95% CI 0.66-0.82), 2.50 (95% CI 2.16-2.90) and 4.83 (95% CI 4.12-5.67) for the same BMI categories, respectively. CONCLUSION: The predictive utility of BMI is confirmed, and BMI has more predictive value in males than in females. Patients with a BMI of 28 kg/m2 or greater had a significantly higher SSLR than those with a BMI less than 28 kg/m2.

Lower Prolactin Levels in Patients Treated With Aripiprazole Regardless of Antipsychotic Monopharmacy or Polypharmacy.

BACKGROUND: Hyperprolactinemia is a troublesome adverse effect of antipsychotics. Aripiprazole (ARP), which is one of second-generation antipsychotics, has been reported to lower serum prolactin (PRL) levels. However, few studies have compared the effect of ARP on plasma PRL levels between monopharmacy and polypharmacy with antipsychotics. METHODS: We conducted a large-scale investigation of the physical risk for inpatients with schizophrenia using a questionnaire covering demographic data, the number, dose and type of antipsychotics, and serum PRL levels. RESULTS: Sufficient data to conduct an assessment of the effect on PRL levels between antipsychotic monopharmacy and polypharmacy were obtained from 316 of the inpatients. Serum PRL levels in ARP combination group were lower than non-ARP combination group, regardless of antipsychotic monopharmacy or polypharmacy. CONCLUSIONS: The present study suggests that ARP lowers serum PRL levels regardless of monopharamacy or polypharmacy with antipsychotics.

High-density lipoprotein-cholesterol and antipsychotic medication in overweight inpatients with schizophrenia: post-hoc analysis of a Japanese nationwide survey.

BACKGROUND: Patients with schizophrenia have an increased prevalence of metabolic disturbances compared with the general population. However, the mechanisms underlying the metabolic side effects of antipsychotics are unknown. The aim of the present study was to compare the levels of high-density lipoprotein (HDL)-cholesterol in Japanese schizophrenia patients medicated with olanzapine, risperidone, or aripiprazole monotherapy. METHODS: This study was a post-hoc analysis of a nationwide survey, which included 433 Japanese outpatients with schizophrenia and 674 inpatients. A brief questionnaire was compiled that covered demographic data, systolic blood pressure, diastolic blood pressure, and HDL-cholesterol after reviewing the relevant literature and guidelines. To compare demographic and clinical characteristics, analysis of variance was performed for continuous variables and the chi-square test was performed for categorical variables. For comparisons of HDL-cholesterol levels among the three antipsychotic groups, analysis of covariance was carried out with age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference as confounding variables after stratification by body mass index (BMI) for each outpatient group and inpatient group. RESULTS: The mean age was 57.9 ± 14.0 years and the mean BMI was 23.4 ± 4.5 kg/m2. HDL-cholesterol levels when stratified by BMI differed significantly (p = 0.019) between the three antipsychotic groups after age, diastolic blood pressure, chlorpromazine-equivalent dosage, and waist circumference in inpatients. A significant difference in HDL-cholesterol levels was only found in the overweight inpatient group, and no significant differences in HDL-cholesterol levels were found among the three antipsychotics for outpatients of all BMI stratifications or inpatients that were underweight or of normal weight. For post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group (p = 0.023). CONCLUSIONS: This study reveals a difference in HDL-cholesterol levels in overweight Japanese inpatients with schizophrenia resulting from the use of different antipsychotics. In the post-hoc analysis of HDL-cholesterol levels in overweight inpatients, HDL-cholesterol was significantly lower in the olanzapine group than in the aripiprazole group. Further studies incorporating more detailed evaluations, including diet and physical activity, are needed to clarify the differences in HDL-cholesterol according to antipsychotic use.

Effects of nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan: A randomized controlled trial.

OBJECTIVE: Patients with schizophrenia have a higher prevalence of metabolic syndrome (MetS) than the general population. Minimizing weight gain and metabolic abnormalities in a population with an already high prevalence of obesity is of clinical and social importance. This randomized controlled trial investigated the effect of monthly nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan. METHODS: From July 2014 to December 2014, we recruited 265 obese patients who had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Participants were randomly assigned to a standard care (A), doctor's weight loss advice (B), or an individual nutritional education group (C) for 12 months. The prevalence of MetS and body weight were measured at baseline and 12 months. RESULTS: After the 12-month treatment, 189 patients were evaluated, and the prevalence of MetS based on the ATP III-A definition in groups A, B, and C was 68.9%, 67.2%, and 47.5%, respectively. Group C showed increased weight loss (3.2 ± 4.5 kg) over the 12-month study period, and the change in weight differed significantly from that of group A; additionally, 26.2% of the participants in group C lost 7% or more of their initial weight, compared with 8.2% of those in group A. CONCLUSION: Individual nutrition education provided by a dietitian was highly successful in reducing obesity in patients with schizophrenia and could be the first choice to address both weight gain and metabolic abnormalities induced by antipsychotic medications.

High Prevalence of Obesity, Hypertension, Hyperlipidemia, and Diabetes Mellitus in Japanese Outpatients with Schizophrenia: A Nationwide Survey.

BACKGROUND: Patients with schizophrenia have significantly shorter life expectancy than the general population, and a problem they commonly face is an unhealthy lifestyle, which can lead to obesity and metabolic syndrome. There is a very clear need to determine the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus which are components of metabolic syndrome in patients with schizophrenia, but there has been a paucity of large-scale studies examining this situation in Japan. The aim of our study was to address this need. SETTING & PARTICIPANTS: We conducted a large-scale investigation of the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus using a questionnaire in 520 outpatient facilities and 247 inpatient facilities of the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7,655 outpatients and 15,461 inpatients with schizophrenia. RESULTS: The outpatients had significantly higher prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus than the inpatients. The prevalence of hypo-HDL cholesterolemia was higher in inpatients than outpatients. Age-specific analysis showed the prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus among outpatients to be 2- to 3-fold higher than among inpatients. In individuals aged ≥60 years, the prevalence of obesity and DM among outpatients was about 3-fold higher than among inpatients. CONCLUSION: Japanese outpatients with schizophrenia were more likely to have physical risk such as obesity, hypertension, hyperlipidemia, and diabetes mellitus than inpatients. The physical risk to patients with schizophrenia may be affected by environmental parameters, such as type of care. The physical risk to Japanese patients with schizophrenia demands greater attention.

Attitudes toward metabolic adverse events among patients with schizophrenia in Japan.

BACKGROUND: Metabolic syndrome is a growing concern among patients with schizophrenia because metabolic abnormalities are widely regarded as a major risk factor for cardiovascular disease and premature death. The current study assessed attitudes toward metabolic adverse events among patients with schizophrenia. METHODS: A brief questionnaire was constructed to investigate patient recognition of the following broad areas: dietary habits, lifestyle, self-monitoring, knowledge, and medical practice. Between January 2012 and June 2013, questionnaires were sent to patients associated with 520 outpatient facilities and 247 inpatient facilities belonging to the Japan Psychiatric Hospital Association. All of the participants (n=22,072; inpatients =15,170, outpatients =6,902) were diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, or the International Classification of Diseases, tenth revision. RESULTS: Approximately 55.0% (8,069/14,669) of inpatients and 44.8% of outpatients (2,978/6,649) reported that they did not exercise at all. Although 60.9% (4,116/6,760) of outpatients reported that they felt obese, only 35.6% (5,261/14,794) of inpatients felt obese. More than half of the inpatients (51.2%; 7,514/14,690) and outpatients (60.8%; 4,086/6,721) hoped to receive regular blood tests to prevent weight gain and diseases such as diabetes. CONCLUSION: Although more than half of patients hoped to prevent weight gain and diabetes, only a minority of patients were mindful of eating balanced meals and having physical exercise. Educational efforts and the promotion of the best pharmacotherapy and monitoring practices are needed for patients with schizophrenia.

Difference in prevalence of metabolic syndrome between Japanese outpatients and inpatients with schizophrenia: A nationwide survey.

Patients with schizophrenia have a higher risk of metabolic syndrome (MetS). MetS prevalence varies with ethnicity. Although environmental factors, such as lack of physical activity and unbalanced diet, can lead to MetS, these may differ between outpatients and inpatients with schizophrenia. The Japanese mental health care system differs from that in other countries. However, few studies have investigated the prevalence of MetS in Japanese patients with schizophrenia. Therefore, we conducted a nationwide survey to clarify the prevalence of MetS in Japanese outpatients and inpatients with schizophrenia. We investigated the risk of MetS by questionnaire in 520 facilities for outpatients and 247 facilities for inpatients. There were 7655 outpatients and 15,461 inpatients with schizophrenia. MetS prevalence was based on the National Cholesterol Education Program Adult Treatment Panel III (ATP III-A) and the Japan Society for the Study of Obesity (JASSO). The overall MetS prevalence in outpatients using the ATP III-A definition was 34.2%, with 37.8% in men and 29.4% in women, compared with 13.0% in inpatients, with 12.3% in men and 13.9% in women. MetS prevalence in outpatients was approximately 2- to 3-fold higher than in inpatients. In conclusion, MetS prevalence in Japanese outpatients was approximately 3-fold higher than in inpatients. Therefore, we should pay more attention to the risk of physical disease in Japanese patients with schizophrenia, considering the difference in health characteristics between outpatients and inpatients.

High prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia: a nationwide survey.

OBJECTIVES: To clarify the prevalence of underweight and overweight/obesity, and laboratory data for nutritional status in Japanese outpatients and inpatients with schizophrenia. DESIGN: Cross-sectional study. SETTING: A questionnaire conducted in inpatient and outpatient facilities in Japan. PARTICIPANTS: The population of adult patients with schizophrenia in Japan (N=23,116). MAIN OUTCOME MEASURES: The prevalence of underweight and undernutrition in Japanese inpatients and outpatients with schizophrenia. RESULTS: We conducted a large-scale investigation of the prevalence of underweight and undernutrition in 520 outpatient facilities and 247 inpatient facilities belonging to the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7655 outpatients and 15,461 inpatients with schizophrenia. There was a significant difference in the distribution of three body mass index levels between outpatients and inpatients (p<0.001). The proportion of underweight inpatients with schizophrenia was significantly higher than that among outpatients (p<0.001). Age-specific analysis revealed that the proportion of underweight individuals aged ≥ 40 years was higher in inpatients than in outpatients and in the general Japanese population. The proportion of individuals with hypocholesterolaemia was significantly higher in inpatients with schizophrenia than in outpatients (p<0.001). There was a significant difference in the severity of underweight between outpatients and inpatients with schizophrenia; the proportion of severe underweight in inpatients was twofold higher than in outpatients. CONCLUSIONS: The prevalence of underweight and undernutrition in Japanese inpatients with schizophrenia was higher than in outpatients and the general population. Therefore, the physical risk of inpatients should be carefully considered in clinical practice.

[Survey of obesity and underweight among inpatients with schizophrenia in psychiatric hospitals throughout Japan].

AIM: Many studies have reported a high prevalence of obesity in patients with schizophrenia compared to the general population. However, no nationwide survey of schizophrenic inpatients has been conducted in Japan. The aims of this study were to conduct a large-scale survey of BMI among hospitalized patients with schizophrenia in Japan, identify the prevalence of obesity and underweight, and examine its associated factors. METHODS: This was a cross-sectional study. The subjects were 14,591 schizophrenic inpatients (7,645 males and 6,946 females) with complete data from 89 facilities in Japan that agreed to participate in this study. Survey items included age, gender, height, weight, BMI, length of hospital stay, antipsychotic agents, and types of hospital ward, and the survey took place between July to December 2010. RESULTS: When the BMI distribution was compared between the general adult population and patients, the rate of obesity was 26.1% in the general adult population and 21.9% in the patients, being lower among the patients, and the rate of underweight was 7.0% in the general adult population and 19.5% in the patients, being 2.8 times higher among the patients. Subsequently, logistic regression was used to examine factors associated with obesity and underweight. As the results, the obesity odds ratio was 1.32 times higher in patients in their 30s than in their 20s, 1.31 times higher in females than males, 0.62 times higher with a > or = 1-year hospital stay than < 3-month stay, 1.42 times higher in patients receiving > or = 4 antipsychotic agents than those receiving single typical agents, and 0.58 times higher in patients kept in a locked ward than those in an open ward. The underweight odds ratio was 2.03 times higher in patients in their > or = 70s than in their 20s, 1.18 times higher in females than males, 1.47 times higher with a 3-month < 1-year hospital stay than < 3-month stay, 0.7 times higher in patients receiving > or = 4 antipsychotic agents than those receiving single typical or atypical agents, and 1.81 times higher in patients kept in a locked ward than those in an open ward. CONCLUSIONS: Obesity in Japanese schizophrenic inpatients was associated with < 3-month hospitalization, antipsychotic polypharmacy, and an open ward, whereas underweight was associated with > or = 3-month hospitalization, the administration of single typical or atypical antipsychotic agents, and a locked ward, independent from age and gender.

Body mass index of inpatients with schizophrenia in Japan.

OBJECTIVE: Many studies reported that obesity rate in the Western countries is higher in schizophrenia patients than in general population. In this study, we surveyed nationwide Body Mass Index (BMI) status of hospitalized Japanese schizophrenia patients. METHODS: Subjects included 15,171 patients (7,897 men and 7,274 women) hospitalized for schizophrenia, who were sampled from all 47 administrative divisions in Japan. The BMI data of these patients were compared to those of the general population in the 2009 National Health and Nutrition Survey conducted by the Japanese Ministry of Health. RESULTS: The median BMI value in the patients was 21.6 kg/m2 (first quartile, 19.1; third quartile, 24.5). The percentages of BMI in obese, normal-weight, and underweight patients were 21.6%, 58.2%, and 20.2%, respectively. In the Japanese male patients, frequency of obesity was lower, and underweight was higher than those in the general population. In female patients, frequency of both obesity and underweight were higher than those in the general population. CONCLUSIONS: Our results provided evidence that underweight as well as obesity is a characteristic in Japanese schizophrenia inpatients.