A cross-sectional study on metabolic similarities and differences between inpatients with schizophrenia and those with mood disorders.

BACKGROUND: One of the main causes of death in psychiatric patients is cardiovascular diseases which are closely related with lifestyle-related diseases. Psychiatric disorders include schizophrenia and mood disorders, whose symptoms and treatment medicines are different, suggesting that they might have different metabolic disorders. Thus, we studied the differences of lifestyle-related diseases between schizophrenia and mood disorders in Japan. METHODS: This cross-sectional study was performed from 2015 to 2017. Study participants were 189 Japanese hospitalized patients (144 schizophrenia group, 45 mood disorders group) in the department of psychiatry at Kohnodai hospital. We examined physical disorders, metabolic status of glucose and lipid, estimated glomerular filtration rate (eGFR) and brain magnetic resonance imaging. We compared these data between schizophrenia and mood disorders groups using analysis of covariance or logistic regression analysis. In comparisons between inpatients with schizophrenia or mood disorders group and the standard, we quoted 'The National Health and Nutrition Survey in Japan 2015' by Ministry of Health, Labor and Welfare as the standard. RESULTS: eGFR and prevalence of smoking were significantly lower in patients with mood disorder group than those with schizophrenia group by adjustment for age. In comparisons between patients with schizophrenia group or mood disorders group and each standard, the ratio of silent brain infarction (SBI) and cerebral infarction were significantly high in both groups. Schizophrenia group showed significantly higher prevalence of diabetes, low high-density lipoprotein (HDL) cholesterolemia, metabolic syndrome and smoking than the standard. Mood disorders group had significantly high prevalence of low HDL-cholesterolemia compared with the standard. Fasting blood glucose and HbA1c were significantly higher in schizophrenia group and female mood disorders group than the standard. Female mood disorders group had significantly decreased eGFR with increased ratio of eGFR < 60 ml/min than the standard. CONCLUSIONS: Participants of both groups had increased ratio of SBI and cerebral infarction, accompanied with glucose and lipid disorders. Compared with schizophrenia group, mood disorders group showed significantly low eGFR and prevalence of smoking.

[Clinical experience with clozapine in 55 cases of treatment-resistant schizophrenia].

Up until October 2012, Kohnodai Hospital had introduced clozapine treatment for 55 cases of treatment-resistant schizophrenia. In all cases, previous antipsychotic medication was discontinued the day before clozapine administration began. Of the 55 cases, 45(85%)are continuing clozapine administration, and 40 cases (73%) are receiving outpatient treatment. The average dose of clozapine was 373.1 mg/day (SD : 160.5). Clozapine was administered for a month or more in 51 cases (93%). BPRS scores improved 20% or more in a month's administration of clozapine in 18 of the cases (35%). The average clozapine dose in the improvement cases was 176 mg/day. The average BPRS score had significantly decreased from the baseline at months 1, 3, 6, and 12 after the start of clozapine administration. Of the 33 cases receiving clozapine treatment for 12 months or more, BPRS improved 20% or more in 27 (82%). BPRS improved 20% or more for the first time after clozapine administration within a month in 12 cases (44%), 3 months in 8 cases (30%), 6 months in 5 cases (19%), and 12 months in 2 cases (7%). These results suggest that clozapine should be administered continuously for over 6 months at the least and 12 months if possible to evaluate the efficacy of clozapine treatment. Of the 43 cases receiving outpatient clozapine therapy, the average GAF score improved significantly from the time of ward admission to discharge (20.6 and 42.0, respectively). Clozapine had to be discontinued in 2 cases of leukopenia, 2 cases of neutropenia, 1 case of reduced left ventricular ejection due to pericardial effusion, 1 case of drug eruption, and 1 case of marked hunger. When introducing clozapine for treatment-resistant schizophrenia, it is important to administer it as a monotherapy, slowly increase the dosage to reduce side effects, and achieve a treatment effect at the minimum required dosage.

Comparison of severe hyponatremia in patients with and without psychiatric diseases: A single-center retrospective study.

Aims: Hyponatremia is a common electrolyte disorder. The severe hyponatremia has a mortality rate of 4%-40%. Psychiatric patients are likely to develop the condition because of polydipsia or the adverse effects of antipsychotics. We investigated the characteristics of patients with and without psychiatric diseases who developed severe hyponatremia. Materials and Methods: We retrospectively investigated cases admitted to our hospital (all departments) between October 2012 and November 2015 with a serum sodium concentration of ≤125 mmol/l on admission. We compared patient characteristics, etiology, and clinical course between psychiatric and nonpsychiatric patients. Results: In total, 123 cases (62 female) were analyzed. Psychiatric disorders were present in 69 cases (56%), including schizophrenia (n = 19), anorexia (n = 16), mood disorders (n = 14), and organic mental disorders (n = 9). The mean patient age was 63 years. The mean serum sodium concentration on admission was 119 mmol/l, and the main causes of hyponatremia were polydipsia (20%), insufficient sodium intake (18%), and syndrome of inappropriate antidiuretic hormone secretion (16%). Compared with the nonpsychiatric group, the psychiatric group was significantly younger (55 vs. 74 years), was more likely to have polydipsia (30% vs. 6%), and had a lower in-hospital mortality (0% vs. 17%). Conclusions: Our study found differences in the clinical picture between psychiatric and nonpsychiatric patients with severe hyponatremia. Clinicians need to monitor serum sodium because the symptoms of hyponatremia can mimic those of psychiatric diseases.

Establishment of a new murine model of hypercalcemia with anorexia by overexpression of soluble receptor activator of NF-κB ligand using an adenovirus vector.

Hypercalcemia is a significant complication of certain human malignancies that is primarily caused by the release of calcium from bone due to marked bone resorption by osteoclast activation. Osteoclast differentiation and activation is mediated by receptor activator of NF-κB ligand (RANKL). Transgenic mice overexpressing murine soluble RANKL (sRANKL) that we generated previously exhibited severe osteoporosis accompanied with enhanced osteoclastogenesis, but never exhibited hypercalcemia. To analyze the relationship between serum concentration of sRANKL and hypercalcemia and generate a simple and quick hypercalcemia model, an adenovirus vector harboring murine sRANKL cDNA (Ad-sRANKL) was injected i.p. into male C57BL/6 mice. Sera were collected to measure the levels of sRANKL, calcium and biochemical markers of bone turnover. Food intake and body weight were measured every 3 or 4 days. All the mice were killed 2 weeks after the injection, and femurs were collected to measure bone structure and bone mineral density (BMD). Serum sRANKL and calcium increased, peaking on day 7. Food intake and body weight significantly declined on day 7. These results indicated that the mice had anorexia as a symptom of hypercalcemia. Increases in bone resorption and formation markers with a marked decrease in BMD were observed on day 14. These results reflect accelerated bone formation following activation of osteoclasts, indicating coupling between bone formation and resorption. In conclusion, a new murine model of hypercalcemia with anorexia was established by overexpressing sRANKL. This model would be useful for studies of hypercalcemia and coupling between bone formation and resorption.

Metabolic changes of Japanese schizophrenic patients transferred from hospitalization to outpatients.

It is well known that schizophrenic patients have high incidence of metabolic syndrome and life-style related diseases. There are reports that the rates of these diseases are increased more in outpatients than inpatients, but are also reports that the rates are not different between both patient groups. These differences might be related to the length of hospitalization. Hospitalization of Japanese psychiatric patients is about 300 days, much longer than western countries (below 50 days). Therefore, we investigated lipid and glucose metabolism of schizophrenic patients transferred from hospitalization to outpatients at Kohnodai hospital with a mean of 80 days hospitalization period to clarify metabolic characteristics in Japanese patients. Study participants were 144 schizophrenia inpatients and 109 outpatients at Kohnodai Hospital. These 109 outpatients were followed for approximately 2 years, without changes of administrated drugs, and from 144 inpatients. Data from outpatients were obtained at 6 months, 1 year and 2 years after their discharge. Outpatients 2 years after discharge had significantly higher levels of total cholesterol, triglyceride and non-high density lipoprotein (non-HDL) cholesterol than inpatients, accompanied with an increase of body weight. Serum HDL-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels had no significant difference between both groups. These lipids and glucose levels also showed the same tendency in outpatients 0.5 year and 1 year after discharge as those after 2 years. We found that schizophrenic patients in our study appeared to have changes of lipid metabolism 2 years after their discharge, but no significant changes of glucose metabolism, such as FPG and HbA1c.

Development of diabetes mellitus associated with quetiapine: A case series.

We aimed to describe the characteristics and clinical course of patients who developed diabetes associated with the use of quetiapine.This study included patients who received quetiapine for over a month between April 2008 and November 2013, and were diagnosed as having new-onset diabetes after initiation of quetiapine. We excluded patients who developed diabetes more than 1 year after discontinuation of quetiapine. We identified new-onset diabetes by hemoglobin A1c or prescriptions of antidiabetic drugs.Among 1688 patients who received quetiapine, hemoglobin A1c had been measured in 595 (35.2%) patients at least once during the observation period, and 33 (2.0%) patients had received hypoglycemic drugs. Eighteen (1.1%) patients were considered to have developed new-onset diabetes associated with quetiapine after a median of 1.6 years following initiation of quetiapine. Median (interquartile range) age was 54.5 (29.8) years, 8 patients were male, and median (interquartile range) duration of mental illness was 15.3 (13.8) years. Median hemoglobin A1c and body mass index (BMI) were 7.1 (1.4) % and 28.4 (7.0) kg/m, respectively. Seventeen patients had dyslipidemia when diabetes was discovered. All of these discontinued quetiapine within 3 months after the diagnosis of diabetes, and the diabetes in 4 patients had ameliorated without hypoglycemic drugs. Of 13 patients who had received either oral hypoglycemic drugs or insulin, 2 patients achieved well-controlled hemoglobin A1c without hypoglycemic drugs, and 10 patients had hemoglobin A1c 5.0% to 7.7% with the continued use of hypoglycemic drugs.We demonstrated that almost all patients who developed quetiapine-associated diabetes had dyslipidemia and increased BMI. There was no life-threatening hyperglycemia and diabetes was ameliorated just by discontinuation of quetiapine in several patients. The monitoring of metabolic parameters during antipsychotic treatment is important to diagnose and treat diabetes earlier.