Multi-regression analysis revealed a relationship between l-serine and methionine, a component of one-carbon metabolism, in the normal control but not in the schizophrenia.

BACKGROUND: Alterations in one-carbon metabolism (OCM) have been observed in patients with schizophrenia (SZ), but a comprehensive study of OCM has not yet been conducted. A carbon atom is transferred from l-serine to methionine during OCM, but the relationship between l-serine and methionine in SZ is not yet known. We investigated the relationship between l-serine and methionine to obtain a comprehensive understanding of OCM in SZ. METHODS: We recruited forty-five patients with SZ and thirty normal controls (NC). Whole blood, plasma, and DNA specimens were obtained from all participants. Plasma l-serine, d-serine, glycine, methionine, and total homocysteine levels were measured using high-performance liquid chromatography. Plasma vitamin B12 and total folate were measured using a chemiluminescent protein-binding immunoassay. Clinical symptoms were estimated using the positive and negative syndrome scale (PANSS). The methylenetetrahydrofolate reductase (MTHFR) C667T genotype and A298C genotype, which are involved in MTHFR activity, were determined using the TaqMan genotyping assay system. RESULTS: Analysis of variance was used to confirm that the SZ cohort has higher plasma homocysteine levels and lower plasma folate levels than the NC group. Multi-regression analysis revealed a relationship between l-serine and methionine in the NC group but not in the SZ group. The MTHFR genotype did not affect the relationship between l-serine and methionine in each group. The total PANSS score was significantly related to d-serine and folate levels and to age. Positive PANSS scores were significantly related to both glycine and sex. In addition, both glycine and d-serine were significantly correlated with negative PANSS scores. CONCLUSIONS: We found impairment of the relationship between l-serine and methionine in SZ. Clinical symptoms of SZ were partially correlated with the OCM components. These findings contributed to our understanding of OCM alteration in SZ and may explain why the alteration occurs.

Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report.

BACKGROUND: Cases of acute pancreatitis caused by sodium valproate (VPA) have been reported by many authors thus far. However, most of these were cases with epilepsy. Chronic renal failure is also regarded as a risk factor for acute pancreatitis. Here, we report a case of acute pancreatitis development due to VPA in a patient with bipolar disorder on hemodialysis for chronic renal failure. CASE PRESENTATION: The patient was a 52-year-old Japanese male who was diagnosed as bipolar disorder on hemodialysis for renal failure. He was treated with VPA and manic symptoms gradually stabilized. However, the patient complained of severe abdominal pain. Blood amylase was found to be markedly high, and computed tomography revealed pancreatomegaly and an increased amount of peripancreatic fat. Hence, we diagnosed the case as acute pancreatitis caused by VPA. We discontinued oral medication, and he was started on a pancreatic enzyme inhibitor, antibiotics, and transfusion, and he showed improvement. CONCLUSION: It has been reported that acute pancreatitis induced by VPA is caused by intermediate metabolites of VPA. We consider that patients with renal failure are prone to pancreatitis caused by VPA because of the accumulation of these intermediate metabolites. We need close monitoring for serious adverse effects such as pancreatitis when we prescribe VPA to patients with bipolar disorder on hemodialysis for chronic renal failure, although VPA is safer than other mood stabilizers.

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period: Retrospective cohort study.

BACKGROUND: Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period. METHODS: We enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran-Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20-year period. RESULTS: Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20-year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20-year period. CONCLUSIONS: Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic-induced constipation.

Effect of antipsychotic use by patients with schizophrenia on deceleration capacity and its relation to the corrected QT interval.

OBJECTIVE: Schizophrenia patients treated with antipsychotics are at higher risk of sudden cardiac death. Decreased deceleration capacity (DC) of the heart rate is an accurate predictor of cardiac mortality. We evaluated the risk of sudden cardiac death due to antipsychotic use by assessing DC and examining the association between DC and the corrected QT interval (QTc) in schizophrenia patients. METHODS: We measured the DC and QTc of 138 schizophrenia patients. We then compared the DC of 86 age- and sex-matched healthy controls with that of 86 schizophrenia patients. We investigated the correlation of DC of approximately 138 schizophrenia patients with prescribed doses of antipsychotics using linear regression analysis. We compared the DC of schizophrenia patients with and without prolonged QT intervals. RESULTS: We found DC significantly differed between schizophrenia patients on antipsychotic medication and healthy controls. Additionally, DC was negatively correlated with antipsychotic use, especially chlorpromazine, zotepine, olanzapine and clozapine, in a dose-dependent manner. There was no significant association between DC and the QTc. CONCLUSION: Assessing DC could facilitate monitoring and identification of increased risk of cardiac mortality in patients with schizophrenia that take antipsychotics. Assessing both DC and the QTc may enhance the accuracy of predicting sudden cardiac death.

The relationship of stress coping styles on substance use, depressive symptoms, and personality traits of nurses in higher education institution.

AIM: This study examined the collective characteristics of nurses and their stress coping style. METHODS: We conducted a cluster analysis of the stress coping strategies of 841 nurses belonging to Dokkyo Medical University Hospital, as measured by the Brief COPE (Coping Orientation to Problems Experienced). We also conducted multivariate analyses of each cluster's sociodemographic characteristics, personality traits, depressive symptoms, work attitudes, sense of fairness, and turnover intention. RESULTS: The results of cluster analysis using the standardized z scores of the Brief COPE demonstrated that the study participants were classified into three clusters. The "emotional-response type" tended to favor the use of emotional support, venting, and self-blame. The "reality-escape type" tended to prefer alcohol and substance use, behavioral resignation, use of instrumental support, and lack of acceptance. The "problem-solving type" tended to prefer planning, positive reframing, and acceptance and to dislike "alcohol and substance use" and behavioral disengagement. A multinomial logistic regression analysis revealed that compared to the problem-solving type, the emotional-response type had a lower job title, a higher "neuroticism" score on the TIPI-J, and a higher K6 score. However, compared to the problem-solving type, the reality-escape type was younger, consumed more alcohol and substances, and had a higher K6 score. CONCLUSIONS: Stress coping styles were found to be associated with substance use, depressive symptoms, and personality traits among nurses in higher education institutions. Thus, the results suggest that nurses who choose maladaptive stress coping styles require mental support and early identification of depressive symptoms and alcohol problems.

Prescribing Trends for the Same Patients with Schizophrenia Over 20 Years.

Background: Recent pharmacoepidemiology data show an increase in the proportion of patients receiving second-generation antipsychotic (SGA) monotherapy, but no studies have analyzed the same patients over a long period of time. Therefore, in this study, we retrospectively evaluated schizophrenia patients with available data for 20 years to determine whether the drug treatments in the same patients have changed in the past 20 years. Methods: The study began in April 2021 and was conducted in 15 psychiatric hospitals in Japan. Schizophrenia patients treated in the same hospital for 20 years were retrospectively examined for all prescriptions in 2016, 2011, 2006, and 2001 (ie, every 5 years). Results: The mean age of the 716 patients surveyed in 2021 was 61.7 years, with 49.0% being female. The rate of antipsychotic monotherapy use showed a slight increasing trend over the past 20 years; the rate of SGA use showed a marked increasing trend from 28.9% to 70.3% over the past 20 years, while the rate of SGA monotherapy use showed a gradual increasing trend over the past 20 years. The rates of concomitant use of anticholinergics, antidepressants, anxiolytics/sleep medications, and mood stabilizers showed decreasing, flat, flat, and flat trends over the past 20 years, respectively. Conclusion: The results of this study showed a slow but steady substitution of SGAs for first-generation antipsychotics (FGAs) over time, even in the same patients.

Predictors of the intentions to leave among nurses in an academic medical center.

Aim: Nurses are an essential human resource for the healthcare system. However, high turnover of nurses is a current issue. Reducing the high turnover of nurses is crucial for facilitating the sustainable provision of care in hospitals. The purpose of this study was to explore the factors affecting nurses' intentions to leave among nurses in an advanced medical center. Methods: Using a cross-sectional design, we conducted a questionnaire survey of nurses working at an academic medical center in August 2020. Of the 1063 distributed questionnaires, there were 821 (77.2%) valid responses. The questionnaire included items on the Kessler 6 (K6), New Brief Job Stress Questionnaire (New BJSQ), Organizational Justice Questionnaire (OJQ), and intention to leave a hospital job. Results: Overall, the mean age of the nurses was 34.3 ± 10.1 years and 87.8% (721/821) of them were female. Among respondents, 19.5% (160/821) had a strong intention to leave. After adjusting for all the variables, a logistic regression analysis revealed that longer working hours, job rank (staff nurse), work-self-balance positive (imbalance), workplace harassment (no bullying), and interactional justice (unfair supervisor) were determinants associated with strong intentions to leave. Conclusions: Approximately one-fifth of nurses working at advanced medical center had a strong intention to leave. However, our findings can help managers predict the turnover of nurses by understanding occupational characteristics. Managing work-self-balance and treating staff fairly could improve work environments. Further research focusing on the outcome of actual turnover rather than intention to leave is needed.

Factors associated with the work-self balance of nurses in an advanced medical center.

Aim: Balancing between personal and working life of nurses is important to increase their job satisfaction and to continue their careers. Our purpose was to investigate the relationship between nurses and work-self balance (WSB) at different phases of life, such as age, marriage and raising children, and the occupational factors that influence WSB that can be used to improve the work environment for nurses. Methods: Using a self-administered questionnaire, we asked about gender, age, marital status, presence of children, working hours, and night shift. Occupational stresses, including WSB, were assessed with the New Brief Job Stress Questionnaire (New BJSQ) and the Organizational Justice Questionnaire (OJQ). The total number of unmarried and married respondents was 819. We investigated whether marital status and cohabiting children make a difference in WSB in the three age groups (less than 30 years, 31-40 years, and more than 41 years) using a Mann-Whitney U test. In addition, we examined occupational factors affecting WSB using multiple regression analysis. Results: The value of WSB negative was significantly greater in the group of married persons than in the group of unmarried persons (p < 0.05) and was significantly greater in the group with cohabiting children than in the group without cohabiting children (p < 0.01) only in the group aged 31-40 years. Multiple regression analysis indicated that significant occupational factors affecting WSB differed by each age group. Conclusion: This survey showed that the factors and degree of WSB vary according to the generation and family environment of nurses.

A pregnant woman who experienced auditory hallucinations concurrent with hyperemesis gravidarum: A case report.

We report the case of a pregnant woman who experienced auditory hallucinations only while suffering from hyperemesis gravidarum. To the best of our knowledge, the present report is the first report of a case of obvious auditory hallucinations and hyperemesis gravidarum at the same time in a pregnant woman who had not been diagnosed with any psychiatric disorder. The patient was a 24-year-old pregnant woman with no history of psychiatric disorder. Two years prior to this admission, she became pregnant for the first time, and she was admitted to an obstetrics clinic due to severe hyperemesis gravidarum. She developed mild auditory hallucinations at the same time. After she gave birth, the auditory hallucinations disappeared. When she was 24 years old, she became pregnant again. She suffered from severe hyperemesis gravidarum from the early stage of pregnancy. At 20 weeks of pregnancy, she visited the Department of Psychiatry of our hospital for a detailed psychiatric evaluation and treatment because her moderate auditory hallucinations had relapsed. We administered an antipsychotic agent, perospirone, to treat the auditory hallucinations, which disappeared, although the hyperemesis gravidarum persisted until childbirth. After childbirth, perospirone treatment was discontinued, and her auditory hallucinations did not relapse. The auditory hallucinations may have occurred as a result of complicated biological and psychosocial factors. Physicians should carefully evaluate psychotic symptoms, such as auditory hallucinations, not only during the postpartum period but also throughout the course of pregnancy.

Transient glyphosate encephalopathy due to a suicide attempt.

AIM: Glyphosate-containing herbicides are less toxic than paraquat and are one of the most widely used herbicides today. CASE PRESENTATION: We report a case of ingestion of a pesticide containing glyphosate in a suicide attempt. The patient was admitted to the psychiatric department because of persistent suicidal thoughts. He suffered from short-term memory impairment on day 3. Magnetic resonance imaging (MRI) showed swelling in the bilateral medial temporal lobes and hippocampi and high signal on T2-weighted images. Gradually, the patient's cognitive impairments improved, and he was discharged on day 33. CONCLUSION: A physician should examine the patient with the possibility of glyphosate encephalopathy in mind.

Effects of Antipsychotics on Arrhythmogenic Parameters in Schizophrenia Patients: Beyond Corrected QT Interval.

PURPOSE: Antipsychotic drugs have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect marker for proarrhythmic risk. Recently, improved methods, namely, QT dispersion (QTD), QTD ratio (QTDR), T wave peak-to-end interval (Tp-e), Tp-e/QT ratio and Tp-e/QTc ratio, have been regarded as proarrhythmic risk markers. We attempted to reevaluate the risk of sudden cardiac death due to antipsychotics use by measuring these improved evaluation methods. PATIENTS AND METHODS: We retrospectively evaluated QTc, QTD, QTDR, Tp-e, Tp-e/QT ratio and Tp-e/QTc ratio from the medical records of 410 patients with schizophrenia diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, or 5th Edition. Information on drugs administered was obtained from medical records. We investigated the correlation between each index on ECG and medication, such as antipsychotics, prescribed to participants with linear regression analysis. We also compared each index between 235 healthy controls and 235 patients matched for age and sex. RESULTS: Positive correlations between QTc and levomepromazine and brexpiprazole were identified. Levomepromazine and lithium were positively correlated with QTD. Levomepromazine, quetiapine, asenapine, clozapine and carbamazepine were positively correlated with QTDR. Levomepromazine, olanzapine, brexpiprazole and lithium were positively correlated with Tp-e. Olanzapine, brexpiprazole and lithium were positively correlated with the Tp-e/QT ratio. Olanzapine, brexpiprazole and lithium were positively correlated with Tp-e/QTc ratio. Significant differences in all indexes were noted between the patients and healthy controls. CONCLUSION: According to our results, the prediction of the risk of sudden cardiac death by each index was inconsistent. We should evaluate the predictive factor of ventricular arrhythmia according to various electrocardiogram indexes because QTc alone could not identify the risk of sudden cardiac death.

Successful Treatment With Lithium in a Refractory Patient With Periodic Catatonic Features: A Case Report.

BACKGROUND: Catatonia is a severe condition in patients. Electroconvulsive treatment or medication with benzodiazepines and/or antipsychotics are regarded as standard treatment. CASE PRESENTATION: We report a case of a patient with catatonic features in whom electroconvulsive treatment and benzodiazepine and/or antipsychotic medications failed to achieve efficacy. Additional treatment with lithium ameliorated catatonia. CONCLUSION: We concluded that lithium is an optional treatment in patients in whom standard treatment failed.

Bickerstaff's Brainstem Encephalitis Suspected as Functional Neurologic Disorders.

Functional neurologic disorders feature nervous system symptoms that cannot be explained by a neurological disease or other medical condition. The patient described here was a 21-year-old Japanese woman who was initially diagnosed with a functional neurologic disorder based on numbness and weakness of the limbs with no abnormalities in routine examinations. Further detailed examinations revealed monocytes in cerebrospinal fluid (CSF), and electroencephalography revealed widespread, low-voltage, slow waves with concentrated spindle waves. Thus, encephalitis was suspected, and steroid pulse therapy was initiated. Her symptoms subsequently improved. Afterward, CSF analysis was positive for serum anti-GQ1b IgG antibodies. We made a final diagnosis of Bickerstaff's brainstem encephalitis (BBE). Our report describes the difficult differentiation of functional neurologic disorders from BBE. Physicians and psychiatrists should be aware of BBE.

Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting.

OBJECTIVE: Some antidepressants have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect biomarker for proarrhythmic risk. Therefore, we reevaluated the risk of sudden cardiac death due to antidepressants using improved. METHODS: , namely, QT dispersion (QTD), T wave peak-to-end interval (Tp-e), and Tp-e/QT ratio. METHODS: We compared the effects of antidepressants on QTc (QT/RR1/3), QTD, Tp-e, and Tp-e/QT ratio in 378 patients with mood disorder. We also compared each index between 165 healthy controls and 215 randomly selected age-matched patients. RESULTS: Age (p<0.01), sex (p<0.05), tricyclic antidepressant (TCA) use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly associated with a prolonged QTc. We also found that age (p<0.01), TCA use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly prolonged QTD. However, there was no correlation between each variable and Tp-e or Tp-e/QT ratio. Significant differences in QTc and QTD were found between the patients and healthy controls. CONCLUSION: From our results, prediction of risk of sudden cardiac death by QTD, Tp-e, or Tp-e/QT ratio was inconsistent. Increased QTD may be more suitable for predicting sudden cardiac death due to antidepressants.

Phosphoserine phosphatase activity is elevated and correlates negatively with plasma d-serine concentration in patients with schizophrenia.

The pathophysiology of schizophrenia may involve N-methyl-D-aspartate receptor (NMDAR) hypofunction. D-3serine and glycine are endogenous l-serine-derived NMDAR co-agonists. We hypothesized that the l-serine synthesis pathway could be involved in schizophrenia. We measured the activity of phosphoserine phosphatase (PSP), a rate-limiting enzyme in l-serine synthesis, in peripheral blood mononuclear cells of 54 patients with schizophrenia and 49 normal control subjects. Plasma amino acid (l-serine, d-serine, glycine, glutamine, and glutamate) levels were measured by high performance liquid chromatography. Peripheral blood mRNA expression levels of PHGDH, PSAT1, PSP, and SR, determined by quantitative real-time PCR were compared between patients and controls. PSP activity was higher in patients than in controls, especially in male patients. In male patients, the plasma l-serine concentration was higher than that in controls. In patients, PSP activity was negatively correlated with plasma d-serine and glycine levels. Furthermore, PSP activity was positively correlated with plasma l-serine concentration. These results were statistically significant only in male patients. PSP, PSAT1, and PHGDH mRNA levels were lower in patients than in controls, except when the PHGDH expression level was compared with ACTB expression. In summary, we found the l-serine synthesis system to be altered in patients with schizophrenia, especially in male patients.

QT is longer in drug-free patients with schizophrenia compared with age-matched healthy subjects.

The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene for schizophrenia. Additionally, the disturbance of autonomic control, which affects the QT interval, is known in schizophrenia. Therefore, we speculate that schizophrenic patients have characteristic features in terms of the QT interval in addition to the effect of antipsychotic medication. The QT interval of patients with schizophrenia not receiving antipsychotics (n = 85) was compared with that of patients with schizophrenia receiving relatively large doses of antipsychotics (n = 85) and healthy volunteers (n = 85). The QT interval was corrected using four methods (Bazett, Fridericia, Framingham or Hodges method). In ANCOVA with age and heart rate as covariates, patients not receiving antipsychotic treatment had longer QT intervals than did the healthy volunteers, but antipsychotics prolonged the QT interval regardless of the correction method used (P<0.01). Schizophrenic patients with and without medication had a significantly higher mean heart rate than did the healthy volunteers, with no obvious sex-related differences in the QT interval. The QT interval prolongation may be manifestation of a certain biological feature of schizophrenia.

Lung transplantation in a Japanese patient with schizophrenia from brain-dead donor.

We herein report a case of lung transplantation in a patient with schizophrenia. The findings show that patients with schizophrenia can be considered for lung transplant after careful evaluation of psychiatric status and indications.