Relationships between brain-derived neurotrophic factor, clinical symptoms, and decision-making in chronic schizophrenia: data from the Iowa Gambling Task

The levels of brain-derived neurotrophic factor (BDNF) are significantly decreased in patients with schizophrenia and correlate with impairments in cognitive function. However, no study has investigated the relationship between the serum BDNF levels and decision-making. We compared patients with schizophrenia to healthy controls with respect to their decision-making ability and serum BDNF levels. Eighty-six chronic schizophrenia patients and 51 healthy controls participated in this study. We controlled for gender, age, and estimated intelligence quotient (IQ), and we investigated the differences in decision-making performance on the Iowa Gambling Task (IGT) between the schizophrenia patient and control groups. We also compared the IGT scores, the serum BDNF levels, and the clinical symptoms between the groups. The IGT scores of the schizophrenia patients were lower than those of the controls. A negative correlation was detected between the mean net scores on the trials in the final two blocks and the serum BDNF levels（p<0.05）. Multiple regression analysis revealed that depressive symptoms and the serum BDNF levels were significantly associated with the mean net scores on the trials in the final two blocks. Based on these results, impaired sensitivity to both reward and punishment is associated with depressive symptoms and reduced serum BDNF levels in chronic schizophrenia patients and may be related to their poor performance on the IGT

Clozapine and Antipsychotic Monotherapy

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription

EGUIDE project and treatment guidelines

Background Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. Aims The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. Method A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. Results All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. Conclusions All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists

EGUIDE project and treatment guidelines

Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1‐day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self‐completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders

Effects of Continuing Oral Risperidone vs. Switching from Risperidone to Risperidone Long-Acting Injection on Cognitive Function in Stable Schizophrenia Patients: A Pilot Study

ObjectivesRisperidone is the first new generation antipsychotic drug to become available as a long-acting injection (LAI). The purpose of this study was to evaluate the effects of switching from oral risperidone to risperidone LAI (RLAI) on cognitive function in stable schizophrenia patients compared with the effects of continuing oral risperidone.MethodsSixteen stable patients who had received risperidone monotherapy for at least 3 months were enrolled (the RLAI group). Before and 24 weeks after switching to RLAI, the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Positive and Negative Syndrome Scale (PANSS) were administered. To exclude the possibility of learning effects on the BACS-J results, 14 patients with stable schizophrenia who continued oral risperidone treatment were also assessed (the RIS group).ResultsThe two groups did not differ with respect to changes in the PANSS score, and no emergent side effects, including extrapyramidal symptoms, were observed. The BACS-J score for verbal memory exhibited greater improvement in the RLAI group than in the RIS group (p = 0.047).ConclusionThe results of this preliminary study suggest that switching from oral risperidone to RLAI may improve verbal capability more than continuing with oral risperidone. However, these findings must be replicated in a larger, double-blind study

Serum Brain-Derived Neurotrophic Factor, and Plasma Catecholamine Metabolites in People with Major Depression: Preliminary Cross-Sectional Study

BackgroundThere are complicated interactions between catecholaminergic neurons and brain-derived neurotrophic factor (BDNF) in the brain. However, no reports have addressed the relationship among 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and BDNF in the blood.ObjectiveThis paper sought to investigate correlations between serum BDNF and plasma levels of MHPG and HVA in people with major depression (MD).Materials and methodsA total of 148 patients (male/female 65/83, age 49.5 ± 12.1 years old) who satisfied criteria for MD based on the Diagnostic and Statistical Manual of Mental Disorders IV were enrolled in the present study. Plasma levels of MHPG and HVA were analyzed using high-performance liquid chromatography, and serum BDNF was measured using ELISA.ResultsNo interactions were observed between plasma HVA levels (mean ± SD = 4.5 ± 1.5 ng/mL) and age, sex, HAMD scores, or serum BDNF levels (mean ± SD = 9.8 ± 2.9 ng/mL). No correlations were not also observed between plasma MHPG levels (mean ± SD = 5.9 ± 2.1 ng/mL) and age, sex, the HAMD17 scores (mean ± SD = 22.2 ± 2.9 ng/mL), or serum BDNF levels. Serum BDNF levels were negatively associated with HAMD17 scores.ConclusionThe results suggest that there are no significant correlations between catecholamine metabolites and BDNF in the blood for MDD patients

The Impact of Aging, Psychotic Symptoms, Medication, and Brain-Derived Neurotrophic Factor on Cognitive Impairment in Japanese Chronic Schizophrenia Patients

Background: Cognitive impairment in schizophrenia can result in considerable difficulty in performing functions of daily life or social rehabilitation. Cognitive impairment in schizophrenia is related to various factors, such as the psychotic severity, aging, medication, and brain-derived neurotrophic factor (BDNF). To date, however, no studies investigating the impact of these factors on cognitive functioning in chronic schizophrenia patients have been performed.Objective: The aim of this study is to identify those factors that influence the cognitive functioning in patients with chronic schizophrenia.Methods: Sixty-five of 116 long-term hospitalized chronic schizophrenia patients (63.8 ± 12.1 years old, M/F = 29/36) were enrolled this cross-sectional study. We investigated the relationship among the patients' age, psychotic severity, treatment medication, serum BDNF levels, and cognitive functioning (measured by the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia; BACS-J). Additionally, we performed a multivariable linear regression analysis.Results: According to the partial correlation analysis, certain parameters [i.e., age, chlorpromazine (CP) equivalent, biperiden (BP) equivalent, and serum BDNF] were significantly correlated with cognitive functioning, including working memory (WM), motor function (MF), attention and processing speed (AP), and executive function (EF). For the multivariate analysis, the MF component, which had the highest correlation, was selected as the dependent variable, and the independent variables included age, Manchester Scale for chronic psychosis (ManS) total score, CP equivalent, BP equivalent, serum BDNF, estimated full scale IQ, and years of education. According to the multiple regression analysis of this model, R (multiple regression coefficient) was 0.542, the adjusted R2 (coefficient of determination) was 0.201, and only BP equivalent (β = −0.305, p = 0.030), but not age, ManS score, CP equivalent, or serum BDNF, could significantly explain MF at the 5% significant level.Conclusion: In conclusion, aging, medication (administering more antipsychotics or anticholinergics), and serum BDNF concentration are significantly correlated with cognitive dysfunction in chronic schizophrenia patients but not with the severity of psychotic symptoms. Furthermore, only the anticholinergic dosage had a significant causal relationship with MF. Thus, the use of anticholinergics in chronic schizophrenia patients with deteriorating cognitive functioning must be reconsidered