The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects

BackgroundThe effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis.MethodsImaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed.ResultsDaily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes.DiscussionA large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication

White matter microstructural alterations across four major psychiatric disorders : mega-analysis study in 2937 individuals

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders

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

Regulation of the Hydrolytic Activity of Mg²⁺-Dependent Phosphatase Models by Intramolecular NH···O Hydrogen Bonds

Magnesium-dependent phosphatase models containing intramolecular NH···O hydrogen bonds were synthesized and structurally characterized by X-ray analysis. The Mg–O bond distances varied with the mode of the hydrogen bonds. ¹H NMR spectra in nonpolar solvents revealed that the acidity of the coordinated water molecule was regulated by the hydrogen bonds. Further, stoichiometric hydrolysis of phosphoric ester significantly depended on the hydrogen bonds. Zinc analogues showed similar but smaller dependencies, which suggest the indispensable role of Mg²⁺ ion in the activation of the enzymes