ABSTRACT Background Schizophrenia is characterized by positive symptoms, negative symptoms, and cognitive impairment and is primarily treated with antipsychotic medications. However, a subset of patients responds inadequately to treatment and is classified as having treatment‐resistant schizophrenia (TRS). The prevalence of TRS among patients with schizophrenia remains insufficiently characterized. This study aimed to determine the prevalence of TRS using nationwide data and standardized diagnostic criteria. Methods This study included patients with schizophrenia who were discharged between 2016 and 2024 from 205 institutions participating in the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project and authorized to prescribe clozapine. TRS was defined according to standardized diagnostic criteria used in Japan. The prevalence of TRS was calculated among patients who underwent a TRS examination by their treating psychiatrist. Results Among 18 914 patients, 9870 (52.2%) underwent a TRS examination. Among these 9870 patients, 2819 were classified as having TRS, corresponding to a prevalence of 28.6%. Among the 2819 patients with TRS, 1307 were prescribed clozapine at discharge, corresponding to a clozapine treatment rate of 46.4%. Conclusions This study had the largest sample size among single‐cohort studies investigating the prevalence of TRS. The prevalence of TRS was 28.6% among patients with schizophrenia who underwent a TRS examination and was nearly identical to the pooled prevalence reported in studies at low risk of bias in a previous meta‐analysis. These findings may provide important evidence regarding the prevalence of TRS in routine clinical practice.
AIM
Neuroinflammation has been implicated in the pathogenesis of major depressive disorder (MDD), with interferon regulatory factor 1 (IRF1) playing a potential role. MicroRNAs (miRs) are also involved in MDD through posttranscriptional regulation of gene expression. This study investigated whether miR-20a-5p regulates IRF1 in MDD.
METHODS
IRF1 mRNA and miR-20a-5p expression levels were measured by qPCR in postmortem hippocampi from 14 MDD subjects and 14 controls, and in chronic social defeat stress (CSDS) mice. Their regulatory relationship was examined in HEK293 cells using miR-20a-5p overexpression and a dual-luciferase assay. Neuro2a cells treated with DMSO were used to evaluate the effects of cellular stress on Irf1 and miR-20a-5p expression.
RESULTS
IRF1 mRNA and miR-20a-5p expression levels were significantly increased in both MDD hippocampi and CSDS mice. Luciferase assays showed that miR-20a-5p directly targeted the conserved seed sequence within the IRF1 3'-UTR and suppressed IRF1 expression. During the early phase of cellular stress, Irf1 mRNA was upregulated, whereas miR-20a-5p was downregulated, suggesting that stress initially induces Irf1 expression, followed by secondary regulation of miR-20a-5p.
CONCLUSION
IRF1 mRNA expression was increased in the hippocampus of both MDD subjects and CSDS mice. Moreover, miR-20a-5p directly targeted the IRF1 3'-UTR, supporting a potential miR-20a-5p-IRF1 regulatory axis involved in inflammatory signaling in MDD. However, its functional significance in vivo remains to be determined.
Mariko Okano, Yuta Yoshino, Anuj K. Verma et al.· Psychiatry and Clinical Neur...· 0 citations
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