Cross-modal associative memory impairment in schizophrenia.

Impaired associative memory function in patients with schizophrenia has received considerable attention. However, previous studies have primarily concentrated on unisensory materials, which limits our understanding of the broader implications of this impairment. In this study, we sought to expand on this knowledge by examining two types of associative memory domains in individuals with schizophrenia, leveraging both visual (Vis) and auditory (Aud) materials. A total of 32 patients with schizophrenia and 29 healthy controls were recruited to participate in the study. Each participant participated in an experiment composed of three paradigms in which different abstract materials (Aud-Aud, Aud-Vis, and Vis-Vis) were presented. Subsequently, the discriminability scores of the two groups were calculated and compared in different modal tasks. Results from the study indicated that individuals with schizophrenia demonstrated varying degrees of associative memory dysfunction in both the same and cross-modalities, with the latter having a significantly lower score than healthy controls (t = 4.120, p < 0.001). Additionally, the cross-modal associative memory function was significantly and negatively correlated with the severity of negative symptoms among individuals diagnosed with schizophrenia (r = -0.362, p = 0.042). This study provides evidence of abnormalities in the processing and memorization of information that integrates multiple sensory modalities in individuals with schizophrenia. This is of great significance for further understanding the cognitive symptoms and pathological mechanisms of schizophrenia, potentially guiding the development of relevant interventions and treatment methods.

Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) in first-episode schizophrenia patients: Rationale and trial design.

Accumulated studies have investigated pharmacological interventions for first-episode schizophrenia (FES) patients. However, studies on subsequent treatment steps, which are essential to guide clinicians, are largely missing. This Sequential Multiple-Assignment Randomized Trials comparing Antipsychotic Treatments (SMART-CAT) program intends to evaluate the effectiveness of commonly used antipsychotic drugs in FES patients. The major goals of this study are to examine: 1) what would be the optimal subsequent sequential treatment if the first antipsychotic drug failed; 2) whether clozapine could be used in those first-trial failed and have superior efficacy compared to other atypical antipsychotics. In this article we will report the detail protocol of SMART-CAT. The SMART-CAT is a randomized controlled clinical multicenter trial in which 9 institutions in China will participate. A total of 720 FES patients will be enrolled and followed up for 12 months in this study. The trial includes three treatment phases (each phase lasting for 8 weeks) and a naturalistic follow-up phase; participants who do well on an assigned treatment will remain on that treatment for the duration of the 12-month treatment period, while non-responders will move to the next phase of the study to receive a new treatment. Phase 1 is a randomized controlled trial; patients will be randomly assigned to one of the treatments with oral olanzapine, risperidone, amisulpride, aripiprazole or perphenazine. Subjects who fail to respond after 8 weeks will enter the phase 2 randomization. Phase 2 is an equipoise-stratified randomization trial, and patients will be randomly assigned to oral olanzapine, amisulpride or clozapine for 8 weeks. Subjects who fail to respond after phase 2 will enter an open label trial (phase 3); patients who receive clozapine in phase 2 and fail to respond will be assigned to an extended clozapine treatment or modified electroconvulsive therapy add-on therapy (Phase 3A). Patients who were not assigned to clozapine in phase 2 will be assigned to treatment with clozapine or another SGAs not previously used in phase 1 and 2 (Phase 3B). The primary outcome for the treatment phase is the treatment efficacy rate, which is defined as at least 40% reduction in Positive and Negative Syndrome Scale (PANSS) total score. We hypothesize that clozapine is more therapeutically effective than any other SGAs to patients who failed to meet efficacy criteria in Phase 1, and earlier treatment with clozapine can improve the functional outcomes of schizophrenia patients. As for the naturalistic follow-up phase, time to all-cause treatment failure, marked by its discontinuation is selected as the primary outcome, since it reflects both efficacy and side effects. The all-cause discontinuation is defined as discontinuing for any reasons, including poor efficacy, intolerance of adverse reactions, poor compliance and other reasons. The results of the SMART-CAT trial will provide evidence for the selection of antipsychotics in FES patients who fail to respond to the first trial of an antipsychotic drug. It will also provide evidence for the efficacy and safety of using clozapine in the early phase of schizophrenia treatment by comparing with other SGAs. The study is based on the combination of sequential therapy and dynamic therapy, which can be more suitable to assess the effectiveness of treatment options in the real-world clinical setting. As a result, we hope that this study can provide guidance for an optimal treatment algorithm in first-episode schizophrenia patients. Trial registration: ID NCT03510325 in ClinicalTrials.gov.

Neurochemical and brain functional changes in the ventromedial prefrontal cortex of first-episode psychosis patients: A combined functional magnetic resonance imaging-proton magnetic resonance spectroscopy study.

OBJECTIVE: Previous studies showed alterations of brain function in the ventromedial prefrontal cortex of schizophrenia patients. Also, neurochemical changes, especially GABA level alteration, have been found in the medial prefrontal cortex of schizophrenia patients. However, the relationship between GABA level in the ventromedial prefrontal cortex and brain functional activity in schizophrenia patients remains unexplored. METHODS: In total, 23 drug-naïve, first-episode psychosis patients and 26 matched healthy controls completed the study. The single voxel proton magnetic resonance spectroscopy data were acquired in ventromedial prefrontal cortex region, which was used as the seed region for resting-state functional connectivity analysis. The proton magnetic resonance spectroscopy data were processed to quantify the concentrations of GABA+, glutamine and glutamate, and N-acetylaspartate in ventromedial prefrontal cortex. Spearman correlation analysis was used to examine the relationship between metabolite concentration, functional connectivity and clinical variables. Pearson correlation analysis was used to examine the relationship between GABA+ concentration and functional connectivity value. RESULTS: In first-episode psychosis patients, GABA+ level in ventromedial prefrontal cortex was higher and was positively correlated with ventromedial prefrontal cortex-left middle orbital frontal cortex functional connectivity. N-acetylaspartate level was positively correlated with positive symptoms, and the functional connectivity between ventromedial prefrontal cortex and left precuneus was negatively associated with negative symptoms of first-episode psychosis patients. CONCLUSION: Our results indicated that ventromedial prefrontal cortex functional connectivity changes were positively correlated with higher local GABA+ level in first-episode psychosis patients. The altered neurochemical concentration and functional connectivity provide insights into the pathology of schizophrenia.

Research Progress in Biological Studies of Schizophrenia in China in 2017.

Schizophrenia is a severe mental disorder and its etiology and pathological mechanism are unknown. This article mainly introduces the progress of biological studies of schizophrenia in China in 2017, including neuroimaging, genetics, and immunology studies. It also introduces the research progress of high-risk psychotic syndrome and physiotherapy.