Schizophrenia (Heidelberg, Germany)最新文献

Auditory hallucination (AH) is a distressing and disabling symptom in patients with schizophrenia spectrum disorder, particularly in those who do not respond to antipsychotics. The aim of this study is to examine the efficacy of AVATAR (Audio Visual Assisted Therapy Aid for Refractory auditory hallucinations) therapy for medication-resistant AH in patients with schizophrenia spectrum disorder. A systematic search was conducted across five major databases for randomized controlled trials (RCTs) investigating AVATAR therapy for patients with medication-resistant AH, with control conditions such as treatment-as-usual (TAU), cognitive behavioral therapy (CBT), or supportive therapy. The primary outcome was AH severity improvement, measured by the Psychotic Symptom Rating Scale-Auditory Hallucination. The secondary outcomes were positive and negative symptoms (assessed using the Positive And Negative Syndrome Scale), quality of life, depression, anxiety, and acceptance (all-cause discontinuation). Additionally, we evaluated the long-term efficacy by examining the sustained effects after treatment discontinuation. Six RCTs (n = 675; 64.7% male; mean age 39.4 [SD 4.8] years) were included. AVATAR therapy was associated with AH improvement (mean difference [MD], -2.97; 95%CI: -4.03, -1.90) and positive symptoms reduction (MD, -1.13; 95%CI: -2.14, -0.11) compared to controls. It also showed efficacy in improving depressive symptoms, anxiety, and quality of life, with small-to-medium effect sizes. The three-month follow-up effects remained consistent with treatment effect at study endpoints across all outcomes. The all-cause discontinuation rate did not differ between AVATAR therapy and controls. Given its potential benefits, clinicians may consider implementing AVATAR therapy for patients with medication-resistant symptoms. However, the development of standardized treatment protocols or manuals is essential to ensure treatment fidelity and guide future clinical and research applications.

Immune-inflammatory mechanisms in schizophrenia have received widespread attention, but the levels of interleukin-10 (IL-10) and interleukin-19 (IL-19) and their associations with clinical symptoms in adolescent-onset schizophrenia (AOS) remain unclear. This study aimed to investigate serum IL-10 and IL-19 levels in AOS patients and their relationships with clinical symptoms. This cross-sectional study enrolled 83 drug-naïve first-episode AOS patients and 40 healthy controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Compared with healthy controls, AOS patients exhibited significantly decreased serum IL-10 levels (P = 0.007), elevated IL-19 levels (P = 0.014), and an increased IL-19/IL-10 (P < 0.001). Serum IL-10 levels in AOS patients were significantly negatively correlated with PANSS negative factor scores (r = -0.254, P = 0.020) and excitement/hostility factor scores (r = -0.348, P = 0.001), while the IL-19/IL-10 was positively correlated with excitement/hostility factor scores (r = 0.349, P = 0.001). Exploratory stratified analyses revealed significant negative correlations between IL-10 and excitement/hostility factor in both male patients (r = -0.432, P = 0.010) and female patients (r = -0.375, P = 0.009). Additionally, lower IL-10 levels were an independent predictor of AOS (RR = 0.808, 95%CI: 0.714-0.914, P = 0.001). AOS patients demonstrated an immune imbalance characterized by decreased serum IL-10, elevated IL-19 levels, and an increased IL-19/IL-10. IL-10 levels and the IL-19/IL-10 were closely associated with negative and excitement/hostility symptoms in AOS, with this association exhibiting sex differences. These findings suggest that IL-10 and the pro-inflammatory/anti-inflammatory balance may play an important role in the pathophysiological mechanism of AOS.

Antipsychotic-induced weight gain (AIWG) exhibits marked heterogeneity. We conducted a secondary analysis of the Chinese First-Episode Schizophrenia Trial, leveraging frequent body mass index (BMI) measurements over 12 months. Our aims were to identify latent BMI trajectories in first-episode schizophrenia (FES) patients treated with second-generation antipsychotics (SGAs) and to explore predictors of trajectory membership. Subjects in this study were from the Chinese First-Episode Schizophrenia Trial (CNFEST). After quality control, a total of 361 drug-naïve FES patients treated with olanzapine, risperidone, or aripiprazole were included. BMI was measured at 7 timepoints over 12 months. Latent class trajectory modeling (LCTM) was used to identify distinct BMI trajectories. Multinomial logistic regression was applied to detect predictors of trajectory membership. Four BMI trajectories were emerged, including Low Baseline BMI with Rapid Increase (LBRI) (6.1%, +3.5kg/m² within the first 3 months), Moderate Baseline BMI with Gradual Increase (MBGI) (33.8%, steady rising during 9 months), and Low/High Baseline BMI with Slight Increase (LBSI/HBSI) (46%/14.1%, Minimal change (<1.5 kg/m²)). Baseline BMI (χ² = 144.5, p < 0.001) was the strongest predictor of the LBRI trajectory. A numerically higher, though not statistically stable, odds were observed for olanzapine vs. aripiprazole (OR = 20.4, 95% CI = 2.48-166.67). Shorter duration of untreated psychosis (DUP < 1 year) (OR = 4.12, 95% CI = 1.31-12.93) and lower education (OR = 5.40, 95% CI = 1.19-24.52) further increased LBRI risk. A high-risk subgroup (LBRI) with rapid early weight gain was identified, driven by olanzapine use, shorter DUP, and lower educational attainment. These findings advocate for dynamic risk stratification and early preventive interventions in vulnerable FES patients (Trial Registration: This trial was registered at ClinicalTrials.gov (Identifier: NCT01057849) on January 26, 2010).

Automated syntactic markers distinguished patients with first-episode psychosis from healthy controls in a Brazilian Portuguese-speaking sample, achieving 81% cross-validated accuracy (AUC = 0.86). These findings largely replicate prior results in Dutch, underscoring the potential of automated syntactic measures to identify early psychosis across languages, illness stages, and speech elicitation tasks.

Despite evidence supporting the involvement of family members in early-intervention services for psychosis, rates of family engagement have been relatively low, and disparities exist. This study investigated the acceptability, feasibility, and preliminary impact of Family Motivational Engagement Strategy (FAMES) with family members of clients enrolled in coordinated specialty care (CSC). A feasibility and acceptability pilot study of FAMES was conducted in five CSC programs for FEP using a modified stepped-wedge design. FAMES consists of brief weekly contacts based on communication preferences (i.e., phone, text messages, email) and the use of culturally responsive strategies over 12 weeks. Assessments were completed at baseline and weeks 4, 8, and 12. Primary outcomes were feasibility and acceptability, and secondary outcomes were engagement in FAMES and CSC. Forty-three participants were recruited (approximately 85% of the target recruitment sample of 50) and 72% (n = 31) completed all 12 weeks. Participants reported high rates of satisfaction with FAMES. Regarding engagement, 86% of scheduled FAMES appointments were attended, and no significant ethnoracial differences in engagement were observed. Exploratory analyses revealed engagement in FAMES was associated with engagement in CSC. Findings demonstrated the feasibility and acceptability of delivering FAMES within CSC settings for family members/support persons. A subsequent study is needed to examine the efficacy and real-world implementation of FAMES.

Abnormal neurotransmitter regulation plays a role in the pathogenesis of Schizophrenia (SCZ), and the presence of brain tissue-like aberrant expression in the partial transcriptome of peripheral blood leukocytes from patients with SCZ suggests that these aberrantly expressed genes could be potential diagnostic markers. We designed a case-control study to analyze the association between the expression levels of mRNAs and SCZ in peripheral blood leukocytes and to explore their potential value as diagnostic biomarkers for SCZ. Differentially expressed mRNAs associated with neural signaling pathways were screened by RNA sequencing in a small set, comprising 9 patients with SCZ and 20 controls. A case-control study that included 217 cases and 217 controls was further conducted to verify these mRNAs. The differential expression analysis between cases and controls was performed, followed by restricted cubic spline regression analysis. Gene expression score (GES) was constructed for differentially expressed genes to assess their diagnostic value as biomarkers. In SCZ patients, there were higher expression levels of CREB5, PPP3R1 and PPP1CB (P < 0.05) than in controls. Furthermore, DUSP1 and MAPK13 downregulated in undifferentiated SCZ and acute schizophrenia-like psychotic disorder (P < 0.05), PPP3R1 expression upregulated in paranoid SCZ, undifferentiated SCZ and acute schizophrenia-like psychotic disorder (P < 0.01), and CREB5 exclusively upregulated in paranoid SCZ (P = 0.001), respectively. The risk of SCZ was nonlinearly correlated with DUSP1, GNG10, GNG7, PRKACA, CREB5, PPP3R1 and PPP1CB (P_overall < 0.05, P_nonlinear < 0.05). Meanwhile, incorporating these 7 genes into the GES improved the model's area under curve to 0.743, significantly enhancing the diagnostic discriminatory ability for SCZ.

Metabolic syndrome (MetS) is highly prevalent among individuals with schizophrenia. However, substantial regional variation exists, and evidence from large samples of hospitalized patients in China remains limited. This study aimed to estimate the prevalence of MetS and to explore its associated factors among individuals with schizophrenia in China. We included 3042 participants with schizophrenia from 25 hospitals in Zhejiang Province from April to December 2022. MetS was defined according to the Chinese Diabetes Society (CDS) criteria, the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and the International Diabetes Federation (IDF) criteria. The prevalence of MetS was estimated using the Clopper-Pearson method, and generalized additive models were used to fit smoothed age-specific prevalence curves. Multivariate logistic regression was used to explore potential factors associated with MetS. The overall prevalence of MetS was 34.9% (95% confidence interval [CI]: 33.2-36.7%), 42.6% (40.9-44.4%), and 38.9% (37.2-40.7%) based on the CDS, NCEP ATP III, and IDF criteria, respectively. The prevalence of MetS was significantly higher in female participants with schizophrenia compared to their male counterparts when applying the NCEP ATP III or IDF criteria. In addition, after reaching the age-specific peak, MetS prevalence declined in male participants but stabilized in females. High BMI (OR: 1.30 [1.27-1.33]) and comorbid endocrine diseases (OR: 1.79 [1.48-2.17]) were associated with increased odds of MetS. Metabolic syndrome is highly prevalent among individuals with schizophrenia, regardless of the diagnostic criteria used. Early identification and screening of metabolic abnormalities in individuals with schizophrenia should be considered.

MicroRNAs (miRNAs) are critical regulators of neurodevelopment and are implicated in the pathogenesis of schizophrenia. Schizophrenia is increasingly recognized as a neurodevelopmental disorder, with most cases emerging during late adolescence and early adulthood, which is a critical period of brain maturation. However, the study of miRNAs during this phase has been limited by the challenges of postmortem brain analysis. Neuron-derived extracellular vesicles (NEVs) have recently been proposed for investigating brain-derived molecular profiles. In this study, NEVs were enriched from plasma using the L1CAM antibody in patients with recent-onset schizophrenia (ROS) within 5 years of onsets and chronic-phase schizophrenia (CS). The miRNA profiles of these NEVs in patients with ROS and CS were compared with those of age-and sex-matched healthy controls. Differential expression analysis revealed miRNA changes specific to the recent-onset phase as well as possible pathophysiological mechanisms transitioning from the recent-onset to the chronic phases. These findings provide novel insights into the role of miRNAs in neurodevelopmental abnormalities associated with schizophrenia onset. This study highlights the utility of NEVs as a tool for accessing brain-derived miRNA profiles and diagnostic biomarkers and underscores the importance of an onset period as a critical window for understanding the molecular underpinnings of schizophrenia.

Cognition in schizophrenia is difficult to assess in clinical settings due to the time required to administer traditional pen-and-paper tests, among other factors. Digital remote assessments completed on a smartphone offer an alternative that can reduce the burden on healthcare staff and patients, in addition to providing more nuanced cognitive profiles, especially when used in conjunction with smartphone data such as sleep. Building on previous work using the mindLAMP research app in international contexts, this paper presents a global multi-site pilot study to explore the validity of the app's digital cognitive assessments as proxies for traditional in-person assessments such as the gold standard MATRICS Consensus Battery (MCCB). Across one site in the U.S. (Boston) and two sites in India (Bangalore and Bhopal), a total of 56 participants with diagnoses of early-course schizophrenia or schizoaffective disorder were recruited between September 2024 and March 2025 to engage with the mindLAMP app for 30 days. Participants completed 2-3 different cognitive tasks and surveys each day; at the beginning and the end of this period, participants also took the MCCB and surveys related to their diagnosis. mindLAMP cognitive assessments were scored using different metrics that combine speed and accuracy, and correlation analyses were run on these metrics and MCCB domains. Of the scoring metrics used, the Rate-Correct Score (RCS) most consistently correlates with baseline MCCB domains corrected for age, gender, and education. Moderate test-retest reliability was observed across certain cognitive assessments such as a mobile version of Trails-Making Test A and Symbol Digit Substitution, which agrees with previous research done by Keefe et al.; poor test-retest reliability, in contrast, was observed across assessments such as Spatial Span. Additionally, we conducted exploratory mediation analyses using sleep data to see if sleep mediates between the Ecological Momentary Assessment (EMA) survey scores and performance on select digital cognitive assessments on mindLAMP. Our results support the initial accessibility, validity and reliability of using smartphones to assess cognition in schizophrenia. Future research to develop additional smartphone-based cognitive tests, as well as with larger samples and in other psychiatric populations, is warranted.

We aimed to examine the association between gut permeability biomarkers (LBP, sCD14) and insulin resistance (IR) in schizophrenia. In this cross-sectional study of 91 patients, IR (HOMA-IR ≥ 3.0) was associated with higher LBP, C-reactive protein, body mass index (BMI), and lower physical activity. Logistic regression identified LBP and BMI as independent risk factors, whereas physical activity was protective. These findings suggest altered gut permeability could influence glucose metabolism dysfunction in schizophrenia.