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Altered brain activity preceding behavior may reflect a reduced ability to suppress the sensory consequences of self-generated actions in schizophrenia. The corollary discharge (CD) mechanism has been proposed to underlie this process. In the present study, we investigated CD by analyzing the readiness potential (RP) and its relationship to auditory N1 suppression in patients with schizophrenia compared to healthy controls (HCs). We also examined the association between RP activity and anomalous self-experiences (ASEs). Event-related potentials were recorded from 48 patients with schizophrenia and 55 HCs during a vocalization paradigm including talk and listen conditions. RP amplitude and N1 suppression were quantified as the amplitude difference between listen and talk conditions. Regression analyses assessed the relationship between these components within each group and examined associations between RP and N1 amplitudes and ASEs, measured using the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE) scale, in the schizophrenia group. In the talk condition, HCs showed greater RP amplitude compared with the listen condition, a difference that was absent in the schizophrenia group. In HCs, this RP increase was followed by suppression of the N1 component. A significant correlation between RP amplitude and N1 suppression was observed in HCs but not in patients. Importantly, reduced N1 suppression in patients with schizophrenia was associated with higher IPASE scores. These findings suggest that schizophrenia involves impairments in early cortical processes related to efference copy and corollary discharge mechanisms, reflected in reduced RP amplitude and the lack of coupling with N1 suppression. Such alterations may contribute to deficits in sensory prediction and to anomalous self-experiences in schizophrenia.
Artificial intelligence (AI) has been increasingly applied in schizophrenia research, yet a bibliometric overview of its global development and evolutionary trends remains lacking. Based on the Web of Science Core Collection (WoSCC), a bibliometric analysis was conducted on AI‑related schizophrenia studies published from 2005 to 2025. A total of 1,839 publications were included, and trends, countries, institutions, authors, journals, and research hotspots were analysed. Annual publications grew rapidly from 2 in 2005 to 374 in 2025, consistent with the expansion of AI research. The U.S., China, and England were the most productive and influential countries. The U.S. dominated global collaboration, while Chinese institutions showed strong domestic links but limited international partnerships. Leading institutions included the University of London, King's College London, and Harvard University. Nikolaos Koutsouleris and Vince D. Calhoun were the top authors. Key journals included Frontiers in Psychiatry, Schizophrenia Research, and Schizophrenia Bulletin, with NeuroImage as the top co-cited journal. Keyword analysis showed early focus on machine learning, risk assessment, and brain biomarkers based on functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG). After 2016, deep learning became dominant in diagnosis. Recently, natural language processing has emerged for risk prediction, indicating a shift toward multimodal AI applications. AI applications in schizophrenia have expanded exponentially with a clear evolution from machine learning to deep learning. The global collaboration pattern is imbalanced, and future research will advance toward multi‑modal, predictive, and precise intelligence.
Stigma toward individuals with schizophrenia is well documented, yet the extent to which stigmatizing views are present in media remains understudied. This study investigates sentiment and violence-related content in US news coverage. We hypothesize that media with schizophrenia-related keywords will have higher negative and lower positive ratings, and more violent ratings than news for illnesses of comparable burden. We conducted an observational comparative content analysis on 116 866 news transcripts from CNN, Fox News, and MSNBC (2016-2023). Sentiment ratings were derived using a roBERTa large language model, and violence-related language was measured using a dictionary-based natural language processing tool (LIWC-22). News related to schizophrenia demonstrated significantly higher negative sentiment (β = 0.078, t (4061) = 6.85, P < .001), lower positive sentiment (β = -0.10, t (4061) = -11.55, P < .001), and higher violent content (β = 0.14, t (4061) = 3.31, P < .001) compared to news on comparable illnesses. Additionally, schizophrenia-related keywords were used in clinical contexts significantly less often (SZ = 48.49%, ILL = 97.84%, Χ2(1) = 1276.4, P < .001). The results indicate a pervasive association between schizophrenia and negative, violent language in media, reinforcing existing stigma. These findings highlight a need for interventions targeting media portrayal to reduce public stigma against individuals with schizophrenia.
Individuals with schizophrenia report that time can feel discontinuous. Difficulties in benefiting from the passage of time at the level of hundreds of milliseconds are associated with the sense of self. However, time continuity might require millisecond-level processing. Here we leverage sequential effects in a synchrony judgment task to test whether individuals with schizophrenia and controls benefit from increased delays in the order of tens of milliseconds. We re-analyzed 3 datasets (65 individuals with schizophrenia and 67 controls). Two visual stimuli appeared simultaneously or with a stimulus onset asynchrony (SOA, 8-96 ms). Rather than comparing sensitivity in asynchrony detection, we contrasted performance when the SOA increased, remained identical, or decreased from the previous to the current trial. In a control masking task, 19 individuals with schizophrenia and 19 controls located a masked target. Performance improved for all participants when the SOA increased (and the task became easier), but more so for controls than for individuals with schizophrenia. These results were replicated across datasets and were specific to trials in which SOA increased on consecutive trials. This effect persisted even when SOAs were frequently identical and when we controlled for SOA magnitude. The group difference was specific to temporal judgments and was not observed in the masking task. These findings reveal a difficulty for individuals with schizophrenia to benefit from delay signals at the millisecond level, which we suggest underlies their experience of time fragmentation.
Elevated postmortem iron in Brodmann areas 10-11 has recently been linked to schizophrenia. Although in vivo studies have linked subcortical iron abnormalities to disease-related striatal hyperdopaminergia, in vivo cortical iron alterations have not been previously examined. We therefore used neuroimaging to test whether cortical iron is elevated in individuals with schizophrenia and whether this correlated with mesostriatal dopamine function. We acquired quantitative susceptibility mapping magnetic resonance imaging (MRI) to measure magnetic susceptibility (χ), a marker of iron, in 149 participants aged 18-45 (73 with schizophrenia and 76 matched healthy controls). Subsets of patients with schizophrenia underwent [18F]-DOPA PET to estimate striatal dopamine synthesis capacity (n = 39) and neuromelanin-sensitive MRI of the dopaminergic midbrain (n = 68), as neuromelanin is a byproduct of dopamine synthesis. Primary analyses showed no significant case-control differences in χ in the whole cortex (P = .675) or Brodmann areas 10-11 (P = .537). Exploratory analyses examined χ for 360 cortical regions, correcting for multiple comparisons. Two left temporo-parieto-occipital junction regions showed significantly elevated χ in schizophrenia: the posterior temporo-parieto-occipital junction the posterior temporo-parieto-occipital junction (d = 0.752, P < .001) and the superior temporal visual area (d = 0.638, P = .034). Mean χ across these regions inversely correlated with dopamine synthesis capacity in the associative (r = -0.37, P = .048) and limbic (r = -0.34, P = .048) striatum, and with neuromelanin-sensitive MRI values in the dopaminergic midbrain (r = -0.35, P = .005), corrected for multiple comparisons. This study provides the first in vivo evidence of elevated cortical iron in schizophrenia and links this to mesostriatal dopamine dysfunction.
Schizophrenia is a leading global disability, with severe treatment gaps in low-resource settings. Community-based rehabilitation (CBR) is promising but lacks robust evidence on its impacts on healthcare utilization. We conducted a cluster-randomized controlled trial across 18 urban and rural subdistricts in Weifang City, Shandong province, China, enrolling 334 participants with schizophrenia. Communities were randomly assigned to receive either facility-based care (FBC) enhanced with CBR (n = 172) or standard FBC alone (n = 162). The main outcomes of this study included outpatient/inpatient utilization, costs, and self-treatment over 6- and 12-month follow-up periods, collected through medical insurance claims and structured questionnaires. We systematically monitored intervention quality using the validated Comprehensive Psychotherapeutic Interventions Rating Scale. At 6 months, CBR participants had significantly lower outpatient costs vs. controls (total: -CNY748.6 [82.4% reduction], 95%CI, -1124.3 to -373.0; schizophrenia-specific: -CNY529.0 [79.1% reduction], -833.5 to -224.4) and reduced out-of-pocket (OOP) costs (total: -CNY216.9; schizophrenia-related: -CNY113.2). By 12 months, inpatient cost reductions emerged (total: -CNY1710.4 [78.2% reduction]; OOP: -CNY405.8 [78.1% reduction]) despite similar admission rates. Self-treatment increased (0.77 more episodes) with no cost differences. Higher quality predicted greater outpatient visit reductions at 12 months (β = -0.10) and inpatient visit reductions at 6 months (β = -0.21), with group dynamics and directive behaviors most beneficial. CBR significantly reduces healthcare costs and improves self-management. Quality-driven effects on utilization support scaled implementation in resource-limited settings, particularly via group-based approaches. Integrating high-quality CBR is critical to curb the rising economic burden in low-resource countries. ClinicalTrials.gov identifier: ChiCTR2200066945.
Patients with schizophrenia spectrum disorders have elevated cardiovascular risk with obesity and deranged metabolic profiles associated with antipsychotic usage, bearing significant tolls on chronic morbidity and mortality. The present study aims to evaluate the efficacy and tolerability of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in improving weight control and metabolic profile in atypical antipsychotics-treated patients with schizophrenia spectrum disorders. This double-blind, randomized, placebo-controlled trial studied overweight or obese adults with schizophrenia spectrum disorders (non-diabetic or pre-diabetic) who were taking atypical antipsychotics. Participants recruited from a specialist clinic of a regional public service were randomized to receive empagliflozin or placebo for 16 weeks, in combination with standardized lifestyle intervention through psychoeducation. The primary outcomes were changes in body weight and body mass index (BMI). Changes in other metabolic parameters were examined as secondary outcomes. Linear mixed models were used to study the differences in outcomes between the active and placebo arms. Of the 52 patients undergoing randomization, the SGLT2i group had significant reductions in body weight (-1.53 kg; 95% CI, -2.60 to -0.47), BMI (-0.53 kg/m2; 95% CI, -0.91 to -0.15), fasting glucose (-0.40 mmol/L; 95% CI, -0.65 to -0.15), and glycated hemoglobin A1c (-0.11%; 95% CI, -0.21 to -0.02) compared with the placebo group (P-values <.05). Adverse events and dropout rates were similar between the 2 groups. The combined approach of empagliflozin and lifestyle intervention improved weight control and glucose metabolism among patients with schizophrenia spectrum disorders receiving atypical antipsychotics.
Schizophrenia treatment in young people involves complex pharmacological decisions, yet sex-specific prescribing patterns and pandemic impacts remain poorly understood. We hypothesized that prescribing trends would differ systematically by sex and show pandemic-related disruptions. This population-based cohort study analyzed 8092 individuals aged 15-29 years with schizophrenia-spectrum disorders in Hong Kong (2011-2023) using electronic health records from the Hospital Authority system. We examined temporal trends in 11 medication subclasses using generalized least squares models with autoregressive correlation structures, sex differences using interaction terms, and COVID-19 impacts using interrupted time series (ITS) analysis with adjustment for age and comorbidity. After covariate adjustment, all medication subclasses increased over time (0.05-3.71 percentage points annually), indicating universal treatment intensification. Males showed steeper increases than females in 5 subclasses after adjustment, with 18 of 21 specific agents increasing significantly more in males. Period-level pandemic comparisons showed minimal effects, but ITS analysis revealed substantial COVID disruptions in 5 medication subclasses namely oral first-generation antipsychotics, injectable second-generation antipsychotics, serotonin and norepinephrine reuptake inhibitor, Z-hypnotics, and benzodiazepines. Young people with schizophrenia experienced universal treatment intensification with males receiving more intensive pharmacotherapy after controlling for confounders. The pandemic produced complex sex-specific disruptions masked by aggregate analyses. Whether these prescribing patterns represent appropriate individualization or systematic care variation remains unknown, highlighting the critical need for studies linking prescribing patterns to functional outcomes and quality of life.
First-person accounts (FPAs) provide multi-faceted insights into the lived social experiences of schizophrenia. We examined FPAs and third-person accounts (TPAs) using automated linguistic and network analyses to extract narrative patterns in relation to interpersonal difficulties. Narratives from 279 articles published in Schizophrenia Bulletin (1979-2025) were screened to identify 133 FPAs and 44 TPAs. Schizotypal Personality Questionnaire was used to assess syndromes of schizotypy expressed in the narratives. At least one cognitive-perceptual syndrome (ideas of reference, odd beliefs, magical thinking) was detected in every FPA (n = 133). Interpersonal difficulties (social anxiety, no close friends, constricted affect) were detected in 56 FPAs and designated as the "interpersonal difficulties" group. We used the Linguistic Inquiry and Word Count software to extract interpersonally relevant features: authenticity, emotional tone, pronoun use, social behavior, and confidence. Linguistic features of narratives in FPAs with and without interpersonal difficulties were compared using network analysis. Greater authenticity and lower confidence were detected in FPAs compared to TPAs. FPAs contained fewer social words and more "I" words than TPAs. FPAs with interpersonal difficulties were longer, more negative, and less linguistically formal than FPAs without interpersonal difficulties. Network analysis indicated a link between interpersonal difficulties and "voices." Narratives categorized by interpersonal difficulties exhibit distinct linguistic signatures revealed through automated linguistic tools and network analyses. Despite the vast range of topics in FPAs, these computational methods provide a robust quantitative framework for validating the lived experience of negative syndrome in schizotypy.
Our initial smaller study and other recent research suggest that adding a physical exercise program to cognitive training has promise for enhancing the impact on attention and overall cognition. We hypothesized that this would be the case even compared to adding a healthy living training program. In a randomized clinical trial of individuals with a recent first episode of schizophrenia, we provided cognitive training, 4 h/week for 6 months for all participants. Half were randomized to a physical exercise program and half to a healthy living group. The MATRICS Consensus Cognitive Battery was administered at baseline, 3, and 6 months, with a focus on Attention/Vigilance. Exercise was measured by the International Physical Activity Questionnaire and the number of exercise sessions completed. Attention/Vigilance was differentially enhanced by cognitive training and physical exercise compared to cognitive training and healthy living group (T score gain of 4.6 vs. -0.2 over 6 months, P < .01). Improvement in Attention/Vigilance by 3 months was significantly associated with number of exercise sessions attended (P = .02) and exercise intensity (P < .03) during that period. Attention/Vigilance gain by 6 months was significantly predicted by total metabolic energy expended during the first 3 months (P = .04) and proportion of group exercise sessions attended (P < .01) over 6 months. In the first 3 months, brain-derived neurotropic factor tended to increase in the exercise condition but decrease in the comparison condition. Adding an exercise program to cognitive training enhances the impact on the core deficit in attention in schizophrenia. The gains in attention are significantly related to the amount and intensity of exercise, consistent with the view that physical exercise is driving the attention improvements beyond the effect of cognitive training.
Electroencephalographic (EEG) or magnetoencephalographic (MEG) microstates, ie, discrete spatial configurations of brain signals over time, are thought to reflect the activity of large-scale brain circuits. Altered EEG microstates associated with cognitive control and attention have been consistently reported in schizophrenia (SCZ). However, EEG microstate characterization in other psychiatric disorders and treatment-related modulations are still unclear. MEG microstates (mMSs) have only recently been explored and despite source detection advantages have not been applied to characterize psychiatric disorders so far. Controlling for the impact of treatment, we expected altered mMSs corresponding to brain sources associated with cognitive dysfunction in SCZ. We studied mMSs in a large cohort of controls and patients with SCZ, bipolar disorder (BD), and major depressive disorder (MDD). First, we assessed treatment-related modulations and, after removing treatment bias, we explored anomalies in psychiatric disorders and possible associations with psychopathology. Benzodiazepine administration was associated with reduced mMS variance and duration, together with increased occurrence across diagnoses. After excluding patients receiving benzodiazepines, patients with SCZ showed increased contribution of occipito-parietal (mMS 1-2) and reduced fronto-temporal and centro-parietal (mMS 3-4) configurations relative to controls. Altered mMSs reflected impairments in brain generators linked to sensory processing and cognitive function. Analyses in BD and MDD, featuring smaller sample sizes, showed no significant differences from controls. In summary, we detected mMSs disruptions in patients with SCZ, involving source brain regions associated with sensory integration and cognition. These effects did not depend on pharmacological treatment and were not significant in mood disorders.
Improving Thinking through Everyday Self-Assessment Training combines 16 weeks of daily mobile task-based training in IA with weekly individual coaching in applying IA to everyday behaviors. Sixty individuals with diagnoses of schizophrenia or schizoaffective disorder participated in an open trial of iTEST with assessments at baseline, 8, 12, and 16 weeks. Primary outcomes included IA on 2 trained tasks (mobile verbal learning and facial emotion recognition tests) and 3 untrained tasks (verbal memory, emotion recognition, and executive functioning). Improving Thinking through Everyday Self-Assessment Training showed strong feasibility, retaining 86.7% of participants, and strong adherence with an average daily mobile-training completion rate of 87%. In linear-mixed models with intent-to-treat data, statistically significant IA improvements were observed over time in both trained tasks and in 2 of the 3 untrained tasks (Cohen's d's = 0.5-1.28). Significant improvements were also observed in secondary outcomes of real-world function, positive symptoms, and depression. This project provides the first data, to our knowledge, to demonstrate that IA in schizophrenia can be improved. Improving Thinking through Everyday Self-Assessment Training also represents one of just a few blended digital health interventions, including remote cognitive training, and may therefore serve as a blueprint for future intervention development.
Cognitive models of schizophrenia-spectrum disorders (SSD) posit dysfunctional beliefs and cognitive biases as maintenance mechanisms of positive and negative symptoms. Although cognitive behavioral therapy (CBT) targets these processes, its effects on mechanism-level outcomes remain unclear. This review examined whether CBT modifies dysfunctional beliefs and cognitive biases in SSD using rigorous randomized evidence. PRISMA 2020-compliant systematic review and meta-analysis (PROSPERO registered). Primary analyses were restricted to intention-to-treat (ITT) randomized controlled trials (RCTs) in SSD samples, using random-effects models and between-group post-treatment estimates. Pre-post and nonrandomized studies were analyzed separately as secondary evidence. Subgroup and meta-regression analyses were conducted. Thirty-three studies met inclusion criteria. Fourteen ITT RCTs contributed to the primary pooled analysis of dysfunctional beliefs, yielding a small but statistically significant effect favoring CBT (g = 0.154, 95% CI, 0.049-0.259). Effects were strongest for delusional conviction (g = 0.450) and self-related schemas (positive-self g = 0.278; negative-self g = 0.298). Voice-related beliefs did not reach statistical significance. Too few RCTs assessed cognitive biases to support primary pooled analyses; exploratory findings suggested small effects for belief inflexibility and no reliable effect for jumping-to-conclusions. Greater reductions in dysfunctional beliefs were associated with greater improvements in positive symptoms across trials. CBT produces small but reliable improvements in dysfunctional beliefs in SSD, although effects vary by domains particularly for delusional conviction and self-schemas, supporting their role as modifiable therapeutic targets and plausible mechanisms of change. Effects on cognitive biases remain limited and understudied.
The requirement for hospital admission to initiate clozapine presents a health-systems-related barrier to clozapine prescription and contributes to its underutilization in treatment-resistant schizophrenia (TRS). This study aimed to examine the clinicodemographic characteristics associated with treatment settings for clozapine initiation within a first-episode psychosis (FEP) cohort attending an early intervention in psychosis service. Secondary analysis of a retrospective cohort study of 1220 young people presenting with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne between 2011 - 2017. Ninety-one cases of TRS were identified and included in the analysis, with 70 commencing clozapine, of whom 67 had a commencement setting identified. Over half (n = 36, 53.7%) commenced clozapine in the community. When compared to the hospital initiation group, the community initiation group were less likely to have had a hospital admission at baseline (odds ratio (OR) 0.26, 95%CI, 0.09-0.87) or an involuntary admission during the 2 year episode of care with EPPIC (OR 0.25, 95%CI, 0.09-0.70). The community initiated group had presented with less severe delusion scores on short form Scale for Assessment of Positive Symptoms at baseline (mean 3.08 vs 3.94, P = .031). First generation migrants were less likely to initiate clozapine in the community (OR 0.29, 95%CI, 0.09-0.97). The community initiation group also had reduced odds of clozapine discontinuation until discharge from EPPIC (OR 0.22, 95%CI, 0.06-0.76). Community initiation provides an alternative route to clozapine treatment and may be associated with a reduced rate of clozapine discontinuation.
Impairments in interpersonal functioning are common across bipolar disorder (BD) and schizophrenia (SZ). Social competence and social cognition predict impairments in interpersonal functioning in participants with SZ, but the importance of negative symptoms and impairments in self-assessment of social cognition is also substantial. We expanded our previous research to include participants with BD and broadened the range of predictors to examine the importance of different predictors of interpersonal functioning. Participants with BD (n = 114) and SZ (n = 126) were evaluated. Interpersonal functioning was examined with observer ratings using the Specific Level of Functioning (SLOF). Predictors included performance-based measures of social competence, observer ratings and performance-based assessments of neurocognition and social cognition, clinically rated negative symptoms and depression, self-assessments of neurocognitive and social cognitive abilities, and data on moods, location, activities, and social context collected in a 30-day Ecological Momentary Assessment period. Negative symptoms were the best predictor of interpersonal functioning in both SZ and BD. In both groups, social competence and observer ratings of social cognition accounted for variance in interpersonal functioning, and depression was a significantly stronger predictor of interpersonal functioning in BD. Negative symptoms are strongly related to interpersonal functioning, but the pattern of correlations suggests that social cognition and social competence are likely to be important treatment targets across diagnoses. The lack of previous research on social competence in BD is under-scored by these results, with social skills training possibly having promise and a greater chance of success in BD.
In this review, we highlight Barbara Cornblatt's transformative contributions to the study and understanding of attention in psychosis. We begin by summarizing Cornblatt's work on attention starting in the late 1970s, including her work showing that impaired vigilance is a heritable risk factor and predictor of psychosis, and her key role in the creation of the gold-standard Continuous Performance Test-Identical Pairs. We then summarize major developments in the understanding of attention in psychosis since that time, all of which have been influenced by the work and insights of Cornblatt. Finally, we describe recent research in this area and discuss ways that emerging ideas and methods could transform attention research going forward, building upon Cornblatt's foundational work.
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