Schizophrenia Bulletin最新文献

Background and hypothesis: Effective psychosocial interventions help people with schizophrenia live full and productive lives, but these interventions are not available to most people with schizophrenia. To facilitate access, interventions must be adapted and tested for delivery in community practice settings. In this pragmatic effectiveness trial, Cognitive Behavioral Social Skills Training (CBSST) was modified and tested for delivery by Assertive Community Treatment (ACT) teams in community mental health settings.

Study design: Participants with schizophrenia or schizoaffective disorder (N = 178) were recruited from publicly funded ACT teams operating in community settings and randomized to receive ACT alone or ACT + CBSST. Functioning (primary outcome), CBSST skill learning, symptoms, and defeatist attitudes were assessed every 18 weeks after baseline for 18 months.

Study results: Significant treatment effects were not found for functioning or any other outcome. CBSST delivery was low, but CBSST skill learning improved significantly more in ACT + CBSST, and post hoc exploratory analyses showed that exposure to more CBSST sessions was associated with greater skill learning, which in turn was associated with greater improvement in experiential negative symptoms and ultimately functioning.

Conclusion: The effectiveness of CBSST when delivered by typical community ACT providers may have been compromised by low delivery. Greater delivery of CBSST sessions was associated with greater skill acquisition which improved outcomes. Adapting CBSST to fit into the ACT service delivery creates an opportunity to substantially increase the number of individuals with schizophrenia who could access interventions like CBSST, but implementation research is needed to identify factors to promote session delivery.

Trial registration: ClinicalTrials.gov NCT02254733.

Background: The etiology of schizophrenia involves both biological and environmental risk factors. Studying childhood trauma in disorders along the schizophrenia spectrum, including schizotypal personality disorder (SPD), can inform early risk and protective factors for psychosis. However, no study has directly compared childhood trauma between SPD and schizophrenia.

Study design: One hundred twenty-four participants (schizophrenia/schizoaffective disorder [SZ] n = 45, SPD n = 32, and healthy controls [HCs] n = 47) matched on age and gender were assessed for different types of childhood abuse and neglect as well as clinical symptoms. Kruskal-Wallis H-tests examined group differences in childhood trauma severity and logistic regression modeled childhood trauma types that were associated with an SZ vs SPD diagnosis.

Study results: SZ and SPD had greater severity than HC on total trauma score and all types of childhood trauma assessed (all P-values < .05). SZ and SPD only differed on childhood sexual abuse, which was greater in SZ (P = .039). Childhood sexual abuse (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.02-1.27, P = .02) and emotional abuse (OR = 0.82, 95% CI = 0.71-0.95, P = .01) were independent predictors of an SZ vs SPD diagnosis. Sensitivity analysis indicated that a cutoff at mild sexual abuse was significant in predicting SZ vs SPD when compared with none/minimal sexual abuse. In SZ, greater sexual abuse was associated with positive schizotypal traits and in SPD, greater emotional abuse was associated with depressive symptoms.

Conclusions: Findings suggest that childhood sexual and emotional abuse may be important factors that influence illness trajectory across the severity of disorders on schizophrenia spectrum. These findings have implications for understanding disease mechanisms and early prevention.

Objective: This study investigated the relationships between baseline peptide antigen-related IgG levels and 8-week antipsychotic drug (APD) treatment response rates and one-year treatment outcomes, as well as the relationships between changes in peptide antigen-related IgG levels and one-year treatment outcomes, in first-episode schizophrenia (FES) patients.

Methods: Sixteen peptide antigen-related IgGs from proteins encoded by schizophrenia-related genes were selected on the basis of several selection criteria from a 2022 genome-wide association study. Novel peptide antigen-related IgG levels were measured in drug-naïve FES patients at baseline (n = 155) and in plasma samples from 60 healthy controls (HCs). At the one-year follow-up, 57 patients completed both symptom and autoantibody assessments. Statistical analyses included t tests, Pearson correlation analysis, linear regression analysis, linear mixed-effects models, and simple slope analysis.

Results: Anti-MOB4 IgG and anti-PDIA3 IgG levels were significantly lower in drug-naïve FES patients compared to HCs and showed a negative correlation with baseline excitement factor scores. Baseline anti-EMB IgG levels were associated with the 8-week treatment response, whereas anti-MAD1L1 IgG levels were correlated with one-year outcomes in drug-naïve FES patients. The one-year trajectory of changes in anti-FURIN IgG, anti-MAPK3 IgG, and anti-ACTR1B IgG levels was related to remission.

Conclusion: This study revealed that patients with schizophrenia had autoimmune abnormalities, with different peptide antigen-related IgG being associated with short-term or long-term treatment efficacy, and that these antibody levels were regulated by APDs.

Background and hypothesis: Minor physical abnormalities (MPAs) are neurodevelopmental markers that can be traced to prenatal events and may be significant features of early-onset schizophrenia (EOS). Therefore, our study aimed to (1) find the primary and interaction effects of MPAs for EOS and (2) develop and validate the model for EOS based on explainable machine learning algorithms.

Study design: The study included 549 patients with schizophrenia (193 EOS and 356 AOS) and 420 healthy controls (HC) in southern Taiwan. For the feature selection, variable selection using random forests (varSelRF) and recursive feature elimination (RFE) were applied to identify the important variables of MPAs. We used different machine learning algorithms to build the prediction models based on the selected MPAs variables.

Study results: The results showed that the mouth anomalies are significant MPAs variables and have interaction effects with craniofacial MPAs variables for EOS. The prediction models using the selected MPAs variables performed better in discriminating EOS vs HC compared to AOS vs HC. The AUC values for distinguishing EOS vs HC were 0.85-0.93, AOS vs HC were 0.80-0.87, and EOS vs AOS were 0.67-0.77 in validation sets.

Conclusions: This risk prediction model provides a clinical decision support system for detecting patients at high risk of developing EOS and enables early intervention in clinical practice.

Background and hypothesis: The pathogenesis of tardive dyskinesia (TD) remains unclear, involving multiple biological pathways. This study aimed to explore biomarkers of TD through untargeted metabolomics for the early identification of TD.

Study design: This study recruited 84 schizophrenia (SZ) patients with TD and 160 SZ patients without TD. TD diagnosis was based on the Schooler-Kane criteria, and the severity of TD and psychiatric symptoms were assessed using the Abnormal Involuntary Movement Scale and the Positive and Negative Syndrome Scale. Fasting blood samples were collected from all patients and subjected to untargeted metabolomics analysis using Ultra-high-performance liquid chromatography-high resolution mass spectrometry, allowing for the quantification and profiling of 699 metabolites. Data were analyzed with orthogonal partial least squares discriminant analysis, and receiver-operating characteristic curves.

Study results: In TD, 57 metabolites exhibited significant changes (variable importance of projection > 1, false discovery rate-adjusted P < .05), primarily involving amino acids and lipids. These changes predominantly affected the phenylalanine, tyrosine, and tryptophan pathway (impact = 0.5, P = .0252), as well as the phenylalanine metabolism pathway (impact = 0.36, P = .0498). N-Acetyl-l-phenylalanine (B = 2.249, t = 4.56, P < .001, 95% CI, 1.302-3.286) and Succinylcarnitine (AcCa(4:0-DC)) (B = 1.009, t = 3.07, P = .002, 95% CI, 0.362-1.656) are negatively related to the total abnormal involuntary movement scale score. Additionally, 5 differential metabolites had area under the curve (AUC) values greater than 0.7 for diagnosing TD, with the combined diagnostic capability exceeding 0.8 (AUC = 0.817, 95% CI, 0.759-0.875).

Conclusions: In TD, disruptions in amino acid and lipid metabolism were predominantly observed. Amino acids and lipid metabolites may be involved in the development of TD. Additionally, a biomarker panel composed of amino acids and lipids can be used for the differential diagnosis of TD.

Background and hypothesis: Individuals with schizophrenia (SZ) and bipolar disorder (BD) show disruptions in self-referential gaze perception-a social perceptual process related to symptoms and functioning. However, our current mechanistic understanding of these dysfunctions and relationships is imprecise.

Study design: The present study used mathematical modeling to uncover cognitive processes driving gaze perception abnormalities in SZ and BD, and how they relate to cognition, symptoms, and social functioning. We modeled the behavior of 28 SZ, 38 BD, and 34 controls (HC) in a self-referential gaze perception task using drift-diffusion models parameterized to index key cognitive components: drift rate (evidence accumulation efficiency), drift bias (perceptual bias), start point (expectation bias), threshold separation (response caution), and nondecision time (encoding/motor processes).

Study results: Results revealed that aberrant gaze perception in SZ and BD was driven by less efficient evidence accumulation, perceptual biases predisposing self-referential responses, and greater caution (SZ only). Across SZ and HC, poorer social functioning was related to greater expectation biases. Within SZ, perceptual and expectancy biases were associated with hallucination and delusion severity, respectively.

Conclusions: These findings indicate that diminished evidence accumulation and perceptual biases may underlie altered gaze perception in patients and that SZ may engage in compensatory cautiousness, sacrificing response speed to preserve accuracy. Moreover, biases at the belief and perceptual levels may relate to symptoms and functioning. Computational modeling can, therefore, be used to achieve a more nuanced, cognitive process-level understanding of the mechanisms of social cognitive difficulties, including gaze perception, in individuals with SZ and BD.

Background and hypothesis: Suicide rates among people with schizophrenia and other primary psychotic disorders are high, with the steepest increase in risk in the first years following contact with mental health services. Evidence suggests early intervention in psychosis services may reduce suicide risk for people experiencing first-episode psychosis. We aimed to compare the characteristics of patients with a recent (<12 month) onset of schizophrenia and other primary psychotic disorders with patients with a longer duration of illness (12 months and over) to identify key characteristics for patient suicide to aid services to effectively support patients during a particularly high-risk time.

Study design: A national clinical survey of patients with schizophrenia and other primary psychotic disorders who died by suicide in England and Wales between January 1, 2008 and December 31, 2021.

Study results: Of the 2828 (N = 18 487, 16%) patients with a diagnosis of schizophrenia and other primary psychotic disorders who died by suicide, ten percent (n = 288) were ill for less than 12 months. These patients were more often under the care of crisis teams or recently discharged from in-patient services than patients with a longer duration of illness (12 months and over), and they were more often seen by services within the week before they died. Patients with recent illness onset had fewer factors conventionally associated with suicide, such as alcohol or drug misuse, a history of violence, and self-harm. They were less likely to live alone and be unemployed.

Conclusions: Though all patients had contact with mental health services in the 12 months prior to death, patients with a recent onset of schizophrenia and other primary psychotic disorders were more commonly in recent contact with services at the time of death. They had fewer social and behavioral factors known to be common to suicide, suggesting lives recently disrupted by illness. Services should provide intensive support for patients who have been recently diagnosed, encouraging engagement and monitoring for deteriorating social factors.

Background and hypothesis: Schizophrenia (SCZ) is characterized by pervasive cognitive impairments and a high prevalence of lipid profile abnormalities. Emerging evidence suggests that these lipid profile disturbances may exacerbate cognitive decline, but the underlying neurophysiological mechanisms remain unclear. This study hypothesizes that SCZ patients with lipid profile abnormalities exhibit distinct cognitive deficits and electroencephalography (EEG) features, particularly in gamma-band activity, which may serve as potential biomarkers for cognitive dysfunction.

Study design: In this cross-sectional study, 137 SCZ patients were recruited, including 46 with lipid abnormalities and 91 with normal lipid profiles. Cognitive performance was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and symptom severity was evaluated via Positive and Negative Syndrome Scale. Resting-state EEG data were recorded and analyzed across 5 frequency bands (δ, θ, α, β, and γ).

Study results: Schizophrenia patients with lipid profile abnormalities showed significantly lower RBANS total and subdomain scores (especially in visuospatial/constructional ability, attention, and delayed memory). Electroencephalography analysis revealed reduced gamma-band power (30-48 Hz, 52-70 Hz) in these patients, which positively correlated with overall and domain-specific cognitive scores. Multiple regression analyses identified gamma-band power and education level as significant predictors of cognitive performance.

Conclusions: Lipid profile abnormalities in SCZ are associated with exacerbated cognitive impairment and attenuated gamma-band power. Gamma activity may reflect underlying synaptic and network dysfunction related to lipid dysregulation and serve as a promising noninvasive EEG biomarker for cognitive risk stratification in metabolically vulnerable SCZ subgroups.

Background and hypothesis: Schizo-obsessive comorbidity (SOC), defined as obsessive-compulsive symptoms (OCS) in schizophrenia (SCZ), is linked to severe psychopathology and poor prognosis. Schizophrenia and obsessive-compulsive disorder (OCD) share cognitive impairments, particularly in inhibition and cognitive flexibility, which may underlie SOC. However, little is known regarding the underlying neural mechanisms of SOC. We aimed to directly compare the inhibition- and cognitive flexibility-related neural activations between patients with SOC, SCZ, OCD, and healthy controls (HCs).

Study design: Twenty-eight patients with SOC, 33 SCZ patients, 30 OCD patients, and 33 HCs undertook fMRI while performing the combined shifting go/no-go task. We analyzed the shifting-related (shift vs go) and stopping-related (no-go vs go) activations among the different diagnostic groups.

Study results: Compared to HCs, the 3 clinical groups showed significant shifting-related hypoactivation in the left postcentral gyrus, left paracentral lobule, left supplementary motor area, and right superior frontal gyrus, with SOC exhibiting significantly lower activation than SCZ and OCD patients. Regarding stopping, OCD patients showed significant hyperactivation in the left precuneus compared with SCZ patients and HCs. Like OCD patients, SOC patients also exhibited greater hyperactivation than SCZ patients. Behaviorally, SOC and SCZ patients made significantly more commission errors than OCD patients, with SCZ also having more commission errors than HCs. Furthermore, SOC and SCZ made more shifting errors than HCs; and SOC made more shifting errors than SCZ and OCD patients.

Conclusions: All 3 clinical groups shared cognitive inflexibility. Moreover, the presence of the 2 features appears to amplify the neural alterations, implicating "additive effects."