Schizophrenia Bulletin最新文献

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 efficacy of yoga as an adjunctive treatment for schizophrenia spectrum disorders (SSD) has garnered interest. While yoga may positively influence various symptom domains, further investigation is needed due to the limited number, quality, and generalizability of studies. This study assessed the feasibility and acceptability (primary outcome) of a yoga-based group intervention (YoGI) developed in a participatory approach and explored its preliminary effectiveness.

Study design: In addition to the primary outcomes, this preregistered randomized controlled trial examined rater-blinded general psychopathology, positive- and negative symptoms, and self-rated depression, anxiety, stress, body mindfulness, mindfulness, psychological flexibility, cognition, social functioning, quality of life, and medication regime at baseline and postintervention as secondary outcomes.

Study results: Fifty inpatients with SSD received either TAU (n = 25) or YoGI + TAU (n = 25) for four weeks. Outcomes showed 95% protocol adherence of YoGI, feasibility, and retention rates of 91% and 94%, respectively, and a dropout rate of 6%. ANCOVA revealed significant between-group postintervention improvements for YoGI + TAU in positive symptoms, depression, cognitive fusion, and a mindfulness subscale. Medium-to-large pre- to postintervention effects were found for body mindfulness, positive, negative, and general psychopathology, cognitive fusion, depression, anxiety, stress, quality of life, and attention in YoGI + TAU, while within-group changes were consistently smaller in TAU. No severe adverse events were reported.

Conclusions: This trial supports the feasibility and acceptability of YoGI for inpatients with SSD and provides preliminary evidence of YoGI's benefits beyond TAU. Further robust, multicentric RCTs are warranted to deepen our understanding of YoGI's therapeutic potential and inform clinical interventions for SSD.

Background: A theory-driven cognitive therapy (Feeling Safe) has produced much better outcomes for patients with persecutory delusions. There are four distinct response classes: very high delusion conviction with large improvement, very high delusion conviction with no response, high delusion conviction with large improvement, and high delusion conviction with modest improvement. Our objective was to apply principal trajectories analysis, a novel statistical method, to original trial data to estimate whether these groups may have responded differently to a different intervention: befriending.

Design: One hundred and thirty patients with persistent persecutory delusions were randomised to six months of Feeling Safe or befriending. Baseline assessments were used to assign patients allocated to befriending (who did not receive Feeling Safe) into the four Feeling Safe response classes. The treatment effect, including on potential mediators, was then estimated for these classes.

Results: Patients in two treatment response classes (Very high conviction/large improvement, High conviction/large improvement) benefited more from Feeling Safe, patients in one group (Very high conviction/no improvement) benefited more from befriending, and patients in the remaining group (High conviction/moderate improvement) benefited equally from the interventions. Mechanism differences were detected when Feeling Safe was superior to befriending, but not when befriending was superior.

Conclusions: There may be patients with psychosis who benefit more from one type of therapy than another, likely due to different change mechanisms. The application of principal trajectories has generated testable hypotheses and a potential step toward personalised treatment. We recommend an investigation of whether sequential provision of the treatment types could enhance patient outcomes. Keywords: persecutory, delusions, outcome trajectories, psychosis, cognitive therapy.

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 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."