Schizophrenia Bulletin最新文献

Background and hypothesis: Despite the clinical relevance of negative symptoms in schizophrenia, our understanding of negative symptoms remains limited. Although various courses and stages of schizophrenia have been identified, variations in the negative symptom networks between distinct stages of schizophrenia remain unexplored.

Study design: We examined 405 patients with early schizophrenia (ES) and 330 patients with chronic schizophrenia (CS) using the Scale for the Assessment of Negative Symptoms. Network analysis and exploratory graph analysis were used to identify and compare the network structures and community memberships of negative symptoms between the two groups. Further, associations between communities and social functioning were evaluated. The potential influences of other symptom domains and confounding factors were also examined.

Study results: Multidimensional differences were found in the networks of negative symptoms between ES and CS. The global connectivity strength was higher in the network of ES than in the network of CS. In ES, central symptoms were mainly related to expressive deficits, whereas in CS they were distributed across negative symptom domains. A three-community structure was suggested across stages but with different memberships and associations with social functioning. Potential confounding factors and symptom domains, including mood, positive, disorganization, and excitement symptoms, did not affect the network structures.

Conclusion: Our findings revealed the presence of stage-specific network structures of negative symptoms in schizophrenia, with negative symptom communities having differential significance for social functioning. These findings provide implications for the future development of tailored interventions to alleviate negative symptoms and improve functionality across stages.

Background: Cognitive impairment associated with schizophrenia (CIAS) negatively impacts daily functioning, quality of life, and recovery, yet effective pharmacotherapies and practical assessments for clinical practice are lacking. Despite the pivotal progress made with establishment of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for clinical research, implementation of the full MCCB is too time-consuming and cost-ineffective for most clinicians in clinical practice.

Study design: Here we discuss current assessments in relation to delivery format (interview-based and performance-based), validity, ease of use for clinicians and patients, reliability/reproducibility, cost-effectiveness, and suitability for clinical implementation. Key challenges and future opportunities for improving cognitive assessments are also presented.

Study results: Current assessments that require 30 min to complete would have value in clinical settings, but the associated staff training and time required might preclude their application in most clinical settings. Initial profiling of cognitive deficits may require about 30 min to assist in the selection of evidence-based treatments; follow-up monitoring with brief assessments (10-15 min in duration) to detect treatment-related effects on global cognition may complement this approach. Guidance on validated brief cognitive tests for the strategic monitoring of treatment effects on CIAS is necessary.

Conclusions: With increased advancements in technology-based and remote assessments, development of validated formats of remote and in-person assessment, and the necessary training models and infrastructure required for implementation, are likely to be of increasing clinical relevance for future clinical practice.

Background and hypothesis: Nonpsychotic symptoms (depression, anxiety, obsessions, etc.) are frequent in schizophrenia-spectrum disorders and are usually conceptualized as comorbidity or transdiagnostic symptoms. However, in twentieth century foundational psychopathological literature, many nonpsychotic symptoms with specific phenomenology (here termed pseudoneurotic symptoms) were considered relatively typical of schizophrenia. In this prospective study, we investigated potential associations of pseudoneurotic symptoms with diagnostic status, functional outcome as well as psychopathological dimensions of schizophrenia.

Study design: First-admitted patients (N = 121) diagnosed with non-affective psychosis, schizotypal disorder, or other mental illness were examined at initial hospitalization and 5 years later with a comprehensive assessment of psychopathology. Informed by the literature, we constructed scales targeting pseudoneurotic symptoms and other, more general, nonpsychotic symptoms.

Study results: Pseudoneurotic symptoms aggregated in schizophrenia-spectrum groups compared to other mental illnesses and occurred at similar levels at baseline and follow-up. They longitudinally predicted poorer social and occupational functioning in schizophrenia-spectrum patients over a 5-year-period but not transition to schizophrenia-spectrum disorders from other mental illnesses. Finally, the level of pseudoneurotic symptoms correlated with disorder of basic self at both assessments and with positive and negative symptoms at follow-up. The scale targeting general nonpsychotic symptoms did not show this pattern of associations.

Conclusions: The study supports that a group of nonpsychotic symptoms, ie, pseudoneurotic symptoms, are associated with schizophrenia-spectrum disorders and linked with temporally stable psychopathology, particularly disorder of the basic self. Their prospective association with social and occupational functioning needs replication.

Background and hypothesis: Negative symptoms are very important for the overall loss of functioning observed in patients with schizophrenia. There is a need for valid tools to assess these symptoms.

Study design: We used the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) systematic review guideline to evaluate the quality of the clinical assessment interview for negative symptoms (CAINS) as a clinician-rated outcome measurement (ClinROM).

Study results: The search strategy resulted in the retrieval of 13 articles, 11 of which were included in this evaluation. In terms of risk of bias, most articles reported on measures of internal consistency and construct validity, which were overall of good quality. Structural validity, reliability, measurement error, and cross-cultural validity were reported with less than optimum quality. There was a risk of bias in ClinROM development. According to the updated criteria of good measurement properties, structural validity, internal consistency, and reliability showed good results. In contrast, hypothesis testing was somewhat poorer. Results for cross-cultural validity were indeterminate. According to the updated GRADE approach from the COSMIN group the scale received a moderate grade.

Conclusions: The COSMIN standard allows a judgment of the CAINS as an instrument with the potential to be recommended for use, but which requires further research to assess its quality, in particular in the domains of content validity, internal consistency, and cross-cultural validity.

Background and hypothesis: This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques.

Study design: This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA.

Study results: Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients.

Conclusions: Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.

Background and hypothesis: Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our understanding of illness trajectories preceding FEP, we aimed to investigate combinations and temporal associations among precursor symptoms.

Study design: Participants were from PEPP-Montréal, a catchment-based early intervention program for FEP. Through semistructured interviews, collateral from relatives, and a review of health and social records, we retrospectively measured the presence or absence of 29 precursor symptoms, including 9 subthreshold psychotic and 20 nonpsychotic symptoms. Sequences of symptoms were derived from the timing of the first precursor symptom relative to the onset of FEP.

Study results: The sample included 390 participants (68% men; age range: 14-35 years). Combinations of precursor symptoms most frequently featured depression, anxiety, and substance use. Of 256 possible pairs of initial and subsequent precursor symptoms, many had asymmetrical associations: eg, when the first symptom was suspiciousness, the incidence rate ratio (IRR) of subsequent anxiety was 3.40 (95% confidence interval [CI]: 1.79, 6.46), but when the first symptom was anxiety, the IRR of subsequent suspiciousness was 1.15 (95% CI: 0.77, 1.73).

Conclusions: A detailed examination of precursor symptoms reveals diverse clinical profiles that cut across diagnostic categories and evolve longitudinally prior to FEP. Their identification may contribute to risk assessments and provide insights into the mechanisms of illness progression.

Background and hypothesis: The brain-predicted age difference (brain-PAD) may serve as a biomarker for neurodegeneration. We investigated the brain-PAD in patients with schizophrenia (SCZ), first-episode schizophrenia spectrum disorders (FE-SSDs), and treatment-resistant schizophrenia (TRS) using structural magnetic resonance imaging (sMRI).

Study design: We employed a convolutional network-based regression (SFCNR), and compared its performance with models based on three machine learning (ML) algorithms. We pretrained the SFCNR with sMRI data of 7590 healthy controls (HCs) selected from the UK Biobank. The parameters of the pretrained model were transferred to the next training phase with a new set of HCs (n = 541). The brain-PAD was analyzed in independent HCs (n = 209) and patients (n = 233). Correlations between the brain-PAD and clinical measures were investigated.

Study results: The SFCNR model outperformed three commonly used ML models. Advanced brain aging was observed in patients with SCZ, FE-SSDs, and TRS compared to HCs. A significant difference in brain-PAD was observed between FE-SSDs and TRS with ridge regression but not with the SFCNR model. Chlorpromazine equivalent dose and cognitive function were correlated with the brain-PAD in SCZ and FE-SSDs.

Conclusions: Our findings indicate that there is advanced brain aging in patients with SCZ and higher brain-PAD in SCZ can be used as a surrogate marker for cognitive dysfunction. These findings warrant further investigations on the causes of advanced brain age in SCZ. In addition, possible psychosocial and pharmacological interventions targeting brain health should be considered in early-stage SCZ patients with advanced brain age.

Background: Most people with psychotic disorders will never commit an act of violence. However, the risk of violence committed by people with schizophrenia is higher than the general population. Violence risk is also known to be highest during the first episode of psychosis compared to later stages of illness. Despite this, there have been no comprehensive reviews conducted in the past 10 years examining rates of violence during FEP. We aimed to provide an updated review of the rate of violence in people with FEP.

Study design: Meta-analytical techniques were used to identify pooled proportions of violence according to severity (less serious, serious, severe) and timing of violence (before presentation, at first presentation, after presentation to services).

Study results: Twenty-two studies were included. The pooled prevalence was 13.4% (95% CI [9.0%-19.5%]) for any violence, 16.3% (95% CI [9.1%-27.4%]) for less serious violence, 9.7% (95% CI [5.4%-17.0%]) for serious violence and 2.7% for severe violence, regardless of time point. The pooled prevalence of any violence was 11.6% (95% CI [6.8%-18.9%]) before presentation, 20.8% (95% CI [9.8%-38.7%]) at first presentation and 13.3% (95% CI [7.3%-23.0%]) after presentation to services.

Conclusion: Overall, rates of violence appear to be lower in more recent years. However, due to the high between-study heterogeneity related to study design, the findings must be interpreted with consideration of sample characteristics and other contextual factors. The prevalence of violence remained high at all-time points, suggesting that more targeted, holistic, and early interventions are needed for clinical FEP groups.