The latest medical research on Schizophrenia
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Request AccessInternational Experience of Implementing Cognitive Remediation for People With Psychotic Disorders.
Schizophrenia BulletinCognitive remediation (CR) is an effective therapy for the cognitive impact of mental illness, especially schizophrenia. Global efforts are being made to implement CR into routine mental health services with the aim of improving functional outcomes for the population of people recovering from mental illness. Implementation and dissemination of CR in heterogeneous settings require knowledge gleaned from formal implementation research and pragmatic experiential learning. This article describes cross-cultural approaches to CR implementation, focusing on initiatives in France, the United States, Australia, and Japan.
Key leaders in the implementation of CR in France, the United States, Australia, and Japan were asked to describe the implementation and dissemination process in their settings with respect to the categories of context, implementation, outcomes, facilitators, and barriers.
All 4 sites noted the role of collaboration to leverage the implementation of CR into mental health rehabilitation services. In France, high-level, government organizational backing enhanced the dissemination of CR. Academic and clinical service partnerships in the United States facilitated the dissemination of programs. The advocacy from service users, families, and carers can aid implementation. The support from international experts in the field can assist in initiating programs but maintenance and dissemination require ongoing training and supervision of staff.
CR is an effective intervention for the cognitive impact of schizophrenia. Programs can be implemented in diverse settings globally. Adaptations of CR centering upon the core components of effective CR therapy enhance outcomes and enable programs to integrate into diverse settings.
Exploring Schizophrenia Classification Through Multimodal MRI and Deep Graph Neural Networks: Unveiling Brain Region-Specific Weight Discrepancies and Their Association With Cell-Type Specific Transcriptomic Features.
Schizophrenia BulletinSchizophrenia (SZ) is a prevalent mental disorder that imposes significant health burdens. Diagnostic accuracy remains challenging due to clinical subjectivity. To address this issue, we explore magnetic resonance imaging (MRI) as a tool to enhance SZ diagnosis and provide objective references and biomarkers. Using deep learning with graph convolution, we represent MRI data as graphs, aligning with brain structure, and improving feature extraction, and classification. Integration of multiple modalities is expected to enhance classification.
Our study enrolled 683 SZ patients and 606 healthy controls from 7 hospitals, collecting structural MRI and functional MRI data. Both data types were represented as graphs, processed by 2 graph attention networks, and fused for classification. Grad-CAM with graph convolution ensured interpretability, and partial least squares analyzed gene expression in brain regions.
Our method excelled in the classification task, achieving 83.32% accuracy, 83.41% sensitivity, and 83.20% specificity in 10-fold cross-validation, surpassing traditional methods. And our multimodal approach outperformed unimodal methods. Grad-CAM identified potential brain biomarkers consistent with gene analysis and prior research.
Our study demonstrates the effectiveness of deep learning with graph attention networks, surpassing previous SZ diagnostic methods. Multimodal MRI's superiority over unimodal MRI confirms our initial hypothesis. Identifying potential brain biomarkers alongside gene biomarkers holds promise for advancing objective SZ diagnosis and research in SZ.
Evaluation of the Glymphatic System in Schizophrenia Spectrum Disorder Using Proton Magnetic Resonance Spectroscopy Measurement of Brain Macromolecule and Diffusion Tensor Image Analysis Along the Perivascular Space Index.
Schizophrenia BulletinThe glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index.
Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity.
MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01).
Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD.
Physical Activity, Sleep, and Risk of Late-Onset Severe Mental Illness: A Prospective Cohort Study From UK Biobank.
Schizophrenia BulletinPrevious studies have found that both physical inactivity and poor sleep are deleteriously associated with severe mental illness (SMI). The aim of current study was to investigate the joint association of physical activity (PA) and sleep with late-onset SMI (schizophrenia and bipolar disorder) risk.
A total of 340 187 (for schizophrenia)/340 239 (for bipolar disorder) participants without schizophrenia or bipolar disorder from the UK Biobank were included. Baseline PA levels were categorized as high, intermediate, and low according to the total volume of PA. Sleep was categorized into healthy, intermediate, and poor according to an established composited sleep score of chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. We derived 9 PA-sleep combinations, accordingly.
After an average follow-up of 13.2 years, 814 participants experienced schizophrenia and 846 participants experienced bipolar disorder. Both low PA level, intermediate, and poor sleep were independently associated with increased risk of SMI. PA level and sleep had additive and multiplicative interactions on SMI risk. Compared to those with high PA level and healthy sleep, individuals with low PA and poor sleep had the highest risk of SMI (hazard ratio: 1.95; 95% CI: 1.02-3.70, P < .001) for schizophrenia; (hazard ratio: 3.81; 95% CI: 2.35-6.15) for bipolar disorder. A higher PA level may attenuate the detrimental effects of poor sleep.
Both low PA and poor sleep was associated with increasing risk of late-onset SMI. Those with low PA and poor sleep had the highest risk of late-onset SMI, suggesting likely synergistic effects. Our findings supported the need to target both PA and sleep behaviors in research and clinical practice.
Advancements and Future Directions in Prevention Based on Evaluation for Individuals With Clinical High Risk of Psychosis: Insights From the SHARP Study.
Schizophrenia BulletinThis review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals.
The review provides an overview of the developmental history of the SHARP study and its contributions to understanding the needs of CHR individuals. It explores the limitations of traditional antipsychotic approaches and introduces PBE as a promising framework for intervention.
Three key interventions implemented by the SHARP team are discussed: nutritional supplementation based on niacin skin response blunting, precision transcranial magnetic stimulation targeting cognitive and brain functional abnormalities, and cognitive behavioral therapy for psychotic symptoms addressing symptomatology and impaired insight characteristics. Each intervention is evaluated within the context of PBE, emphasizing the potential for tailored approaches to CHR individuals.
The review highlights the strengths and clinical applications of the discussed interventions, underscoring their potential to revolutionize preventive care for CHR individuals. It also provides insights into future directions for PBE in CHR populations, including efforts to expand evaluation techniques and enhance precision in interventions.
A Developmental Perspective on Early and Current Motor Abnormalities and Psychotic-Like Symptoms.
Schizophrenia BulletinPsychotic-like experiences (PLEs) are prevalent in the general population and, because they represent a lower end of the psychosis vulnerability spectrum, may be useful in informing mechanistic understanding. Although it is well-understood that motor signs characterize formal psychotic disorders, the developmental trajectory of these features and their relationships with PLEs are less well-understood.
Data from 7559 adolescents and young adults (age 11-21) in the Philadelphia Neurodevelopmental Cohort were used to investigate whether early-life milestone-attainment delays relate to current adolescent sensorimotor functioning and positive and negative PLEs. Current sensorimotor functioning was assessed using the Computerized Finger Tapping task (assessing motor slowing) and Mouse Practice task (assessing sensorimotor planning).
Early developmental abnormalities were related to current adolescent-aged motor slowing (t(7415.3) = -7.74, corrected-P < .001) and impaired sensorimotor planning (t(7502.5) = 5.57, corrected-P < .001). There was a significant interaction between developmental delays and current sensorimotor functioning on positive and negative PLEs (t = 1.67-4.51), such that individuals with early developmental delays had a stronger positive relationship between sensorimotor dysfunction and PLEs. Importantly, interaction models were significantly better at explaining current PLEs than those treating early and current sensorimotor dysfunction independently (χ2 = 4.89-20.34).
These findings suggest a relationship between early developmental delays and current sensorimotor functioning in psychosis proneness and inform an understanding of heterotypic continuity as well as a neurodevelopmental perspective of motor circuits. Furthermore, results indicate that motor signs are a clear factor in the psychosis continuum, suggesting that they may represent a core feature of psychosis vulnerability.
The Complex Latent Structure of Attenuated Psychotic Symptoms: Hierarchical and Bifactor Models of SIPS Symptoms Replicated in Two Large Samples at Clinical High Risk for Psychosis.
Schizophrenia BulletinThe Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms.
Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043). Criterion validity was tested through relationships with CHR status, comorbid symptoms/diagnoses, functional impairment, demographics, neurocognition, and conversion to psychotic disorders.
Most variance in SIPS items (75%-77%) was attributable to a general factor. Hierarchical and bifactor models included a general factor and five specific/lower-order factors (positive symptoms, eccentricity, avolition, lack of emotion, and deteriorated thought process). CHR participants were elevated on the general factor and the positive symptoms factor. The general factor was associated with depressive symptoms; functional impairment; and mood, anxiety, and schizotypal personality diagnoses. The general factor was the best predictor of psychotic disorders (d ≥ 0.50). Positive symptoms and eccentricity had specific effects on conversion outcomes. The deteriorated thought process was least meaningful/replicable.
Attenuated psychotic symptoms, measured by the SIPS, have a complex hierarchical structure with a strong general factor. The general factor relates to internalizing symptoms and functional impairment, emphasizing the roles of general psychopathological distress/impairment in psychosis risk. Shared symptom variance complicates the interpretation of raw symptom scores. Broad transdiagnostic assessment is warranted to model psychosis risk accurately.
Validation of an ICD-Code-Based Case Definition for Psychotic Illness Across Three Health Systems.
Schizophrenia BulletinPsychosis-associated diagnostic codes are increasingly being utilized as case definitions for electronic health record (EHR)-based algorithms to predict and detect psychosis. However, data on the validity of psychosis-related diagnostic codes is limited. We evaluated the positive predictive value (PPV) of International Classification of Diseases (ICD) codes for psychosis.
Using EHRs at 3 health systems, ICD codes comprising primary psychotic disorders and mood disorders with psychosis were grouped into 5 higher-order groups. 1133 records were sampled for chart review using the full EHR. PPVs (the probability of chart-confirmed psychosis given ICD psychosis codes) were calculated across multiple treatment settings.
PPVs across all diagnostic groups and hospital systems exceeded 70%: Mass General Brigham 0.72 [95% CI 0.68-0.77], Boston Children's Hospital 0.80 [0.75-0.84], and Boston Medical Center 0.83 [0.79-0.86]. Schizoaffective disorder PPVs were consistently the highest across sites (0.80-0.92) and major depressive disorder with psychosis were the most variable (0.57-0.79). To determine if the first documented code captured first-episode psychosis (FEP), we excluded cases with prior chart evidence of a diagnosis of or treatment for a psychotic illness, yielding substantially lower PPVs (0.08-0.62).
We found that the first documented psychosis diagnostic code accurately captured true episodes of psychosis but was a poor index of FEP. These data have important implications for the case definitions used in the development of risk prediction models designed to predict or detect undiagnosed psychosis.
Positive Reframing of Psychosis Risk Is Seen as More Beneficial and Less Harmful Than Negative Framing by Clinicians: An Experimental Videotaped Simulated Feedback Study.
Schizophrenia BulletinRecent studies show that, despite providing some relief, feedback about being at risk for psychosis often triggers negative emotional reactions. Inspired by Tversky and Kahneman's (1981) work on the framing effect and medical framings that favors positive framing like "life-threatening" over "high-risk for death," this study tested the hypothesis that positive reframing of psychosis risk (PR) could alleviate these concerns. To establish the justifiability and feasibility of testing this hypothesis with patients and their families, the study first sought to test whether mental health professionals (MHPs) view positive framing as superior to present state-of-the-art approaches.
The study used an experimental design utilizing a simulated feedback session, recorded with professional actors, featuring a clinician, an adolescent, and his mother. One hundred forty-eight MHPs were randomly assigned to view either negatively or positively framed feedback and were asked about its induced impact on the adolescent and mother.
The study results supported our main hypothesis, indicating significant benefits of positive framing over negative in areas like empathy, stress reduction, stigma, help-seeking, and hope. Contrary to our second hypothesis, familiarity with PR did not affect these results.
These findings suggest that MHPs view positive reframing of PR as more beneficial and less harmful than present negative framing approaches. This sets the stage for subsequent phases that will assess the perceptions and preferences of individuals at risk and their families. The discussion highlights possible misconceptions of positive framing, such as labeling, positive psychology, and de-medicalization.
Towards the DSM-6: Results of a Survey of Experts on the Reintroduction of First-Rank Symptoms as Core Criteria of Schizophrenia and on Redefining Hallucinations.
Schizophrenia BulletinDiagnostic criteria for mental disorders are subject to change. This is particularly true for schizophrenia, whose diagnostic criteria in the current DSM-5 bear little resemblance to what Kraepelin once named "dementia praecox" and Bleuler termed "the schizophrenias." The present study reports results from a survey of experts on two core topics of schizophrenia: (a) whether subsequent editions of the DSM should once again give the Schneiderian first-rank symptoms (FRS; eg, thought broadcasting) the prominent role they had in the DSM-IV and (b) whether the currently quite narrow definition of hallucinations in the DSM-5 requiring them to be vivid and clear and have the full force and impact of normal perceptions should be broadened to incorporate perceptual-like phenomena that the individual can differentiate from proper perceptions but still perceives as real and externally generated.
The aim of the survey was to learn about experts' opinions with no clear hypotheses.
International experts on schizophrenia were recruited via various sources and invited to participate in a short online survey. The final sample comprised 136 experts with a subgroup of 53 experts with verified identity and at least 6 years of clinical and/or research experience.
Slightly more experts voted in favor (49.3%) of returning FRS to the prominent role they had in earlier versions of the DSM than against (34.6%). Approximately four out of five experts agreed that the definition of hallucinations in the DSM should be expanded. According to the results, alongside internal symptoms that are phenomenologically indistinguishable from true perceptions, sensory intrusions that the holder is convinced were inserted from another source (ie, not self-generated) should be included in the definition.
While a large majority of experts recommend a change in the definition of hallucinations, the experts' opinions on FRS are more mixed. We hope that this article will stimulate future studies targeting the diagnostic relevance of these symptoms and encourage discussion about the definition of core psychotic symptoms and the diagnostic criteria for the upcoming edition of the DSM.
Clozapine Efficacy and Adverse Drug Reactions Among a Nationwide Study of 1021 Australians Prescribed Clozapine: The ClozaGene Study.
Schizophrenia BulletinThe ClozaGene Study is a nationwide cohort of adults who have been treated with clozapine. While clozapine is indicated in the management of treatment-resistant schizophrenia, it is associated with a considerable adverse drug reaction (ADR) burden, and not all patients achieve adequate symptomatic response. The current study focuses on self-reported experiences of clozapine use and response, clozapine-associated ADRs, and mental health comorbidity.
A total of 1021 participants (41.0% female; aged 46.2 ± 10.6 years [range 18-66]) were recruited via a mail-out based on prescriptions for clozapine. Participants completed a self-report questionnaire.
Most participants (90.1%, n = 912) were living with schizophrenia while 41.5% reported a lifetime diagnosis of depression, 15.6% bipolar disorder, and 8.1% schizoaffective disorder. Clozapine was currently prescribed to 944 (92.5%) participants and 37.8% of these participants self-reported currently taking additional antipsychotic medication. Nearly 3 quarters of participants living with schizophrenia reported that clozapine helped control their schizophrenia symptoms moderately to very well. The most commonly reported ADRs were sialorrhea (80.3%), weight gain (71.0%), constipation (56.9%), and sedation (52.8%). The prevalence of clozapine cessation due to clozapine-induced myocarditis and neutropenia was 1% and 0.4%, respectively.
Our findings highlight the high rate of psychotic and metabolic symptoms and ADRs among adults prescribed clozapine in the general Australian population. Future genomic analyses will focus on identifying genetic variants influencing clozapine treatment response and side effects.
Age-Related Changes in Sleep and Its Implications for Cognitive Decline in Aging Persons With Schizophrenia: A Critical Review.
Schizophrenia BulletinCognitive impairment is a core feature of schizophrenia that worsens with aging and interferes with quality of life. Recent work identifies sleep as an actionable target to alleviate cognitive deficits. Cardinal non-rapid eye movement (NREM) sleep oscillations such as sleep spindles and slow oscillations are critical for cognition. People living with schizophrenia (PLWS) and their first-degree relatives have a specific reduction in sleep spindles and an abnormality in their temporal coordination with slow oscillations that predict impaired memory consolidation. While NREM oscillatory activity is reduced in typical aging, it is not known how further disruption in these oscillations contributes to cognitive decline in older PLWS. Another understudied risk factor for cognitive deficits among older PLWS is obstructive sleep apnea (OSA) which may contribute to cognitive decline.
We conducted a narrative review to examine the published literature on aging, OSA, and NREM sleep oscillations in PLWS.
Spindles are propagated via thalamocortical feedback loops, and this circuitry shows abnormal hyperconnectivity in schizophrenia as revealed by structural and functional MRI studies. While the risk and severity of OSA increase with age, older PLWS are particularly vulnerable to OSA-related cognitive deficits because OSA is often underdiagnosed and undertreated, and OSA adds further damage to the circuitry that generates NREM sleep oscillations.
We highlight the critical need to study NREM sleep in older PWLS and propose that identifying and treating OSA in older PLWS will provide an avenue to potentially mitigate and prevent cognitive decline.
