The latest medical research on Schizophrenia
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Request AccessDuration of Untreated Psychosis and Outcomes in First-Episode Psychosis: Systematic Review and Meta-analysis of Early Detection and Intervention Strategies.
Schizophrenia BulletinThe role of duration of untreated psychosis (DUP) as an early detection and intervention target to improve outcomes for individuals with first-episode psychosis is unknown.
PRISMA/MOOSE-compliant systematic review to identify studies until February 1, 2023, with an intervention and a control group, reporting DUP in both groups. Random effects meta-analysis to evaluate (1) differences in DUP in early detection/intervention services vs the control group, (2) the efficacy of early detection strategies regarding eight real-world outcomes at baseline (service entry), and (3) the efficacy of early intervention strategies on ten real-world outcomes at follow-up. We conducted quality assessment, heterogeneity, publication bias, and meta-regression analyses (PROSPERO: CRD42020163640).
From 6229 citations, 33 intervention studies were retrieved. The intervention group achieved a small DUP reduction (Hedges' g = 0.168, 95% CI = 0.055-0.283) vs the control group. The early detection group had better functioning levels (g = 0.281, 95% CI = 0.073-0.488) at baseline. Both groups did not differ regarding total psychopathology, admission rates, quality of life, positive/negative/depressive symptoms, and employment rates (P > .05). Early interventions improved quality of life (g = 0.600, 95% CI = 0.408-0.791), employment rates (g = 0.427, 95% CI = 0.135-0.718), negative symptoms (g = 0.417, 95% CI = 0.153-0.682), relapse rates (g = 0.364, 95% CI = 0.117-0.612), admissions rates (g = 0.335, 95% CI = 0.198-0.468), total psychopathology (g = 0.298, 95% CI = 0.014-0.582), depressive symptoms (g = 0.268, 95% CI = 0.008-0.528), and functioning (g = 0.180, 95% CI = 0.065-0.295) at follow-up but not positive symptoms or remission (P > .05).
Comparing interventions targeting DUP and control groups, the impact of early detection strategies on DUP and other correlates is limited. However, the impact of early intervention was significant regarding relevant outcomes, underscoring the importance of supporting early intervention services worldwide.
Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.
Schizophrenia BulletinThis article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the larges...
Childhood Adversity and Incident Psychotic Experiences in Early Adulthood: Cognitive and Psychopathological Mediators.
Schizophrenia BulletinChildhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood.
We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula.
In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results.
Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences.
Loneliness in the Daily Lives of People With Mood and Psychotic Disorders.
Schizophrenia BulletinLoneliness, the subjective experience of feeling alone, is associated with physical and psychological impairments. While there is an extensive literature linking loneliness to psychopathology, limited work has examined loneliness in daily life in those with serious mental illness. We hypothesized that trait and momentary loneliness would be transdiagnostic and relate to symptoms and measures of daily functioning.
The current study utilized ecological momentary assessment and passive sensing to examine loneliness in those with schizophrenia (N = 59), bipolar disorder (N = 61), unipolar depression (N = 60), remitted unipolar depression (N = 51), and nonclinical comparisons (N = 82) to examine relationships of both trait and momentary loneliness to symptoms and social functioning in daily life.
Findings suggest that both trait and momentary loneliness are higher in those with psychopathology (F(4,284) = 28.00, P < .001, ηp2 = 0.27), and that loneliness significantly relates to social functioning beyond negative symptoms and depression (β = -0.44, t = 6.40, P < .001). Furthermore, passive sensing measures showed that greater movement (β = -0.56, t = -3.29, P = .02) and phone calls (β = -0.22, t = 12.79, P = .04), but not text messaging, were specifically related to decreased loneliness in daily life. Individuals higher in trait loneliness show stronger relationships between momentary loneliness and social context and emotions in everyday life.
These findings provide further evidence pointing to the importance of loneliness transdiagnostically and its strong relation to social functioning. Furthermore, we show that passive sensing technology can be used to measure behaviors related to loneliness in daily life that may point to potential treatment implications or early detection markers of loneliness.
Understanding the Mechanisms of Cognitive Remediation on Recovery in People With Early Psychosis: A Mediation and Moderation Analysis.
Schizophrenia BulletinTo provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects.
We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path.
CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition.
Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration.
Elevations in the Mitochondrial Matrix Protein Cyclophilin D Correlate With Reduced Parvalbumin Expression in the Prefrontal Cortex of Patients With Schizophrenia.
Schizophrenia BulletinCognitive deficits in schizophrenia are linked to dysfunctions of the dorsolateral prefrontal cortex (DLPFC), including alterations in parvalbumin (PV)-expressing interneurons (PVIs). Redox dysregulation and oxidative stress may represent convergence points in the pathology of schizophrenia, causing dysfunction of GABAergic interneurons and loss of PV. Here, we show that the mitochondrial matrix protein cyclophilin D (CypD), a critical initiator of the mitochondrial permeability transition pore (mPTP) and modulator of the intracellular redox state, is altered in PVIs in schizophrenia.
Western blotting was used to measure CypD protein levels in postmortem DLPFC specimens of schizophrenic patients (n = 27) and matched comparison subjects with no known history of psychiatric or neurological disorders (n = 26). In a subset of this cohort, multilabel immunofluorescent confocal microscopy with unbiased stereological sampling methods were used to quantify (1) numbers of PVI across the cortical mantle (20 unaffected comparison, 14 schizophrenia) and (2) PV and CypD protein levels from PVIs in the cortical layers 2-4 (23 unaffected comparison, 18 schizophrenia).
In schizophrenic patients, the overall number of PVIs in the DLPFC was not significantly altered, but in individual PVIs of layers 2-4 PV protein levels decreased along a superficial-to-deep gradient when compared to unaffected comparison subjects. These laminar-specific PVI alterations were reciprocally linked to significant CypD elevations both in PVIs and total DLPFC gray matter.
Our findings support previously reported PVI anomalies in schizophrenia and suggest that CypD-mediated mPTP formation could be a potential contributor to PVI dysfunction in schizophrenia.
Systematic Review and Meta-analysis: Rates of Violence During First-Episode Psychosis (FEP).
Schizophrenia BulletinMost 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.
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).
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.
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.
Examining the Effectiveness of a Digital Media Campaign at Reducing the Duration of Untreated Psychosis in New York State: Results From a Stepped-wedge Randomized Controlled Trial.
Schizophrenia BulletinLonger duration of untreated psychosis (DUP) predicts worse outcomes in First Episode Psychosis (FEP). Searching online represents one of the first proactive step toward treatment initiation for many, yet few studies have informed how best to support FEP youth as they engage in early online help-seeking steps to care.
Using a stepped-wedge randomized design, this project evaluated the effectiveness of a digital marketing campaign at reducing DUP and raising rates of referrals to FEP services by proactively targeting and engaging prospective patients and their adult allies online.
Throughout the 18-month campaign, 41 372 individuals visited our website, and 371 advanced to remote clinical assessment (median age = 24.4), including 53 allies and 318 youth. Among those assessed (n = 371), 53 individuals (14.3%) reported symptoms consistent with psychotic spectrum disorders (62.2% female, mean age 20.7 years) including 39 (10.5%) reporting symptoms consistent with either Clinical High Risk (ie, attenuated psychotic symptoms; n = 26) or FEP (n = 13). Among those with either suspected CHR or FEP (n = 39), 20 (51.3%) successfully connected with care. The campaign did not result in significant differences in DUP.
This study highlights the potential to leverage digital media to help identify and engage youth with early psychosis online. However, despite its potential, online education and professional support alone are not yet sufficient to expedite treatment initiation and reduce DUP.
Clarifying Cognitive Control Deficits in Psychosis via Drift Diffusion Modeling and Attractor Dynamics.
Schizophrenia BulletinCognitive control deficits are prominent in individuals with psychotic psychopathology. Studies providing evidence for deficits in proactive control generally examine average performance and not variation across trials for individuals-potentially obscuring detection of essential contributors to cognitive control. Here, we leverage intertrial variability through drift-diffusion models (DDMs) aiming to identify key contributors to cognitive control deficits in psychosis.
People with psychosis (PwP; N = 122), their first-degree biological relatives (N = 78), and controls (N = 50) each completed 120 trials of the dot pattern expectancy (DPX) cognitive control task. We fit full hierarchical DDMs to response and reaction time (RT) data for individual trials and then used classification models to compare the DDM parameters with conventional measures of proactive and reactive control.
PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information. Both PwP and relatives showed protracted nondecision times to infrequent trial sequences suggesting slowed perceptual processing. Classification analyses indicated that DDM parameters differentiated between the groups better than conventional measures and identified drift rates during proactive control, nondecision time during reactive control, and cue bias as most important. DDM parameters were associated with real-world functioning and schizotypal traits.
Modeling of trial-level data revealed that slow evidence accumulation and longer preparatory periods are the strongest contributors to cognitive control deficits in psychotic psychopathology. This pattern of atypical responding during the DPX is consistent with shallow basins in attractor dynamic models that reflect difficulties in maintaining state representations, possibly mediated by excess neural excitation or poor connectivity.
Network Localization of State and Trait of Auditory Verbal Hallucinations in Schizophrenia.
Schizophrenia BulletinNeuroimaging studies investigating the neural substrates of auditory verbal hallucinations (AVH) in schizophrenia have yielded mixed results, which may be reconciled by network localization. We sought to examine whether AVH-state and AVH-trait brain alterations in schizophrenia localize to common or distinct networks.
We initially identified AVH-state and AVH-trait brain alterations in schizophrenia reported in 48 previous studies. By integrating these affected brain locations with large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we then leveraged novel functional connectivity network mapping to construct AVH-state and AVH-trait dysfunctional networks.
The neuroanatomically heterogeneous AVH-state and AVH-trait brain alterations in schizophrenia localized to distinct and specific networks. The AVH-state dysfunctional network comprised a broadly distributed set of brain regions mainly involving the auditory, salience, basal ganglia, language, and sensorimotor networks. Contrastingly, the AVH-trait dysfunctional network manifested as a pattern of circumscribed brain regions principally implicating the caudate and inferior frontal gyrus. Additionally, the AVH-state dysfunctional network aligned with the neuromodulation targets for effective treatment of AVH, indicating possible clinical relevance.
Apart from unifying the seemingly irreproducible neuroimaging results across prior AVH studies, our findings suggest different neural mechanisms underlying AVH state and trait in schizophrenia from a network perspective and more broadly may inform future neuromodulation treatment for AVH.
Systematic Review and Meta-analysis of Exercise Interventions for Psychotic Disorders: The Impact of Exercise Intensity, Mindfulness Components, and Other Moderators on Symptoms, Functioning, and Cardiometabolic Health.
Schizophrenia BulletinExercise therapy has been shown to be an effective complementary treatment for patients with psychotic disorders. However, the specific impacts of different training modalities remain poorly understood. This article aims to quantitatively review the moderating influence of different exercise modalities, hypothesizing that higher exercise intensity as well as utilization of mindfulness-based exercise (MBE) components, will improve intervention outcomes.
PubMed, Web of Science, and PsycINFO were searched from 2010 to March 2022 for randomized controlled trials investigating exercise interventions in patients with psychotic disorders (preregistration: https://doi.org/10.17605/OSF.IO/J8QNS). Outcomes considered were positive/negative symptoms, Positive and Negative Syndrome Scale (PANSS) General Psychopathology/Total scores, depressive symptoms, psychosocial functioning, quality of life, cardiorespiratory fitness, and body mass index. Separate meta-analyses, including moderator analyses, were performed to evaluate the moderating influence of different training modalities.
Of 6653 studies, 40 (n = 2111 patients) were included in the meta-analysis. The effects of moderate-intensity exercise exceed low-intensity approaches for PANSS Total scores (P = .02) and depressive symptoms (P = .04). The presence of MBE components was associated with improvements in positive symptoms (P = .04) and PANSS General Psychopathology subscores (P = .04) but also with higher error and between-study heterogeneity. Our analysis also shows improved intervention effects on depression in younger patients (P = .012) and improved psychosocial functioning scores following more frequent sessions (P < .01).
A minimum of moderate intensity should be considered. More frequent training sessions per week also seem to be beneficial. While adding mindfulness elements is promising, it increases heterogeneity and requires caution in terms of generalization.
"It's Tough to Be a Black Man with Schizophrenia": Randomized Controlled Trial of a Brief Video Intervention to Reduce Public Stigma.
Schizophrenia BulletinRacial discrimination and public stigma toward Black individuals living with schizophrenia create disparities in treatment-seeking and engagement. Brief, social-contact-based video interventions efficaciously reduce stigma. It remains unclear whether including racial identity experiences in video narrative yields greater stigma reduction. We hypothesized that we would replicate findings showing sustained stigma reduction in video-intervention groups vs control and that Black participants would show greater stigma reduction and emotional engagement than non-Black participants only for a racial-insights video presenting a Black protagonist.
Recruiting using a crowdsourcing platform, we randomized 1351 participants ages 18-30 to (a) brief video-based intervention, (b) racial-insights-focused brief video, or (c) non-intervention control, with baseline, post-intervention, and 30-day follow-up assessments. In 2-minute videos, a young Black protagonist described symptoms, personal struggles, and recovery from schizophrenia, with or without mentioning race-related experiences.
A 3 × 3 ANOVA showed a significant group-by-time interaction for total scores of each of five stigma-related domains: social distance, stereotyping, separateness, social restriction, and perceived recovery (all P < .001). Linear mixed modeling showed a greater reduction in stigma from baseline to post-intervention among Black than non-Black participants in the racial insights video group for the social distance and social restriction domains.
This randomized controlled trial replicated and expanded previous findings, showing the anti-stigma effects of a brief video tailored to race-related experiences. This underscores the importance of personalized, culturally relevant narratives, especially for marginalized groups who, more attuned to prejudice and discrimination, may particularly value identification and solidarity. Future studies should explore mediators/moderators to improve intervention efficacy.