Schizophrenia Bulletin最新文献

Background: Guidelines issued by professional organizations recommend that all patients with psychotic disorders who have had several psychotic relapses, continue maintenance anti-psychotic treatment. However, some patients discontinue anti-psychotics and do not later relapse. This study attempted to characterize those patients with psychotic disorders early in their disease not taking maintenance antipsychotics, who were not later hospitalized.

Study design: This population-based cohort study combined registry data on patients diagnosed in their first psychotic episode (ICD 10 code: F20-29) from Sweden (n = 20 848), and Israel (n = 10 045), and followed them for up to 7 years for re-hospitalization or death. Multivariate analyses assessed sociodemographic and clinical risk factors predicting rehospitalization or death in patients with one hospitalization and did not fill prescriptions for antipsychotics; results from Sweden and Israel were then meta-analyzed.

Study results: The main analysis of this paper included 1611 patients from Sweden and 1607 from Israel. Male gender (adjusted hazard ratio [aHR], 1.57; 95% confidence interval [CI], 1.16-2.13) and a diagnosis of narrowly defined schizophrenia (F20.0-F20.9; aHR, 1.85; 95% CI, 1.55-2.2) were associated with increased risk of a second hospitalization or death among those who did not use antipsychotics. No sociodemographic or clinical characteristics were associated with a decreased risk of a second hospitalization or death.

Conclusions: Based on registry data, it was not possible to characterize, in a clinically meaningful way, those patients who can safely discontinue anti-psychotic medications and not be re-hospitalized or die. Male gender and a diagnosis of narrowly defined schizophrenia were associated with an increased risk of later relapse.

Background: Evidence regarding schizophrenia relapse following acute electroconvulsive therapy (ECT) is sparse compared with that for depression, and we have no clear consensus on relapse proportions. We aimed to provide longitudinal information on schizophrenia relapse following acute ECT.

Study design: This systematic review and meta-analysis included randomised controlled trials (RCTs) and observational studies on post-acute ECT relapse and rehospitalization for schizophrenia and related disorders. For the primary outcome, we calculated the post-acute ECT pooled relapse estimates at each timepoint (3, 6, 12, and 24 months post-acute ECT) using a random effects model. For subgroup analyses, we investigated post-acute ECT relapse proportions by the type of maintenance therapy.

Study results: Among a total of 6413 records, 29 studies (3876 patients) met our inclusion criteria. The risk of bias was consistently low for all included RCTs (4 studies), although it ranged from low to high for observational studies (25 studies). Pooled estimates of relapse proportions among patients with schizophrenia responding to acute ECT were 24% (95% CI: 15-35), 37% (27-47), 41% (34-49), and 55% (40-69) at 3, 6, 12, and 24 months, respectively. When continuation/maintenance ECT was added to antipsychotics post-acute ECT, the 6-month relapse proportion was 20% (11-32).

Conclusion: Relapse occurred mostly within 6 months post-acute ECT for schizophrenia, particularly within the first 3 months. Relapse proportions plateaued after 6 months, although more than half of all patients could be expected to relapse within 2 years. Further high-quality research is needed to optimise post-acute ECT treatment strategies in patients with schizophrenia.

Background and hypothesis: Individuals with schizophrenia experience severe impairments in everyday functioning. Cognitive behavioral social skills training (CBSST) has demonstrated moderate effects on functional outcomes in controlled trials. This study examined whether CBSST, when integrated into assertive community treatment (ACT), improves daily-life functioning as assessed by ecological momentary assessment (EMA).

Study design: This was a secondary analysis of a pragmatic randomized controlled trial involving 155 participants diagnosed with schizophrenia or schizoaffective disorder. Participants were randomized to receive either ACT + CBSST (n = 75) or ACT alone (n = 80). Assessments occurred at baseline, 9 months (n = 100), and 18 months (n = 67) to capture real-time reports of "productive" and "non-productive" activities. The primary outcome was productive activity. Secondary outcomes included non-productive activity, the productive/non-productive activity ratio, anhedonia, and defeatist beliefs. Linear mixed models were used to test for differential changes over time between groups.

Study results: Although the groups differed at baseline, the ACT + CBSST group showed significantly greater improvements over time relative to the ACT group in productive activities, the productive/non-productive activity ratio, and in reductions in anhedonia and defeatist beliefs. However, between-group differences at follow-up were not statistically significant.

Conclusions: Adding CBSST to ACT may yield greater improvements in daily-life functioning than ACT alone. While these results support the potential added value of integrating CBSST into routine care, further research is needed to confirm its superiority. Together with the companion report from this study, these findings suggest that EMA may offer a sensitive approach for detecting changes in real-world functioning in clinical trials.Trial Registration: ClinicalTrials.gov (NCT02254733; https://clinicaltrials.gov/).

Background and hypothesis: Review studies find negative beliefs account for a small amount of the variance in negative symptoms and functioning. Recovery-Oriented Cognitive Therapy (CT-R) theory postulates positive beliefs as an additional causal factor.

Study design: Two convenience datasets-including indices of beliefs, negative symptoms, positive symptoms, and community functioning-were utilized: a test-retest database (Study 1 and Study 2, n = 285); the CT-R condition of an RCT (Study 3, n = 31).

Study results: Study 1 finds that positive and negative beliefs are independent and not highly correlated with each other at baseline (r = -0.4); an exploratory factor analysis also suggests this 2 factor solution. Study 2 finds significant prediction of positive beliefs at baseline with negative symptoms (β = -0.21; P = .001), and community functioning (β = 0.29; P = .002) 6 months later. Study 3 finds a significant correlation between increase in positive belief endorsement and improvement in community functioning in the CT-R condition across 24-months (r = 0.39, P < .05). The correlation between positive belief endorsement and negative symptom improvement was not statistically significant but showed a medium effect size (r = -0.26; P > .05). Change in positive beliefs were not significantly associated with positive symptom improvement. Negative beliefs were not significantly associated with change in any of the RCT outcomes.

Conclusions: The hypothesis that positive beliefs are related in the predicted direction to negative symptoms and functioning is supported, adding to an emerging literature. We point out the treatment implications of this result, utilizing CT-R theory, and discuss future research directions.

Background and hypothesis: This study aims to develop a placebo response and dropout rate model for acute-phase schizophrenia medication trials and assess factors affecting this response to inform future trial design.

Study design: We conducted a literature update using a comprehensive meta-analysis of schizophrenia medication trials, focusing on oral placebo-controlled studies. We modeled the placebo response on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions-Severity of Illness (CGI-S) scale over time and analyzed dropout rates. Influential factors were explored using covariate models and subgroup analyses.

Study results: Aggregate-level data from 48 publications were analyzed. The placebo response reached a plateau at different weeks for PANSS and CGI-S scale scores. The lower the baseline of PANSS total score, older age, heavier body weight, a higher proportion of male or Black patients, smaller sample sizes, single-country trials, older studies, and the use of the Last Observation Carried Forward imputation were associated with a lower placebo response. Maximum response of PANSS Total score and gender significantly influenced dropout rates.

Conclusions: We present a model predicting placebo response in schizophrenia trials, offering insights into the impact of various trial characteristics, aiding in the design and interpretation of future clinical studies.

Background: A recent theme in the development of psychological interventions for hearing voices (auditory verbal hallucinations) has been the emergence of a group of overlapping approaches increasingly referred to as relational therapies: Relating Therapy (RT), Talking with Voices (TwV), and AVATAR Therapy (AT).

Study design: Collaborative discussion among a group of researchers involved in developing these interventions combined with a systematic literature search were used to review this new genre, aiming to develop an agreed operationalisation; and identify common and distinctive aspects; potential mechanisms; and collective research directions.

Study results: Relational therapies for voices can be operationalised as those that "consider patterns of interaction, and/or the relational dynamics between hearer and voice, as targets for therapeutic change, and use an experiential process of dialogue with identities associated with voices as a primary therapeutic method." Key differences involve the type of experiential hearer-voice dialogue used (ie, role-play chair work, direct dialogue with voices, and recreations of voice hearing using a computerised avatar), plus varying emphasis on models of interpersonal relating, broader relationships, and meaning encapsulated within voice-hearing experiences. AT has been found efficacious in several randomised controlled trials, with RT supported by evidence from two trials, and a multicentre trial for TwV underway. Mechanism domains include hearer-voice relating; habituation; threat and safety appraisals; and reformulation and integration of experiences.

Conclusions: Common features and mechanisms can be identified across the relational therapies. Key future directions include considering what works for whom; how therapy influences voice phenomenology; the role of relational models; and implementation.

Background and hypothesis: A large body of literature suggests that neurocognitive processes underlying the sense of agency are disrupted in schizophrenia. We here tested the sense of agency in schizophrenia patients, by controlling for the potential confounding effect of temporal perception biases, antipsychotics, attentional-executive functioning, and illness duration. We also analyze the role of symptoms such as delusions, hallucinations, and passivity experiences.

Study design: We capitalized on the intentional binding phenomenon, an implicit measure of the sense of agency. 30 schizophrenia patients and 30 healthy controls completed 2 tasks. Experimental task participants pressed a switch to turn a light bulb on (active condition) or let their finger be moved by an automated switch (passive condition). They then judged the interval between the action (active or passive) and the lighting of the bulb. Control task participants estimated the time interval between two light flashes presented in sequence. All participants underwent a comprehensive neuropsychological assessment, while schizophrenia patients were also evaluated for positive, negative symptoms, and passivity symptoms.

Study results: Control participants showed the expected intentional binding effect, particularly at shorter action-outcome delays. In contrast, the effect was absent in schizophrenia patients. The alteration was significantly moderated by temporal perception biases, hallucinations, and delusions.

Conclusions: The study provides the first evidence in favor of the relationship between agency disturbances, symptomatology, and temporal perception biases in schizophrenia while excluding putative confounding factors like neuroleptics. Results are discussed in the light of a recent predictive coding model of the sense of agency.

High variety in treatment responses is expectable in heterogenous patient groups, such as in individuals with psychosis receiving cognitive behavioral therapy (CBTp). However, knowledge about the diverse trajectories to improvement is limited. This study therefore aimed to detect subgroups of individuals with psychosis with different patterns of change and to identify the covariates associated with these different trajectories. We analyzed data from a sample of individuals with a psychotic disorder (N = 108) who had received CBTp in two German outpatient clinics. Session-by-session measures included general psychopathology to assess symptomatic response and a short version of a patient-reported outcome measure of psychological recovery assessing coping with distressing symptoms, emotions and situations. Growth mixture models were used to identify subgroups of individuals that differed in their trajectories of treatment responses within the first 25 sessions of treatment. For general psychopathology, three distinct trajectories (Symptomatic Response, 50.6%; Symptomatic Non-response, 39.6%; Symptomatic Rebound, 9.9%) and for psychological recovery, two distinct trajectories (Recovery Response, 67.6%; Recovery Non-response, 32.4%) were identified. Post hoc analyses revealed that 90% of those with a symptomatic response also belonged to the recovery response trajectory group. Higher psychotic symptom scores, lower functioning and longer duration of disorder were associated with the symptomatic rebound trajectory. The results underline the encouraging potential of identifying response patterns. The knowledge gained by this type of research can provide a basis for empirically-derived decision rules for clinicians working with this heterogeneous patient group.

Background and hypothesis: Eosinophilia has not been highlighted in clozapine-induced adverse inflammatory events, as it is often asymptomatic and self-limiting, while drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome occurs rarely. This study aimed to reveal the temporal relationships between eosinophilia and other inflammatory events during clozapine initiation.

Study design: The temporal relationships between eosinophilia and other inflammatory events were evaluated among 241 patients with schizophrenia treated with clozapine for the first time at 7 hospitals. Risk factors for eosinophilia were investigated among preceding inflammatory events and other clinical characteristics. Furthermore, patients with eosinophilia were stratified by the severity of adverse inflammatory events and their clinical characteristics were compared.

Study results: Of the 54 patients who experienced inflammatory adverse events, 27 (50%) developed eosinophilia. In all but 1 patient, clinical symptoms of inflammatory adverse events preceded eosinophilia. In contrast, of the 187 patients without inflammatory events, 21 (11%) developed eosinophilia. Multivariate analysis revealed that more severe preceding inflammatory adverse events were associated with a greater risk of eosinophilia. The median time to the first detection of eosinophilia and peak eosinophil count occurred significantly earlier in patients with severe adverse events than in asymptomatic patients.

Conclusions: In most cases, eosinophilia developed after the onset of inflammatory symptoms. Preceding inflammation was associated with the development of clozapine-induced eosinophilia. Eosinophilia may not be suitable as an early detection marker of severe inflammatory adverse effects. These findings enhanced our understanding of the involvement of eosinophilia in clozapine-induced inflammatory events.

Background and hypothesis: Abnormalities in the retina are observed in psychotic disorders, especially in schizophrenia.

Study design: Using spectral-domain optical coherence tomography, we investigated structural retinal changes in relatively metabolic risk-free youth with clinical high-risk (CHR, n = 34) and first-episode psychosis (FEP, n = 30) compared with healthy controls (HCs, n = 28).

Study results: Total retinal macular thickness/volume of the right eye increased in FEP (effect sizes, Cohen's d = 0.69/0.66) and CHR (d = 0.67/0.76) compared with HCs. Total retinal thickness/volume was not significantly different between FEP and CHR. Macular retinal nerve fiber layer (RNFL) thickness/volume of the left eye decreased in FEP compared with HCs (d = -0.75/-0.66). Peripapillary RNFL thickness was not different between groups. The ganglion cell (GCL), inner plexiform (IPL), and inner nuclear (INL) layers thicknesses/volumes of both eyes increased in FEP compared with HCs (d = 0.70-1.03). GCL volumes of both eyes, IPL thickness/volume of the left eye, and INL thickness/volume of both eyes increased in CHR compared with HCs (d = 0.64-1.01). In the macula, while central sector thickness/volume decreased (d = -0.62 to -0.72), superior outer (peri-foveal) sector thickness/volume of both eyes increased (d = 0.81 to 0.86) in FEP compared with HCs.

Conclusions: The current findings suggest that distinct regions and layers of the retina may be differentially impacted during the emergence and early phase of psychosis. Consequently, oculomics could play significant roles, not only as a diagnostic tool but also as a mirror reflecting neurobiological changes at axonal and cellular levels.