Schizophrenia bulletin open最新文献

Background: This post hoc analysis examined the efficacy of aripiprazole lauroxil (AL) by baseline severity of illness in the double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness study (NCT03345979) in patients with schizophrenia treated with AL every 2 months.

Study methods: Adults with acute schizophrenia were randomized to AL 1064 mg every 2 months or active control (paliperidone palmitate [PP] 156 mg monthly). Based on Clinical Global Impression-Severity scores, baseline severity of illness was categorized as moderate, marked, or severe. Changes from baseline in Positive and Negative Syndrome Scale (PANSS) Total score were assessed at week 25, along with PANSS items related to hostility/excitement. Numbers of patients with activation adverse events (AEs; anxiety, agitation, and insomnia) were also evaluated.

Study results: Of 99 patients assigned to AL, 31 (31%) were moderately ill at baseline, 54 (55%) were markedly ill, and 14 (14%) were severely ill. With AL treatment, mean ± SE changes from baseline in PANSS Total score at week 25 were -21.1 ± 2.5 (moderately ill; baseline, 87.1), -24.1 ± 1.8 (markedly ill; baseline, 95.3), and -25.6 ± 6.4 (severely ill, baseline, 106.1). Improvements from baseline in PANSS scores related to hostility/excitement items were comparable among severity subgroups. No clear pattern of occurrence of the AEs anxiety, agitation, and insomnia was observed across baseline severity groups.

Conclusions: In this post hoc analysis, safety related to activation and efficacy with AL treatment were comparable across baseline severity-of-illness subgroups of patients with schizophrenia.

Background: Heterogeneity in schizophrenia spectrum disorders is a major challenge to implementing personalized medicine and uncovering etiological pathways. Recent work identified subtypes of schizophrenia that exhibit unique patterns of clinical symptoms and features using a common clinical scale. The current study sought to: (1) replicate prior identification of subtypes using the Positive and Negative Syndrome Scale (PANSS) in a new cohort of people with schizophrenia; (2) further characterize differences between subtypes in symptoms, affect, cognition, functioning, and personality; and (3) determine if brain structure abnormalities vary across subtypes.

Study design: Phenotypic data were obtained on 356 individuals with schizophrenia spectrum disorders. Structural brain magnetic resonance imaging data were acquired on a subset of 203 individuals with schizophrenia and 186 healthy people. A 2-step cluster analysis of PANSS data was used to identify subtypes of schizophrenia. Subtypes were compared on characteristics and brain volume.

Study results: Clustering revealed 3 clusters aligning with previous subtypes: distress, negative, and low symptom. The distress subtype demonstrated higher levels of negative emotions, neuroticism, and schizotypal personality traits. The negative subtype exhibited more severe cognitive impairment, higher levels of disorganized and anhedonia symptoms, and worse functioning. Abnormalities in cortical volumes followed a gradient, the negative subtype demonstrated the largest number of cortical regions with smaller volume relative to healthy people, followed by the distress subtype, then the low symptom subtype. In contrast, smaller subcortical volumes were consistent across subtypes.

Conclusions: Our findings support the presence of subtypes of schizophrenia spectrum disorders that differ in affect, cognition, functioning, personality, and brain structure.

Background and hypothesis: Theoretical models and empirical evidence suggest that paranoid thoughts stem from a heightened sense of vulnerability, including the perception of the world as dangerous, and fears of rejection and social evaluation. However, the factors contributing to this sense of vulnerability and the complex interplay between these elements remain underexplored.

Study design: A total of 175 individuals recruited from a nonclinical community sample, including 103 participants with low levels of paranoid thoughts (LP) and 72 with high levels (HP), took part in a 7-day ESM study assessing momentary levels of paranoia, social functioning, social rejection, negative affect, body image, and misophonia symptoms. Temporal, contemporaneous, and between-subject network models were estimated for the total sample and its subgroups separately.

Study results: The temporal network identified paranoid thoughts as a predictor of negative affect, feelings of rejection, and negative body image, while in turn being predicted by feelings of rejection and reduced social safety. A bidirectional relationship between paranoia and social rejection emerged. These findings were supported by contemporaneous and between-subject networks, which showed that paranoid thoughts co-occurred with and were, on average, linked to feelings of rejection, negative affect, and reduced social safety.

Conclusions: These findings suggest that social rejection plays a central role in paranoia. While group differences in network structure were modest, the HP group exhibited more numerous and stronger connections between variables, suggesting that paranoia may develop through the gradual reinforcement of connections between symptoms rather than structural shifts, highlighting the importance of early intervention.

Background: Psychosis may be conceptualized as a spectrum disorder, with psychotic experiences (PEs), fleeting, subtle symptoms not warranting clinical presentation-at its mildest end. The thalamus, particularly its pulvinar region, is implicated in coordinating cortical synchrony and attention, and may contribute to psychosis. Reduced pulvinar volumes have been observed in severe psychosis and in individuals lower on the spectrum. This study examines thalamic nuclei changes in young adolescents with PEs.

Methods: A community-based sample of 95 adolescents aged 11-13 years (53 with PEs, 42 healthy controls) underwent magnetic resonance imaging (MRI), with thalamic nuclei volumes calculated using Freesurfer. Magnetic resonance imaging (MRI) was repeated at 2- and 5-year follow-up. Analyses of covariance and linear mixed-effects (LME) models assessed group-wise differences at each timepoint (TP) and longitudinally. Individual nuclei were recombined into anatomical composites (eg, pulvinar, ventral) for targeted analysis.

Results: Compared with controls, adolescents with PEs had significantly smaller left pulvinar composite volumes at TP2 (P = .01) and TP3 (P = .019). Linear mixed-effects revealed a significant longitudinal reduction in left pulvinar volume (P = .008, false discovery rate [FDR]-corrected) and a significant increase in left ventral volumes (P = .013, FDR-corrected).

Conclusions: Thalamic changes linked to higher-risk psychotic states appear detectable in nonclinical adolescents with subthreshold PEs. This divergence from normative developmental trajectories may indicate early alterations in neural circuits governing attention, cortical synchrony, and dopaminergic function. Identifying such early deviations could refine our understanding of psychosis vulnerability. Replication in larger, more diverse cohorts is warranted to confirm these preliminary findings and assess their predictive value.

Background and hypothesis: The overarching objective when studying schizophrenia is the development of generalizable knowledge that improves patient health and/or increases our comprehension of their illness. To fully achieve this objective, investigations need to reflect the full range of individual variation found within this heterogeneous population. But individuals committed to state psychiatric institutions have been routinely excluded from research because of concerns that they may not be able to understand or provide adequately informed consent. While reasonable, we believe this approach has enabled policies that support implicit bias, contribute to health care disparities, and limit our knowledge of disease mechanisms and treatment.

Study design: This article provides brief reviews of (1) ethical considerations when recruiting individuals with severely treatment-resistant psychotic symptoms for research, (2) the impact their condition has on decision-making capacity, and finally (3) we provide a first-hand narrative of our experience conducting a genomic study of involuntarily hospitalized individuals and the opportunities/obstacles we encountered.

Study results: Evidence from published literature shows that cognitive impairment, rather than severity of psychopathology, is the greatest threat to decisional capacity. Ethical safeguards and practical considerations have been developed, including (1) institutional/local research committee review and approval, (2) confidentiality, (3) informed consent, (4) assessment of capacity, and (5) community engagement. Our experience demonstrates that carefully selected involuntarily committed individuals can be included in research.

Conclusions: With ethical safeguards, these individuals deserve the opportunity to volunteer for research regarding the mental illness that has profoundly shaped their lives-to do otherwise is discriminatory.

Background and hypothesis: The Early Psychosis Intervention-Spreading Evidence-Based Treatment (EPI-SET) is a study evaluating the implementation and impact of NAVIGATE, a manualized model of care for first episode psychosis in geographically diverse EPI programs in Ontario. Project Extension for Community Health Outcomes (ECHO), a virtual training and capacity-building model, was used to support the NAVIGATE implementation for participating programs. We evaluated ECHO EPI-SET in supporting this implementation.

Methods: Using Moore's Evaluation Framework for Continuing Education, attendance and biweekly surveys were used to evaluate clinician engagement and satisfaction with ECHO. A self-reported survey was used to assess self-efficacy across core competencies, determine whether ECHO changed their practice, and describe the nature of any changes. Semi-structured interviews focusing on participants' experience with ECHO EPI-SET were analyzed using thematic analysis.

Results: A total of 92 participants from 6 EPI sites participated across 3 cycles of ECHO EPI-SET. Mean satisfaction ratings were high (>4/5 on a Likert scale). Participants who worked longer at their sites reported higher rates of self-efficacy. The interviews identified 5 major themes: creating a community of practice; supporting NAVIGATE; change in practice/application; implementation support; and strengths and areas for improvement.

Conclusions: This is the first published evaluation of using ECHO in supporting the implementation of a model of EPI care. Participation in ECHO was associated with high levels of clinician satisfaction, engagement, and self-efficacy. Qualitative data suggest that ECHO supported the development of a community of practice, learning, and practice change and may be a helpful tool to support future implementations of NAVIGATE.

Background: This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants.

Methods: The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs. Key measures include the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the Structured Interview for Psychosis-Risk Syndromes, which determined CHR criteria and the severity of attenuated psychotic symptoms (APS). Other measures included the Structured Clinical Interview for DSM-5, scales to assess negative symptoms, depression, suicidal ideation, substance use, social and role functioning, and a selection of patient-reported outcomes.

Results: CHR participants presented with more severe ratings on all clinical measures and poorer functioning relative to the CC. There were a few significant small associations between measures of APS and other clinical measures.

Conclusion: The results from this study support previous research indicating that CHR individuals face serious clinical challenges beyond the risk of developing psychosis. Findings indicate significant associations among various clinical measures, underscoring the complex nature of the CHR population. Limitations are acknowledged, including the preliminary nature of the data and the need for more in-depth analyses from AMP SCZ papers already in progress. Future work will focus on longitudinal data and further exploration of clinical variables and their relationship with biomarkers.

Background: This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants.

Methods: A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various methods, including referrals from healthcare providers, schools, and community agencies, and self-referrals via outreach efforts and advertising.

Results: Participants were recruited from 13 different sources, with self-referral being the most common for both CHR and CC. Other notable sources included child and youth services and psychiatric hospitals and departments. Regional differences in recruitment patterns were observed across continents. Differences in age, APS, and social functioning for CHR participants were examined in the top 5 recruitment sources. Overall, self-referred individuals were typically older, with less severe APS and higher levels of functioning, whereas those from adult community mental health services had poorer functioning and more severe APS. The remaining recruitment groups fell between these 2 extremes.

Conclusion: This paper highlights the diverse recruitment sources for the AMP SCZ program. Self-referral was a significant source, particularly in North America, reflecting changing help-seeking behaviors influenced by the internet and social media. The findings underscore the importance of understanding recruitment sources to optimize future CHR research.