Schizophrenia Bulletin最新文献

Background and hypothesis: Persistent distressing psychotic-like experiences (PLE) are associated with impaired functioning and future psychopathology. Prior research suggests that physical activities may be protective against psychopathology. However, it is unclear whether physical activities may interact with genetics in the development of psychosis.

Study design: This study included 4679 participants of European ancestry from the Adolescent Brain Cognitive Development Study. Persistent distressing PLE was derived from the Prodromal-Questionnaire-Brief Child Version using four years of data. Generalized linear mixed models tested the association between polygenic risk score for schizophrenia (PRS-SCZ), physical activities, and PLE. The models adjusted for age, sex, parental education, income-to-needs ratio, family history of psychosis, body mass index, puberty status, principal components for PRS-SCZ, study site, and family.

Study results: PRS-SCZ was associated with a greater risk for persistent distressing PLE (adjusted relative risk ratio (RRR) = 1.14, 95% CI [1.04, 1.24], P = .003). Physical activity was associated with less risk for persistent distressing PLE (adjusted RRR = 0.87, 95% CI [0.79, 0.96], P = .008). Moreover, physical activities moderated the association between PRS-SCZ and persistent distressing PLE (adjusted RRR = 0.89, 95% CI [0.81, 0.98], P = .015), such that the association was weaker as participants had greater participation in physical activities.

Conclusions: These findings demonstrate that the interaction between genetic liability and physical activities is associated with trajectories of distressing PLE. Further research is needed to understand the mechanisms of physical activities and genetic liability for schizophrenia in the development of psychosis.

Background: There is little head-to-head data comparing cognitive behavior therapy for psychosis (CBTp) and antipsychotic medication (APs). However, several recent trials have been conducted in first episode psychosis. We report a pre-specified individual participant data (IPD) pooled analysis utilizing data from two randomized controlled trials (RCTs) with similar designs to examine relative effectiveness.

Study design: The outcomes were psychiatric symptoms (Positive and Negative Syndrome Scale: PANSS) and recovery (Questionnaire about the Process of Recovery: QPR) at 6 months. One-stage and two-stage IPD meta-analyses were performed based on the intention-to-treat principle. Serious adverse events are also summarized.

Study results: Two RCTs were included in the pooled IPD analysis which provided 136 participants. For PANSS total at 6 months, the one-stage meta-analysis found no evidence of a difference between CBTp alone and APs alone (mean difference 2.58, 95% CI, -2.83 to 7.98; P-value 0.35) and CBTp alone compared with APs plus CBTp (MD -5.91; 95% CI, -12.14 to 0.31; P-value 0.063). For APs alone compared to CBTp plus APs there was evidence of a difference (MD -8.49; 95% CI, -14.65 to -2.33; P-value 0.007) favoring the combined treatment. For user-defined recovery (QPR), there was a difference favoring CBTp plus APs in comparison to both CBTp alone (P-value 0.029) and APs alone (P-value 0.026), but no difference between the monotherapies (P-value 0.91). The most common serious adverse events were psychiatric hospital admissions.

Conclusions: Cognitive behavior therapy for psychosis and APs did not differ in their effects on symptoms or recovery, but there were suggestions that the combined treatment may be superior. A definitive RCT is warranted.

Background and hypotheses: Sexual minority populations have a higher prevalence of psychotic experiences (PE), possibly due to differential experiences within the social envirome in its positive (eg, social support, parenting) and negative aspects (eg, adverse life events, bullying). This study hypothesized that (1) sexual minority adolescents experience more PE, (2) are more exposed to harmful aspects of the social envirome, and (3) may display differential sensitivity to certain aspects of the social envirome.

Study design: Data from 678 adolescents (mean age 15.6 years) were analyzed. Psychotic experiences were assessed using the Prodromal Questionnaire 16 (PQ-16). Aspects of the social envirome (childhood adversity, bullying, parenting style, and social support) were evaluated using different questionnaires.

Study results: The odds ratio of having sexual minority status (SMS) was 1.98 (95 CI%, 1.02-3.84) for participants with PE (PQ-16 ≥ 6) compared to participants without. Significant associations were found between SMS and more adverse childhood experiences (95% CI, 0.11-3.51) and parenting psychological control (95% CI, 0.11-0.53), and less parenting autonomy support (95% CI, -0.37 to -0.01). There were also significant differential effects: adverse childhood experiences were associated with PE in heterosexuals but not in sexual minorities (95% CI, -0.34 to -0.03), while less social support was associated with more PE in heterosexuals but less PE in sexual minorities (95% CI, 0.06-0.39).

Conclusions: Sexual minority status is associated with a higher prevalence of PE, greater exposure to harmful factors within the social envirome, and differential effects on sexual minority and heterosexual individuals. These results emphasize the need for a fine-grained analysis of the envirome to understand the increased risk for PE in sexual minorities.

Background and hypotheses: Negative symptoms of schizophrenia (NSS) carry a substantial burden, and there are no treatments currently approved for NSS. The efficacy of pimavanserin, a selective 5-HT2A inverse agonist and antagonist, in treating NSS was assessed.

Study design: ADVANCE-2 was a phase 3, randomized, double-blind, placebo-controlled study of pimavanserin in patients with schizophrenia and predominantly negative symptoms. Patients were randomized (1:1) to receive pimavanserin (34 mg/day) or placebo alongside ongoing background antipsychotic medication. Eligible adults were aged 18-55 years and had access to a caregiver. The primary and key secondary endpoints were the change from baseline to week 26 in the Negative Symptom Assessment-16 (NSA-16) total score and Clinical Global Impression-Schizophrenia Scale-Severity (CGI-SCH-S) negative symptom score, respectively.

Study results: Of the 454 randomized patients, 71 (39 placebo; 32 pimavanserin) discontinued and 383 (188 placebo; 195 pimavanserin) completed the study. The safety and full analysis sets comprised 453 and 446 patients, respectively. The NSA-16 change from baseline to week 26 was not significantly different between groups (least squares mean difference: -0.67; SE, 0.95; [95% CI: -2.54, 1.20]; P = .48; Cohen's d effect size: 0.07). Treatment-emergent adverse events occurred in 30.4% with pimavanserin and 40.3% with placebo.

Conclusions: In this study, pimavanserin was well tolerated, and although it demonstrated a similar treatment effect as in the prior phase 2 study favoring pimavanserin, treatment with pimavanserin vs placebo did not result in significant differences for primary or other endpoints.

Background and hypothesis: People with serious mental illness (SMI) have an increased risk of suicide ideation (SI) and suicide behavior (SB). Longitudinal studies on factors contributing to SI/SB in SMI are lacking. Interpersonal biases (ie, perceived burdensomeness and thwarted belongingness) are cross-sectionally related to SI/SB, but do they relate to longitudinal suicide risk or other illness factors? Ecological momentary assessment (EMA) offers a powerful approach to a deeper understanding of these complex relationships.

Study design: Participants with SMI (N = 180) completed 3 in-lab visits (baseline, 6-month, and 12-month) and 10 days of EMA (3×/day) following the baseline visit. At all timepoints, participants were assessed for SI/SB and were classified as persistent, intermittent, or no SI or any reports of SB over the 12-month follow-up. Multinomial logistic regression models examined whether EMA burdensomeness, belongingness, social motivations, and psychotic symptoms predicted SI persistence or SB over 12 months. Time-series network analysis compared participants' EMA data by baseline SI.

Study results: Burdensomeness and belongingness related to persistent SI 12 months, as did voices, suspiciousness, and social motivations. Only burdensomeness and belongingness related to increased risk of SB over 12 months. Network analyses revealed unique lagged relationships in the baseline SI group: of suspiciousness to belongingness and social avoidance motivation to burdensomeness when compared to the baseline group without SI.

Conclusions: These findings indicate the importance of interpersonal risk factors and suspiciousness to trajectories of SI and SB over 12 months in SMI. Pending replication, these constructs may be potential suicide prevention treatment targets in SMI.

Background: The reduced interest in, pleasure from, and motivation for social connection (clinically referred to as social anhedonia) significantly contributes to social dysfunction in schizophrenia. However, social anhedonia in schizophrenia has been challenging to treat. A new wave of psychosocial interventions for anhedonia, referred to as "positive affect interventions", have been validated in depression, but have not been widely applied in schizophrenia.

Study design: The goal of this narrative review article is to introduce positive affect interventions as a novel approach to treat social anhedonia in schizophrenia. We provide a narrative review of (1) the current psychosocial interventions for motivational deficits in schizophrenia; (2) the current positive affect intervention strategies for motivational deficits in depression; (3) the reward mechanisms (responsivity, learning, and valuation) that may differentially impact treatment response in schizophrenia vs depression; and (4) adaptations that might be needed to implement positive affect interventions in schizophrenia.

Study results: Compared with current psychosocial interventions for motivational deficits in schizophrenia, positive affect interventions have a greater emphasis on increasing positive affect (via reward mechanisms) to increase motivated social behavior. Adaptations of positive affect interventions to treat social anhedonia in schizophrenia might consider challenges with social goal-setting, negative social interactions, and social avoidance.

Conclusions: Psychosocial interventions that target positive affect could ultimately lead to greater improvements in social connection in schizophrenia. Recommendations for next steps to validate positive affect interventions to treat social anhedonia in schizophrenia are discussed.

AVATAR therapy involves facilitated dialogs between a voice hearer and a digital embodiment of their distressing voice ("the avatar"). We conducted a multi-site single-blind randomized controlled trial to evaluate the efficacy of brief (AV-BRF) and extended (AV-EXT) forms of AVATAR therapy, compared with treatment as usual (TAU) alone (AVATAR2). This study reports the data from experience sampling method (ESM) assessments conducted at baseline, end of therapy (16 weeks), and follow-up (28 weeks). The research questions focused on whether those in the AV-BRF or AV-EXT arms experienced less voice-related distress, anxiety, and beliefs as measured by ESM, compared to TAU. Separate mixed-effects models were fitted for each research question. The final sample (n = 200) completed approximately 40% of questionnaires across all timepoints. Participants who received AV-EXT therapy, but not AV-BRF, reported reduced momentary voice-related distress at 16 (P = .022) and 28 weeks (p = .029). Appraisals of voice control were also reduced in the AV-EXT arm at 16 weeks when the voice was present (P = .002) or not (P = .008). Voice power appraisals were reduced (P < .035) in both arms when the voice was "not present but on my mind" at all timepoints. There were no changes in the frequency of voice hearing, appraisals of voice intent, or assertive responding. These findings from everyday life, reported for the first time, provide evidence of the impact on the primary AVATAR therapy treatment targets, including appraisals of voice power and control. The weight of evidence favors the AV-EXT protocol in the further development and implementation of AVATAR therapy.

Background and hypothesis: Psychotic and traumatic-stress symptoms commonly co-occur. Psychological interventions have increasingly targeted these co-occurring symptoms. However, information on their efficacy, tolerability, and acceptability is limited in this evolving field.

Study design: After preregistration at PROSPERO (CRD42024553934), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of psychological interventions with persons aged 16+ reporting both psychotic and traumatic-stress symptoms. PubMed, CINAHL, Embase, PsycINFO, Clinicaltrials.gov, and Web of Science were searched in July 2024. We used the Revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB-2) for bias assessment. Random-effects models were used to synthesize clinical outcomes, while meta-regression was applied when 10 effect sizes were reported per outcome.

Study results: We included 10 RCTs with 559 participants. Interventions primarily targeted trauma-related symptoms and were seemingly tolerable and acceptable, with low adverse event profiles and a dropout rate of 14%. In comparison to usual treatments and active control treatments, interventions significantly decreased traumatic-stress symptoms at post-treatment (g = 0.33, 95% CI [0.08, 0.57]), with meta-regression favoring interventions primarily employing exposure (gdiff = 0.59, [0.22, 0.97]). Interventions significantly decreased traumatic-stress symptoms at follow-up (g = 0.34, [0.12, 0.56]), but not total psychotic, positive, or negative symptoms at either timeframe.

Conclusions: Findings suggest that psychological interventions for co-occurring psychotic and traumatic-stress symptoms are safe, tolerable, and may reduce traumatic-stress symptoms when employing exposure. Considering the substantial risk of bias, the small number of trials, non-significant results for other clinical and functional outcomes, and unexplained heterogeneity, further research is needed.

Background and hypothesis: The efficacy of yoga as an adjunctive treatment for schizophrenia spectrum disorders (SSD) has garnered interest. While yoga may positively influence various symptom domains, further investigation is needed due to the limited number, quality, and generalizability of studies. This study assessed the feasibility and acceptability (primary outcome) of a yoga-based group intervention (YoGI) developed in a participatory approach and explored its preliminary effectiveness.

Study design: In addition to the primary outcomes, this preregistered randomized controlled trial examined rater-blinded general psychopathology, positive- and negative symptoms, and self-rated depression, anxiety, stress, body mindfulness, mindfulness, psychological flexibility, cognition, social functioning, quality of life, and medication regime at baseline and postintervention as secondary outcomes.

Study results: Fifty inpatients with SSD received either TAU (n = 25) or YoGI + TAU (n = 25) for four weeks. Outcomes showed 95% protocol adherence of YoGI, feasibility, and retention rates of 91% and 94%, respectively, and a dropout rate of 6%. ANCOVA revealed significant between-group postintervention improvements for YoGI + TAU in positive symptoms, depression, cognitive fusion, and a mindfulness subscale. Medium-to-large pre- to postintervention effects were found for body mindfulness, positive, negative, and general psychopathology, cognitive fusion, depression, anxiety, stress, quality of life, and attention in YoGI + TAU, while within-group changes were consistently smaller in TAU. No severe adverse events were reported.

Conclusions: This trial supports the feasibility and acceptability of YoGI for inpatients with SSD and provides preliminary evidence of YoGI's benefits beyond TAU. Further robust, multicentric RCTs are warranted to deepen our understanding of YoGI's therapeutic potential and inform clinical interventions for SSD.

Background: A theory-driven cognitive therapy (Feeling Safe) has produced much better outcomes for patients with persecutory delusions. There are four distinct response classes: very high delusion conviction with large improvement, very high delusion conviction with no response, high delusion conviction with large improvement, and high delusion conviction with modest improvement. Our objective was to apply principal trajectories analysis, a novel statistical method, to original trial data to estimate whether these groups may have responded differently to a different intervention: befriending.

Design: One hundred and thirty patients with persistent persecutory delusions were randomised to six months of Feeling Safe or befriending. Baseline assessments were used to assign patients allocated to befriending (who did not receive Feeling Safe) into the four Feeling Safe response classes. The treatment effect, including on potential mediators, was then estimated for these classes.

Results: Patients in two treatment response classes (Very high conviction/large improvement, High conviction/large improvement) benefited more from Feeling Safe, patients in one group (Very high conviction/no improvement) benefited more from befriending, and patients in the remaining group (High conviction/moderate improvement) benefited equally from the interventions. Mechanism differences were detected when Feeling Safe was superior to befriending, but not when befriending was superior.

Conclusions: There may be patients with psychosis who benefit more from one type of therapy than another, likely due to different change mechanisms. The application of principal trajectories has generated testable hypotheses and a potential step toward personalised treatment. We recommend an investigation of whether sequential provision of the treatment types could enhance patient outcomes. Keywords: persecutory, delusions, outcome trajectories, psychosis, cognitive therapy.