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: The etiology of schizophrenia involves both biological and environmental risk factors. Studying childhood trauma in disorders along the schizophrenia spectrum, including schizotypal personality disorder (SPD), can inform early risk and protective factors for psychosis. However, no study has directly compared childhood trauma between SPD and schizophrenia.

Study design: One hundred twenty-four participants (schizophrenia/schizoaffective disorder [SZ] n = 45, SPD n = 32, and healthy controls [HCs] n = 47) matched on age and gender were assessed for different types of childhood abuse and neglect as well as clinical symptoms. Kruskal-Wallis H-tests examined group differences in childhood trauma severity and logistic regression modeled childhood trauma types that were associated with an SZ vs SPD diagnosis.

Study results: SZ and SPD had greater severity than HC on total trauma score and all types of childhood trauma assessed (all P-values < .05). SZ and SPD only differed on childhood sexual abuse, which was greater in SZ (P = .039). Childhood sexual abuse (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.02-1.27, P = .02) and emotional abuse (OR = 0.82, 95% CI = 0.71-0.95, P = .01) were independent predictors of an SZ vs SPD diagnosis. Sensitivity analysis indicated that a cutoff at mild sexual abuse was significant in predicting SZ vs SPD when compared with none/minimal sexual abuse. In SZ, greater sexual abuse was associated with positive schizotypal traits and in SPD, greater emotional abuse was associated with depressive symptoms.

Conclusions: Findings suggest that childhood sexual and emotional abuse may be important factors that influence illness trajectory across the severity of disorders on schizophrenia spectrum. These findings have implications for understanding disease mechanisms and early prevention.

Objective: This study investigated the relationships between baseline peptide antigen-related IgG levels and 8-week antipsychotic drug (APD) treatment response rates and one-year treatment outcomes, as well as the relationships between changes in peptide antigen-related IgG levels and one-year treatment outcomes, in first-episode schizophrenia (FES) patients.

Methods: Sixteen peptide antigen-related IgGs from proteins encoded by schizophrenia-related genes were selected on the basis of several selection criteria from a 2022 genome-wide association study. Novel peptide antigen-related IgG levels were measured in drug-naïve FES patients at baseline (n = 155) and in plasma samples from 60 healthy controls (HCs). At the one-year follow-up, 57 patients completed both symptom and autoantibody assessments. Statistical analyses included t tests, Pearson correlation analysis, linear regression analysis, linear mixed-effects models, and simple slope analysis.

Results: Anti-MOB4 IgG and anti-PDIA3 IgG levels were significantly lower in drug-naïve FES patients compared to HCs and showed a negative correlation with baseline excitement factor scores. Baseline anti-EMB IgG levels were associated with the 8-week treatment response, whereas anti-MAD1L1 IgG levels were correlated with one-year outcomes in drug-naïve FES patients. The one-year trajectory of changes in anti-FURIN IgG, anti-MAPK3 IgG, and anti-ACTR1B IgG levels was related to remission.

Conclusion: This study revealed that patients with schizophrenia had autoimmune abnormalities, with different peptide antigen-related IgG being associated with short-term or long-term treatment efficacy, and that these antibody levels were regulated by APDs.