Schizophrenia Bulletin最新文献

Background: Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear.

Design: We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA.

Results: We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights.

Conclusions: Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.

Background and hypothesis: Pregnant women with persistent schizophrenia and related disorders may require ongoing antipsychotic treatment, including clozapine. However, the potential risks of using clozapine during pregnancy and the postnatal period remain uncertain.

Study design: We conducted a nested case-control study using the National Register of Antipsychotic Medication in Pregnancy (NRAMP) database. Our study assessed pregnancy outcomes among Australian women diagnosed with schizophrenia spectrum disorder and treated with clozapine (n = 14) during the first trimester. These women were compared to 2 subgroups: those treated with quetiapine (n = 53) and those not taking any medication (n = 24) during pregnancy.

Study results: We observed higher rates of miscarriage in the clozapine group compared to the quetiapine and drug-free groups. The clozapine group had a higher early pregnancy body mass index but lower overall pregnancy weight gain than the other groups. The prevalence of gestational diabetes was significantly higher in the clozapine group. The percentage of vaginal delivery was higher in the clozapine group than in the other 2 groups. Neonatal outcomes such as gestational age, and Apgar scores were similar across groups. The birth weight was lower in the clozapine group compared to the other 2 groups.

Conclusions: This study suggests that pregnant women taking clozapine and their babies have greater adverse outcomes compared to other groups. Clozapine appears to be associated with a greater risk of miscarriages, maternal gestational diabetes, and lower birth weight. However, the gestational age, Apgar scores, and admission to NICU/SCN were comparable between all groups.

Background and hypothesis: Prior research links a shorter paracingulate sulcus (PCS) to hallucinations in schizophrenia, but its symmetry hemispheric specificity and relevance to bipolar disorders remain unclear. We hypothesized that reduced PCS asymmetry and interhemispheric gyrification covariance in salience and auditory networks are associated with lifetime auditory hallucinations (AH) in psychotic spectrum disorders.

Study design: We compared patients with and without AH, and healthy controls, focusing on PCS asymmetry in five ordinal classes, sulcal length and depth, and interhemispheric gyrification covariance.

Study results: Among 351 patients with schizophrenia or bipolar spectrum disorders (SSD/BSD), 194 (55.3%) had AH, compared to 157 without and 278 healthy controls. We found no significant PCS class asymmetry between hemispheres (V = 6648.5, P = .097) and decreased leftward asymmetry in PCS length (F(2,621) = 3.19, P = .013) in patients with AH, compared with those without and healthy controls. Compared to patients without AH, those with AH showed increased gyrification covariance in the auditory network (F(2,625) = 42.5, P < .001). In the salience network, patients with SSD and AH had increased covariance (F(2,625) = 299, P < .001), while patients with BSD and AH displayed decreased covariance (F(2,625) = 102, P < .001).

Conclusions: This study, featuring the largest cohort to date, links the AH trait to replicable reduced leftward PCS asymmetry and altered interhemispheric covariance in psychotic spectrum disorders, supporting theories of reduced asymmetry and altered brain network coordination as part of the mechanistic pathway to psychosis.

Background and hypothesis: Autophagy, the cell's primary degradation and recycling system, is essential for neuronal homeostasis. A structured synthesis of studies directly investigating autophagy in schizophrenia (SCZ) is lacking. This scoping review aimed to map the available evidence directly assessing autophagy processes in SCZ.

Study design: We systematically searched Medline (via Ovid), Embase, and PsycINFO from inception to February 2025. Twenty-four eligible studies-encompassing clinical cohorts, postmortem brain tissue, animal and cellular SCZ-relevant models-were thematically analyzed.

Study results: Findings indicated impaired autophagy in SCZ, implicating it in 3 main processes: (1) disrupted neurodevelopment/synaptic pruning, (2) lysosomal dysfunction/proteostasis, (3) compromised mitochondrial turnover/metabolic homeostasis. Antipsychotic treatment showed variable effects, with some agents partially restoring autophagic markers, whereas others heightened dysfunction. Transcriptomic studies identified autophagy-related gene signatures with potential diagnostic relevance. Synthesizing these findings, impaired autophagy emerged as a possible mechanistic link between early neurodevelopmental vulnerability and progressive cellular stress, which may underlie disease progression in some cases.

Conclusions: Autophagy dysfunction may contribute to both early neurodevelopmental and later progressive cellular changes in SCZ. However, much of the current evidence derives from cross-sectional studies, peripheral biomarkers or animal models, with limited direct evidence from the human central nervous system. These limitations constrain causal interpretation. Even so, autophagy represents a promising therapeutic target, with potential to support early neural development and prevent progressive cellular decline. Longitudinal, multimodal studies integrating peripheral and central autophagy markers with clinical outcomes are needed to clarify autophagy's role in SCZ pathophysiology and treatment.

Background and hypothesis: Drug-induced dystonia and dyskinesia are associated with increased all-cause mortality, with limited data on cause-specific mortality. We aim to confirm mortality risk and cause-specific mortality in drug-induced acute dystonia or tardive dyskinesia.

Study design: From Taiwan's National Health Insurance Database (2015-2021), we identified adults with ≥2 psychiatrist- or neurologist-confirmed diagnoses of drug-induced acute dystonia or tardive dyskinesia, and created 1:4 age- and sex-matched population controls and an unaffected sibling cohort. Outcomes included all-cause, natural-cause, and unnatural-cause mortality expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable Cox models were adjusted for sex, age, urbanization, socioeconomic status, and comorbidities.

Study results: A total of 2862 patients and 11 448 matched controls were identified. Mean age was 64.6 years, 67.2% female, mean follow-up duration was 4.5 years. Drug-induced acute dystonia or tardive dyskinesia was associated with significant excess risk of all-cause (HR = 1.51, 95% CI 1.36-1.67), natural-cause (1.39, 1.25-1.55), and unnatural-cause (3.67, 2.42-5.54) mortality. For natural-cause mortality, mortality risk was elevated for endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; nervous, circulatory, and respiratory system diseases; but reduced for neoplasms. For unnatural-cause mortality, both accidents and suicides revealed higher mortality risks. Results were similar across age groups and ten psychiatric comorbidities. Sex subgroup analysis revealed higher suicide mortality risk in females than males.

Conclusions: Drug-induced acute dystonia and tardive dyskinesia are associated with elevated all-cause, natural-cause, unnatural-cause, and cause-specific mortalities, highlighting the need for targeted interventions to prevent these specific causes of deaths.

Background and hypothesis: Cognitive deficits are central to schizophrenia-spectrum disorders and already present in many patients at first-episode psychosis (FEP). Prior meta-analyses suggest cognitive deficits remain relatively stable, but most of them tracked patients for only a few years and rarely compared trajectories directly with matched healthy controls (HCs). We aimed to characterize cognitive trajectories over long-term follow-ups.

Study design: Following PRISMA-2020 guidelines, we searched databases for longitudinal studies of cognition in recent-onset psychosis. Forty-nine datasets (3693 FEP and 1399 HCs) were included, with follow-ups ranging from 2 to 25 years. Random-effects meta-analyses quantified within-group change (FEP and HC separately) and between-group differences (FEP-vs.-HC) across short (2-5 years), mid (5-10 years), and long-term (≥10 years) intervals. Meta-regressions examined the influence of clinical moderators.

Study results: Both FEP patients and HCs showed either stable performance or small effect-size improvements in global (FEP: d = 0.22, P < .0001) and domain-specific cognition over long-term, with no evidence of progressive deterioration. Direct comparisons revealed no FEP-vs.-HC differences in global cognitive change overall (d = 0.05, P = .568) or within any follow-up interval (short, mid, and long). Across domains, the only exception was attention, where patients improved compared to controls. Changes in positive and negative symptoms were unrelated to changes in global cognition.

Conclusions: Neuropsychological performance in FEP remains stable for at least a decade, with modest gains largely attributable to practice effects and no sign of neurodegenerative decline. These trait-like deficits appear partly independent of long-term symptom changes, and further support neurodevelopmental over neurodegenerative models of schizophrenia.

Background and hypothesis: Negative symptoms are important and common concerns in individuals at clinical high risk for psychosis (CHR-P) but are not systematically utilized to predict or improve outcomes. We explored the ability of various negative symptom models to predict the onset of psychosis while controlling for potential secondary sources of these symptoms.

Study design: A total of 581 participants from the North American Prodrome Longitudinal Study (NAPLS3) were assessed at baseline, 2-, 4-, and 6-month follow-up. This included 70 high-risk individuals who transitioned to psychosis (CHR-T) and 415 who did not transition to psychosis (CHR-NT), as well as 96 healthy controls (HCs). Attenuated positive and negative symptoms were rated on the Scale of Prodromal Symptoms. Three negative symptom models were evaluated: (1) total negative symptoms; (2) experiential and expressive negative symptoms; and (3) separate analyses for each negative symptom. Depressive symptoms were determined via the Calgary Depression Scale for Schizophrenia.

Study results: Total negative symptoms differed significantly between all 3 groups across time, such that CHR-T > CHR-NT > HC (P < .001). This pattern remained after adjusting for positive and depressive symptoms (P < .001). Baseline negative symptom severity predicted psychosis (P = .007), even with positive and depressive symptoms included in the model. Similar results were observed for experiential (P = .016) and expressive (P = .027) negative symptoms as well as social anhedonia (P = .011) and ideational richness (P = .002).

Conclusions: Our findings reinforce the importance of negative symptoms in predicting psychosis in CHR-P youth. The data support consideration of negative symptoms in predictive algorithms for enhancing early recognition and treatment strategies.

Background and hypothesis: Negative symptoms (NS) impair outcomes in schizophrenia, affecting quality of life, and resisting pharmacological treatments. Scales targeting specific NS domains-eg, anhedonia, avolition, alogia, social withdrawal, and blunted affect-allow clinicians to assess how treatments affect individual symptoms, and deepen understanding of NS pathophysiology. While observer-rated scales are most widely used, self-assessment tools can provide insight into individuals' personal experiences. Here we evaluated the psychometric properties of NS self-assessment scales, focusing on tools for specific domains, to guide tailored treatments in clinical and research settings.

Study design: We conducted a comprehensive literature review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, searching MEDLINE, and Web of Science for self-assessment scales evaluating specific NS domains. Each tool's methodological quality was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist.

Study results: We identified 15 self-assessment scales: 7 for anhedonia, 7 for avolition, 1 for social withdrawal, and none for alogia or blunted affect. The Temporal Experience of Pleasure Scale was the most valuable tool for anhedonia, with a grade B recommendation. All instruments assessing avolition were assigned a grade C recommendation, due to the limited numbers of validation studies. The University of California Los Angeles Loneliness Scale Version 3 (UCLALS-V3) was the only self-report measure targeting social withdrawal, but its emphasis on depressive symptomatology weakened its recommendation for NS assessment.

Conclusion: We identified 15 promising self-assessment scales on specific NS domains. Although they require further validation notably on their sensitivity to change, they provide detailed insights into symptomatology and facilitate precise monitoring.