Schizophrenia Bulletin最新文献

Background and hypotheses: The causes of schizophrenia remain unclear, and research has been hindered by the lack of quantifiable standards. However, magnetic resonance imaging (MRI) is addressing these challenges, revealing critical neurobiological details and emphasizing its importance in both evaluation and treatment.

Study design: First, we reviewed the progress of research on structural MRI (sMRI), functional MRI (fMRI), multimodal/multiomics analysis, artificial intelligence, and neuromodulation in first-episode schizophrenia (FES) over the past 5 years. Second, we summarize the current state of schizophrenia research funded by the National Natural Science Foundation of China (NSFC) to facilitate academic exchange and cooperation both domestically and internationally.

Study results: sMRI has identified early neurodevelopmental biomarkers in FES patients, and fMRI has highlighted functional abnormalities across disease stages. Multimodal/multiomics analysis has revealed complex brain-neurobiology interactions. Neuromodulation techniques, which directly modulate neural activity in specific brain regions, offer promising long-term benefits for stabilizing conditions and enhancing patients' quality of life. NSFC-funded analysis shows China is increasing its funding for schizophrenia research, though funding distribution remains uneven. The research focus has shifted from a single perspective on brain structure and function to multichannel, multimodal comprehensive analysis methods. This progress has driven the integration of machine learning-driven multiomics research, aiming to construct disease classification models, explore disease mechanisms, and guide treatment from multidimensional and interdisciplinary perspectives.

Conclusions: MRI technology has provided new perspectives for the diagnosis and treatment of schizophrenia, especially the neurobiological foundations of the disease. Support from the NSFC provides a scientific and financial basis for future research and treatment, heralding scientific discoveries and technological innovations in this field and bringing hope to schizophrenia patients.

Background and hypothesis: Previous studies have found that both physical inactivity and poor sleep are deleteriously associated with severe mental illness (SMI). The aim of current study was to investigate the joint association of physical activity (PA) and sleep with late-onset SMI (schizophrenia and bipolar disorder) risk.

Study design: A total of 340 187 (for schizophrenia)/340 239 (for bipolar disorder) participants without schizophrenia or bipolar disorder from the UK Biobank were included. Baseline PA levels were categorized as high, intermediate, and low according to the total volume of PA. Sleep was categorized into healthy, intermediate, and poor according to an established composited sleep score of chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. We derived 9 PA-sleep combinations, accordingly.

Study results: After an average follow-up of 13.2 years, 814 participants experienced schizophrenia and 846 participants experienced bipolar disorder. Both low PA level, intermediate, and poor sleep were independently associated with increased risk of SMI. PA level and sleep had additive and multiplicative interactions on SMI risk. Compared to those with high PA level and healthy sleep, individuals with low PA and poor sleep had the highest risk of SMI (hazard ratio: 1.95; 95% CI: 1.02-3.70, P < .001) for schizophrenia; (hazard ratio: 3.81; 95% CI: 2.35-6.15) for bipolar disorder. A higher PA level may attenuate the detrimental effects of poor sleep.

Conclusion: Both low PA and poor sleep was associated with increasing risk of late-onset SMI. Those with low PA and poor sleep had the highest risk of late-onset SMI, suggesting likely synergistic effects. Our findings supported the need to target both PA and sleep behaviors in research and clinical practice.

Background and hypothesis: Antipsychotic (AP) prescription in clinical high risk for psychosis (CHR-P) subjects remains a divisive issue. Although official guidelines currently discourage AP treatment in CHR-P, it is common in clinical practice, especially for psychosis prevention. The aim of this study was to investigate whether baseline AP need (especially in high-dose) indexes a CHR-P subgroup with poorer prognosis and differs from AP-naïve subjects in terms of sociodemographic, clinical, and outcome parameters across a 2-year follow-up.

Study design: CHR-P participants were treated within an "Early Intervention in Psychosis" program and completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale both at baseline and every 12 months. Individuals with baseline AP prescription were included in the high-dose or low-dose CHR-P-AP+ subgroup. The others were grouped as AP-naïve. Cox regression analyses and mixed-design ANOVA were performed.

Study results: 180 CHR-P individuals were enrolled (32 high-dose, 60 low-dose, and 88 AP-naïve). Compared to AP-naive, CHR-P AP+ subgroups showed older age and more severe clinical presentation. High-dose subgroup also had grater functioning decline at entry and poorer functional recovery at follow-up. No inter-group differences in psychosis transition and symptomatic remission were found. Significant improvement in clinical outcomes were found over time in all subgroups. Baseline AP prescription was specifically associated with a more relevant improvement in PANSS total score, and in negative and disorganized symptoms.

Conclusions: Our results suggest that baseline AP need is an important prognostic parameter in CHR-P and should be considered in risk/benefit calculators.

Background: Schizophrenia is conceptualized as a brain connectome disorder that can emerge as early as late childhood and adolescence. However, the underlying neurodevelopmental basis remains unclear. Recent interest has grown in children and adolescent patients who experience symptom onset during critical brain development periods. Inspired by advanced methodological theories and large patient cohorts, Chinese researchers have made significant original contributions to understanding altered brain connectome development in early-onset schizophrenia (EOS).

Study design: We conducted a search of PubMed and Web of Science for studies on brain connectomes in schizophrenia and neurodevelopment. In this selective review, we first address the latest theories of brain structural and functional development. Subsequently, we synthesize Chinese findings regarding mechanisms of brain structural and functional abnormalities in EOS. Finally, we highlight several pivotal challenges and issues in this field.

Study results: Typical neurodevelopment follows a trajectory characterized by gray matter volume pruning, enhanced structural and functional connectivity, improved structural connectome efficiency, and differentiated modules in the functional connectome during late childhood and adolescence. Conversely, EOS deviates with excessive gray matter volume decline, cortical thinning, reduced information processing efficiency in the structural brain network, and dysregulated maturation of the functional brain network. Additionally, common functional connectome disruptions of default mode regions were found in early- and adult-onset patients.

Conclusions: Chinese research on brain connectomes of EOS provides crucial evidence for understanding pathological mechanisms. Further studies, utilizing standardized analyses based on large-sample multicenter datasets, have the potential to offer objective markers for early intervention and disease treatment.

Background and hypothesis: Current treatments for schizophrenia are only partially effective, and there are no medications for negative symptoms or cognitive impairment. Neuromodulation, such as repetitive transcranial magnetic stimulation (rTMS), has potential as a novel intervention for schizophrenia. Prior to clinical use, rTMS should have demonstrated safety in a large schizophrenia population. However, the safety profile of rTMS in schizophrenia is not well characterized, and regulatory agencies have expressed concern about safety in this population.

Study design: We conducted a systematic review with meta-analysis of rTMS studies in schizophrenia. We searched PubMed, the Cochrane Library, PsycINFO, and Science Citation Index Expanded for rTMS studies in schizophrenia that reported adverse effects. We extracted the number of participants who experienced an adverse effect and calculated the prevalence of each adverse effect for active or sham rTMS. We tested the difference between the prevalence of events in the active and sham conditions. We assessed risk of bias using the Cochrane Handbook.

Study results: The initial search identified 1472 studies. After screening, 261 full-text studies were assessed, and 126 met inclusion criteria (N = 4122 total subjects). The prevalence of headache or scalp pain, dizziness or syncope, facial twitching, and nausea was higher for active rTMS compared to sham (P < .05). The prevalence of all other adverse effects, including seizure, was not different between active and sham rTMS.

Conclusions: rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure, compared to the general population.

Background and hypothesis: Redox dysregulation has been proposed as a convergent point of childhood trauma and the emergence of psychiatric disorders, such as schizophrenia (SCZ). A critical region particularly vulnerable to environmental insults during adolescence is the ventral hippocampus (vHip). However, the impact of severe stress on vHip redox states and their functional consequences, including behavioral and electrophysiological changes related to SCZ, are not entirely understood.

Study design: After exposing adolescent animals to physical stress (postnatal day, PND31-40), we explored social and cognitive behaviors (PND47-49), the basal activity of pyramidal glutamate neurons, the number of parvalbumin (PV) interneurons, and the transcriptomic signature of the vHip (PND51). We also evaluated the impact of stress on the redox system, including mitochondrial respiratory function, reactive oxygen species (ROS) production, and glutathione (GSH) levels in the vHip and serum.

Study results: Adolescent-stressed animals exhibited loss of sociability, cognitive impairment, and vHip excitatory/inhibitory (E/I) imbalance. Genome-wide transcriptional profiling unveiled the impact of stress on redox system- and synaptic-related genes. Stress impacted mitochondrial respiratory function and changes in ROS levels in the vHip. GSH and glutathione disulfide (GSSG) levels were elevated in the serum of stressed animals, while GSSG was also increased in the vHip and negatively correlated with sociability. Additionally, PV interneuron deficits in the vHip caused by adolescent stress were associated with oxidative stress.

Conclusions: Our results highlight the negative impact of adolescent stress on vHip redox regulation and mitochondrial function, which are partially associated with E/I imbalance and behavioral abnormalities related to SCZ.

Background and hypothesis: In response to Health Canada's March 2020 directive, patients on clozapine for over 12 months were allowed to extend hematological testing intervals from 4 to 8 weeks during the COVID-19 pandemic. We hypothesized that this change would not affect the timely detection of hematological abnormalities in patients with severe mental illness.

Study design: A chart review was conducted of patients at the Royal Ottawa who were prescribed clozapine from March 2019 to March 2021. We analyzed clinical and hematological data from electronic health records and Clozaril Support and Assistance Network database to compare occurrences of hematological abnormalities [leukopenia (white blood cell count <3.5 × 109/L) and agranulocytosis (absolute neutrophil count <0.5 × 109/L)] from March 17, 2020 to March 16, 2021, between standard and extended monitoring protocols using binomial logistic and zero-inflated negative binomial regressions.

Study results: Of 621 patients, 196 were on extended blood monitoring, and 425 followed standard blood monitoring. Clozapine dose did not differ between groups (standard: 370 ± 201 mg; extended: 352 ± 172 mg; P = .14, ds = 0.10). Clozapine treatment duration up to March 2021 was 12.6 ± 8.3 years, with the extended group (10 ± 7.9 years) having a significantly (P < .01, ds = 0.50) shorter duration than the standard (14 ± 8.2 years). Extended monitoring did not significantly impact likelihood of detecting hematological abnormalities (OR = 0.83, 95% CI [0.58,1.41], P = .55) after controlling for age, sex, total bloodwork, and other psychotropics associated with neutrophil counts (ie, valproate, olanzapine). No patient on the extended regimen developed agranulocytosis.

Conclusions: Reducing blood monitoring frequency in patients on clozapine for more than 12 months did not compromise detection of hematological abnormalities.

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 and hypothesis: This review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals.

Study design: The review provides an overview of the developmental history of the SHARP study and its contributions to understanding the needs of CHR individuals. It explores the limitations of traditional antipsychotic approaches and introduces PBE as a promising framework for intervention.

Study results: Three key interventions implemented by the SHARP team are discussed: nutritional supplementation based on niacin skin response blunting, precision transcranial magnetic stimulation targeting cognitive and brain functional abnormalities, and cognitive behavioral therapy for psychotic symptoms addressing symptomatology and impaired insight characteristics. Each intervention is evaluated within the context of PBE, emphasizing the potential for tailored approaches to CHR individuals.

Conclusions: The review highlights the strengths and clinical applications of the discussed interventions, underscoring their potential to revolutionize preventive care for CHR individuals. It also provides insights into future directions for PBE in CHR populations, including efforts to expand evaluation techniques and enhance precision in interventions.