Schizophrenia Bulletin最新文献

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Brain Age Disparities in Psychosis Across DSM Diagnoses and B-SNIP Biotypes DSM诊断和B-SNIP生物型在精神病中的脑年龄差异
IF 6.6 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-31 DOI: 10.1093/schbul/sbaf022
Liisi Promet, Shashwath A Meda, Ney Alliey-Rodriguez, Brett A Clementz, Elliott S Gershon, Scot K Hill, Elena I Ivleva, Sarah K Keedy, Matcheri S Keshavan, Jennifer E McDowell, David A Parker, Carol A Tamminga, Godfrey D Pearlson
{"title":"Brain Age Disparities in Psychosis Across DSM Diagnoses and B-SNIP Biotypes","authors":"Liisi Promet, Shashwath A Meda, Ney Alliey-Rodriguez, Brett A Clementz, Elliott S Gershon, Scot K Hill, Elena I Ivleva, Sarah K Keedy, Matcheri S Keshavan, Jennifer E McDowell, David A Parker, Carol A Tamminga, Godfrey D Pearlson","doi":"10.1093/schbul/sbaf022","DOIUrl":"https://doi.org/10.1093/schbul/sbaf022","url":null,"abstract":"Background and Hypothesis The brain age gap (BAG) quantifies the difference between predicted brain age and chronological age. Prior research implicates higher BAG in psychotic disorders, suggesting accelerated brain aging. We hypothesized distinct brain aging profiles among biological subtypes of psychosis and intermediate BAG in their relatives. Study Design Brain age gap values were quantified in 348 healthy controls (HCs), 950 psychosis probands classified by both DSM diagnoses of psychotic bipolar disorder, type I (BP, n = 247), schizoaffective disorder (SAD, n = 313), and schizophrenia (SZ, n = 390), and Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Biotypes (301 Biotype 1, 304 Biotype 2, and 345 Biotype 3), and 491 of their non-psychotic first-degree relatives. We calculated brain age values from structural T1-weighted images using the pre-trained, open-source brain age package, brainageR. In probands, we assessed associations between BAG and clinical characteristics, comorbid disorders, medications, and polygenic risk scores for SZ (PRS-SZ). Study Results All DSM diagnosis and Biotype groups had higher BAG than HC. While no significant differences were observed between BP, SAD, or SZ, Biotypes 1 and 2 had significantly higher BAG compared to Biotype 3. Relatives exhibited intermediate BAG values between HC and probands, with the highest BAG in relatives of those with SAD. Brain age gap was not linked to comorbid disorders or PRS-SZ, but was associated with symptom severity, cognition, functioning, and psychotropic medication use. Conclusions Bipolar-Schizophrenia Network for Intermediate Phenotypes Biotypes better captured age-related brain structural differences in psychosis than DSM diagnoses. Associations between BAG and medication underscore the potential influence of pharmacotherapy on brain aging in psychosis.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"49 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Social Defeat and Psychosis in the United States: A Replication and Critical Reconceptualization. 美国的社会失败与精神病:复制与批判性的再概念化。
IF 5.3 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-29 DOI: 10.1093/schbul/sbaf081
Jacqueline I Cosse, Brianna J Amos, Luisa Prout, Dget L Downey, Seonyeong Kim, Stephanie Secaira, Lisa Fedina, Jordan E DeVylder
{"title":"Social Defeat and Psychosis in the United States: A Replication and Critical Reconceptualization.","authors":"Jacqueline I Cosse, Brianna J Amos, Luisa Prout, Dget L Downey, Seonyeong Kim, Stephanie Secaira, Lisa Fedina, Jordan E DeVylder","doi":"10.1093/schbul/sbaf081","DOIUrl":"https://doi.org/10.1093/schbul/sbaf081","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>The social defeat hypothesis posits that exclusion and discrimination experienced by socially marginalized populations predict psychotic experiences (PEs), particularly when perceived as defeatist. However, its emphasis on individual-level factors may obscure the role of structural and systemic influences. This is significant for the US context, given US histories of pronounced structural racism and economic inequality. This study extends the social defeat hypothesis by examining established indicators of social defeat, along with US-specific factors that capture structural influences on individuals' perceptions of discrimination and exclusion as defeatist.</p><p><strong>Design: </strong>Data from the National Survey of Poly-victimization and Mental Health (N = 1 584) were analyzed to investigate cross-sectional associations between individual-level and structural indicators of marginalization and social defeat and self-reported PEs among young adults.</p><p><strong>Study results: </strong>BIPOC participants had 60% higher odds of reporting PEs in the past year (OR = 1.60; 95% CI, 1.27-2.03; P = .003). Furthermore, participants with at least 1 experience of police violence in the past year have 52% higher odds of reporting PEs (OR = 1.52; 95% CI, 1.16-2.00; P = .003). Several additional indicators were associated with increased odds of PE, including race (non-White compared to White), high-frequency substance use, everyday discrimination, exposure to childhood abuse or bullying.</p><p><strong>Conclusions: </strong>Findings align with European social defeat literature, confirming the relevance of the hypothesis in the US context. However, prominence of structural factors (racism, police violence) suggests that the social defeat hypothesis should incorporate systemic influences, emphasizing the need for interventions addressing societal contributors to psychosis risk.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antipsychotic Discontinuation and Re-initiation in Pregnant Women With Schizophrenia: A Retrospective Cohort Study From South Korea 韩国一项回顾性队列研究:精神分裂症孕妇的抗精神病药物停药和重新服用
IF 6.6 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-28 DOI: 10.1093/schbul/sbaf077
Jiyeon Kim, Julia Kaminska, Ye-Jee Kim, Sung Woo Joo, Bo Ram Yang
{"title":"Antipsychotic Discontinuation and Re-initiation in Pregnant Women With Schizophrenia: A Retrospective Cohort Study From South Korea","authors":"Jiyeon Kim, Julia Kaminska, Ye-Jee Kim, Sung Woo Joo, Bo Ram Yang","doi":"10.1093/schbul/sbaf077","DOIUrl":"https://doi.org/10.1093/schbul/sbaf077","url":null,"abstract":"Background and Hypothesis Pregnant women with schizophrenia are more likely to discontinue treatment, which could trigger a relapse of symptoms. However, data on patterns and risk factors related to antipsychotic discontinuation and re-initiation in Asian pregnant women are insufficient. Study Design We conducted a retrospective cohort study using a nationwide Korean database. The pregnancy group included women who had received antipsychotics before pregnancy and was matched 1:2 with a non-pregnancy group. Using Kaplan–Meier curves, we assessed discontinuation patterns during pregnancy and re-initiation patterns among those who discontinued treatment within the first trimester. A Cox proportional hazards regression analysis was used to examine factors associated with first-trimester discontinuation and re-initiation among those who discontinued during this period. Study Results Pregnant women (n = 2066) had a significantly higher risk of discontinuation than did non-pregnant women (adjusted hazard ratio 3.09; 95% confidence interval 2.85–3.34). Within the first trimester, 67.5% of pregnant women (n = 1394) discontinued antipsychotic use. Women aged 25–29 years were more likely to discontinue (1.25; 1.07–1.47). Among first-trimester discontinuers, 35.2% (n = 491) re-initiated treatment before delivery. A longer duration of antipsychotic use (1.60; 1.06–2.42) and higher daily doses (2.47; 1.76–3.45) were associated with re-initiation of antipsychotics. Conclusions We revealed that most pregnant women discontinued schizophrenia treatment, but those using higher cumulative doses had a higher likelihood of re-initiation. Our findings imply that treatment decisions for pregnant women should consider various clinical factors, including the history of prescriptions and obstetric characteristics. Moreover, these patients require close monitoring after discontinuation.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"10 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Severe Outcomes and Length of Stay Among People With Schizophrenia Hospitalized for COVID-19: A Population-Based Retrospective Cohort Study 因COVID-19住院的精神分裂症患者的严重结局和住院时间:一项基于人群的回顾性队列研究
IF 6.6 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-28 DOI: 10.1093/schbul/sbaf066
Jessica Gronsbell, John Wang, Hilary Thurston, Jianhui Gao, Yaqi Shi, Anthony D Train, Debra Butt, Andrea Gershon, Braden O’Neill, Karen Tu
{"title":"Severe Outcomes and Length of Stay Among People With Schizophrenia Hospitalized for COVID-19: A Population-Based Retrospective Cohort Study","authors":"Jessica Gronsbell, John Wang, Hilary Thurston, Jianhui Gao, Yaqi Shi, Anthony D Train, Debra Butt, Andrea Gershon, Braden O’Neill, Karen Tu","doi":"10.1093/schbul/sbaf066","DOIUrl":"https://doi.org/10.1093/schbul/sbaf066","url":null,"abstract":"Background Schizophrenia is associated with substantial physical and psychiatric comorbidities that increase the risk of severe outcomes in COVID-19 infection. However, few studies have examined the differences in care and outcomes among people with schizophrenia throughout the pandemic. We hypothesized that rates of in-hospital mortality, admission to the intensive care unit (ICU), and length of stay differed among people with and without schizophrenia. Study design We conducted a population-based retrospective cohort study using administrative health data from Ontario, Canada, which included individuals hospitalized for COVID-19 between February 2020 and October 2023. We compared mortality, ICU admission, and length of stay using regression models adjusted for age, sex, comorbidities, vaccination status, and sociodemographic characteristics. Study results We evaluated 66 959 hospital admissions, 4.3% (2884) of which involved people with schizophrenia. People with schizophrenia had a significantly decreased rate of ICU admission (adjusted Odds Ratio [OR]: 0.74 [0.67, 0.82]), a longer length of stay (adjusted RR: 1.25 [1.21, 1.30]), but a similar risk of mortality (adjusted OR: 1.09 [0.98, 1.22]) as people without schizophrenia. Age modified the relationship between schizophrenia and ICU admission. People with schizophrenia aged 60-75 were substantially less likely to be admitted to the ICU relative to those without (18.4% vs 26.5%, P &amp;lt; .001). Conclusions Our findings underscore disparities in care among people with and without schizophrenia. These disparities vary by age and suggest that people with schizophrenia may not be receiving the same level of care as people without schizophrenia hospitalized for COVID-19.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"83 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prebiotics Rescue Gut Microbiome Dysregulation and Enhance Cognitive and Gastrointestinal Function in a Mouse Model of Schizophrenia. 益生元在精神分裂症小鼠模型中拯救肠道微生物失调并增强认知和胃肠功能。
IF 5.3 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-28 DOI: 10.1093/schbul/sbaf056
Carolina Gubert, Geraldine Kong, Sheida Shadani, Sasha Connell, Bethany A Masson, Nicholas van de Garde, Vinod K Narayana, Thibault Renoir, Anthony J Hannan
{"title":"Prebiotics Rescue Gut Microbiome Dysregulation and Enhance Cognitive and Gastrointestinal Function in a Mouse Model of Schizophrenia.","authors":"Carolina Gubert, Geraldine Kong, Sheida Shadani, Sasha Connell, Bethany A Masson, Nicholas van de Garde, Vinod K Narayana, Thibault Renoir, Anthony J Hannan","doi":"10.1093/schbul/sbaf056","DOIUrl":"https://doi.org/10.1093/schbul/sbaf056","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Schizophrenia is a devastating psychiatric disorder characterized by positive (eg, hallucinations) and negative (eg, reduced motivation) symptoms, and cognitive deficits. Chronic gastrointestinal tract issues exist as comorbid symptoms of schizophrenia. Recent findings indicate the involvement of the microorganisms that inhabit the gut, the microbiota (and the broader microbiome which also includes microbial genomes, etc.) in schizophrenia pathogenesis. In the present study, we hypothesized that chronic administration with prebiotics fructooligosaccharide and galactooligosaccharide (FOS and GOS; a combination used clinically for other disorders) would restore gut microbiome composition of the metabotropic glutamate receptor 5 (mGlu5) knockout (KO) mouse model of schizophrenia, which we previously demonstrated to exhibit gut dysbiosis.</p><p><strong>Study design: </strong>We assessed the impact of prebiotics on gut microbiome composition and function, as well as the gastrointestinal function and schizophrenia-like phenotype of mGlu5 KO mice and wild-type littermates. We administered a combination of the prebiotics FOS and GOS, vs vehicle control administration, in both the mouse model of schizophrenia and wild-type littermates.</p><p><strong>Study results: </strong>The present study firstly corroborated the altered gut microbiome composition in the mGlu5 KO mouse model of schizophrenia. Importantly, we have revealed an altered microbial metabolic profile. We have also shown that the prebiotics we administered were not only able to rescue these gut microbiome changes but also had additional beneficial effects including cognitive enhancement and improved gastrointestinal function.</p><p><strong>Conclusion: </strong>These preclinical findings indicate that prebiotics, such as the combination of FOS and GOS used in the present study, may have therapeutic potential in schizophrenia as an add-on intervention with an exceptional safety profile.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Delineating the Transmission of Subthreshold Psychosis Symptoms Across Generations: The Philadelphia Family Neurodevelopmental Cohort 描述阈下精神病症状的代际传递:费城家族神经发育队列
IF 6.6 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-27 DOI: 10.1093/schbul/sbaf074
Lauren K White, Monica E Calkins, Megan M Himes, Tyler M Moore, Ruben C Gur, Ran Barzilay, Raquel E Gur
{"title":"Delineating the Transmission of Subthreshold Psychosis Symptoms Across Generations: The Philadelphia Family Neurodevelopmental Cohort","authors":"Lauren K White, Monica E Calkins, Megan M Himes, Tyler M Moore, Ruben C Gur, Ran Barzilay, Raquel E Gur","doi":"10.1093/schbul/sbaf074","DOIUrl":"https://doi.org/10.1093/schbul/sbaf074","url":null,"abstract":"Background and Hypothesis Intergenerational factors are implicated in development of schizophrenia spectrum disorders. Studying psychosis spectrum (PS) symptoms dimensionally in a longitudinal, prospective intergenerational cohort can provide crucial insight into risk pathways. Thus, we established the Philadelphia Family Neurodevelopmental Cohort (PFNC), an intergenerational study that follows Philadelphia Neurodevelopmental Cohort (PNC) participants as they transition to parenthood, along with their offspring. This first report describes the creation of the PFNC, followed by an examination of longitudinal associations between risk factors assessed in adolescence (PS symptoms, cognition, and traumatic life events) and mental health and resilience outcomes in parenthood. Study Design Since the PNC was accrued (2009-2011; ages 8-21 years), many participants have become parents. As an initial step in the development of PFNC, participants completed a virtual self-report battery to assess parental status, family structure, current mental health symptoms, and parent-relevant risk and resilience factors. Study Results The current PFNC includes 456 PNC participants with 740 offspring, consisting primarily of biological mothers (female = 84%; Black = 65%; mean parent age = 28.38 years, SD = 3.40; mean offspring age = 4.01 years, SD = 3.36). Findings revealed adolescent PS symptoms and traumatic events are associated with PS symptoms in parenthood. Adolescent PS symptoms were also linked to higher levels of household chaos approximately 12 years later. Conclusion Despite the growing recognition of the intergenerational transmission of neuropsychiatric risk, there is limited research examining intergenerational risk factors in the context of PS symptoms. The PFNC represents a critical next step toward advancing our understanding of intergenerational pathways contributing to PS risk.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"4 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advancing Understanding of Treatment Response in Schizophrenia With Psychosis Using a Novel Dynamic Reward Task 利用一种新的动态奖励任务促进对精神分裂症合并精神病治疗反应的理解
IF 6.6 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-27 DOI: 10.1093/schbul/sbaf070
Ju-Chun Pei, Chia-Yuan Chang, Ya-Wen Liu, Ching Chen, Ching-Yi Liu, Ming H Hsieh, Chih-Min Liu, Wen-Sung Lai
{"title":"Advancing Understanding of Treatment Response in Schizophrenia With Psychosis Using a Novel Dynamic Reward Task","authors":"Ju-Chun Pei, Chia-Yuan Chang, Ya-Wen Liu, Ching Chen, Ching-Yi Liu, Ming H Hsieh, Chih-Min Liu, Wen-Sung Lai","doi":"10.1093/schbul/sbaf070","DOIUrl":"https://doi.org/10.1093/schbul/sbaf070","url":null,"abstract":"Background and Hypothesis Schizophrenia presents significant treatment challenges, particularly due to medication resistance observed in some patients receiving antipsychotics. Emerging research suggests a potential link between impaired reinforcement learning, the severity of psychotic symptoms, and dopamine system abnormalities. Exploring reinforcement learning in therapeutic settings could provide critical insights into the efficacy of antipsychotic treatments. This study aimed to investigate whether neurocognitive profiles, specifically choice strategies and model fitting parameters assessed using the Dynamic Reward Task (DRT), could provide insights into treatment response variability among patients with schizophrenia. Study Design We conducted a comprehensive neurocognitive assessment on chronic schizophrenia patients experiencing psychotic relapse, categorized by treatment response (high-response vs low-response). Participants underwent DRT, Wisconsin Card Sorting Test (WCST), and Continuous Performance Test (CPT) to evaluate reward processing, executive function, and sustained attention, respectively. We employed statistical analyses to compare task performance between groups and assess changes before and after antipsychotic treatment. Study Results We identified significant differences in treatment effects across different response groups in DRT scores, choice strategies, and model-fitting parameters. Conversely, all schizophrenia groups had consistent abnormalities on the WCST and CPT evaluations compared to controls. Conclusions Our findings highlight the efficacy of DRT, WCST, and CPT in delineating neurocognitive profiles relevant to treatment response in schizophrenia. Specifically, the DRT effectively differentiated between high- and low-response patients. Distinct deficits in reward processing and executive function identified here may serve as potential indicators, informing personalized treatment strategies tailored to individual responses to antipsychotic medication.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"83 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
"Schizophrenia, Consciousness, and the Self" Twenty Years Later: Revisiting the Ipseity-Disturbance Model and the Developmental Nature of Self-Disorder in the Schizophrenia Spectrum. “精神分裂症,意识和自我”二十年后:重新审视精神分裂症谱系中易激-障碍模型和自我障碍的发展本质。
IF 5.3 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-25 DOI: 10.1093/schbul/sbaf071
Andrea Raballo, Mads Gram Henriksen, Michele Poletti, Josef Parnas
{"title":"\"Schizophrenia, Consciousness, and the Self\" Twenty Years Later: Revisiting the Ipseity-Disturbance Model and the Developmental Nature of Self-Disorder in the Schizophrenia Spectrum.","authors":"Andrea Raballo, Mads Gram Henriksen, Michele Poletti, Josef Parnas","doi":"10.1093/schbul/sbaf071","DOIUrl":"https://doi.org/10.1093/schbul/sbaf071","url":null,"abstract":"<p><p>Self-disorders (SD) designate a pattern of non-psychotic anomalous self-experiences, which specifically aggregate in clinical and subclinical forms of schizophrenia spectrum disorders (SSD), including familial high-risk configurations. SD have been corroborated as a valuable, quantitatively tractable, trait phenotype for indexing genetic liability to SSD, and, as a risk phenotype, they offer critical insights into the nature of these complex conditions which precede and shape the development of more overt clinical manifestations (including schizotypal features and positive, negative, and disorganized symptoms). In the last three decades, the concept of self-disorders has evolved from early clinical observations to a well-defined research domain, offering a nuanced understanding of schizophrenia spectrum vulnerabilities and holding promise for improving diagnostic accuracy, enhancing prognostic assessments, offering novel targets for intervention, and advancing our understanding of the schizophrenia spectrum.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Schizophrenia-Related Synaptic Dysfunction and Abnormal Sensorimotor Gating in Akap11-Deficient Mice akap11缺失小鼠中与精神分裂症相关的突触功能障碍和异常感觉运动门控
IF 6.6 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-23 DOI: 10.1093/schbul/sbaf055
Ya-Qi Zhang, Xin Cai, Qing Zhang, Mei-Yu Yin, Yingqi Guo, Cong Li, Guolan Ma, Lu Wang, Hong Chang, Xiao Xiao, Shi-Wu Li, Ming Li
{"title":"Schizophrenia-Related Synaptic Dysfunction and Abnormal Sensorimotor Gating in Akap11-Deficient Mice","authors":"Ya-Qi Zhang, Xin Cai, Qing Zhang, Mei-Yu Yin, Yingqi Guo, Cong Li, Guolan Ma, Lu Wang, Hong Chang, Xiao Xiao, Shi-Wu Li, Ming Li","doi":"10.1093/schbul/sbaf055","DOIUrl":"https://doi.org/10.1093/schbul/sbaf055","url":null,"abstract":"Background and Hypothesis Large-scale whole exome sequencing (WES) analyses have implicated rare protein-truncating variants (PTVs) in the AKAP11 gene contributing to schizophrenia risk. Previous studies reported alterations of EEG characteristics and synaptic proteome in Akap11 mutant mice. We hypothesize that synaptic dysfunction contributes to AKAP11 deficiency in the pathogenesis of schizophrenia. Study Design We generated an Akap11 knockout mouse and employed a series of behavioral evaluations, neuronal sparse labeling assays, electron microscopy, and immunoprecipitation mass spectrometry (IP-MS) to elucidate the impacts of Akap11 on schizophrenia-relevant phenotypes. Study Results Our behavioral paradigm evaluations revealed that Akap11 deficient mice exhibited impaired prepulse inhibition and anxiety-like behaviors compared with their wild-type littermates. Neuronal sparse labeling assays indicated a significant reduction in the density of total and thin spines in Akap11 deficient mice, and ultrastructural analysis via electron microscopy disclosed marked alterations in synaptogenesis after suppressing Akap11, including the reduced density of typical synapses, synaptic vesicle density, and postsynaptic density (PSD) length. IP-MS identified 222 high-confidence interaction proteins of Akap11, encompassing synapses-related proteins (eg, Exoc4, Ncam1, Picalm, Vapb) and actin-related proteins (Actb, Diaph1), and enrichment analyses further showed that Akap11 may contribute to RNA splicing, extracellular matrix organization, axon guidance, post-NMDA receptor activation events, GPER1 signaling and PKA activation pathways. Conclusions Together, these findings delineated the synaptic and behavioral phenotypes in Akap11 deficient mice, shedding light on the potential mechanisms underlying the role of rare PTVs in schizophrenia and substantiating the significance of AKAP11 as a risk gene for this illness.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"22 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective. 修正:n -甲基-d-天冬氨酸受体拮抗剂对精神分裂症和早期精神病患者听觉刺激时γ -带活动的影响与脑电/磁图数据的比较:系统回顾和观点。
IF 5.3 1区 医学
Schizophrenia Bulletin Pub Date : 2025-05-22 DOI: 10.1093/schbul/sbaf082
{"title":"Correction to: Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective.","authors":"","doi":"10.1093/schbul/sbaf082","DOIUrl":"https://doi.org/10.1093/schbul/sbaf082","url":null,"abstract":"","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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