Schizophrenia (Heidelberg, Germany)最新文献

{"title":"A generalisability theory approach to quantifying changes in psychopathology among ultra-high-risk individuals for psychosis.","authors":"Zohreh Doborjeh, Oleg N Medvedev, Maryam Doborjeh, Balkaran Singh, Alexander Sumich, Sugam Budhraja, Wilson Wen Bin Goh, Jimmy Lee, Margaret Williams, Edmund M-K Lai, Nikola Kasabov","doi":"10.1038/s41537-024-00503-y","DOIUrl":"10.1038/s41537-024-00503-y","url":null,"abstract":"<p><p>Distinguishing stable and fluctuating psychopathological features in young individuals at Ultra High Risk (UHR) for psychosis is challenging, but critical for building robust, accurate, early clinical detection and prevention capabilities. Over a 24-month period, 159 UHR individuals were assessed using the Positive and Negative Symptom Scale (PANSS). Generalisability Theory was used to validate the PANSS with this population and to investigate stable and fluctuating features, by estimating the reliability and generalisability of three factor (Positive, Negative, and General) and five factor (Positive, Negative, Cognitive, Depression, and Hostility) symptom models. Acceptable reliability and generalisability of scores across occasions and sample population were demonstrated by the total PANSS scale (Gr = 0.85). Fluctuating symptoms (delusions, hallucinatory behaviour, lack of spontaneity, flow in conversation, emotional withdrawal, and somatic concern) showed high variability over time, with 50-68% of the variance explained by individual transient states. In contrast, more stable symptoms included excitement, poor rapport, anxiety, guilt feeling, uncooperativeness, and poor impulse control. The 3-factor model of PANSS and its subscales showed robust reliability and generalisability of their assessment scores across the UHR population and evaluation periods (G = 0.77-0.93), offering a suitable means to assess psychosis risk. Certain subscales within the 5-factor PANSS model showed comparatively lower reliability and generalisability (G = 0.33-0.66). The identified and investigated fluctuating symptoms in UHR individuals are more amendable by means of intervention, which could have significant implications for preventing and addressing psychosis. Prioritising the treatment of fluctuating symptoms could enhance intervention efficacy, offering a sharper focus in clinical trials. At the same time, using more reliable total scale and 3 subscales can contribute to more accurate assessment of enduring psychosis patterns in clinical and experimental settings.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"87"},"PeriodicalIF":3.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The need for open access MRI in psychosis: introducing a new global imaging resource (PsyShareD).","authors":"Simon L Evans, Paul Allen","doi":"10.1038/s41537-024-00501-0","DOIUrl":"10.1038/s41537-024-00501-0","url":null,"abstract":"","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"85"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular targets of fingolimod and siponimod for treating the impaired cognition of schizophrenia using network pharmacology and molecular docking.","authors":"Chao Li, Chuanjun Zhuo, Xiaoyan Ma, Ranli Li, Ximing Chen, Yachen Li, Qiuyu Zhang, Lei Yang, Lina Wang","doi":"10.1038/s41537-024-00504-x","DOIUrl":"10.1038/s41537-024-00504-x","url":null,"abstract":"<p><p>The treatment of cognitive impairment in schizophrenia is an unaddressed need due to the absence of novel treatments. Recent studies demonstrated that fingolimod and siponimod have neuroprotective effects in several neuropsychiatric disorders; however, their pharmacological mechanisms are unclear. The objective of this study was to identify potential molecular mechanisms of fingolimod and siponimod for improving cognition of schizophrenia through network pharmacology and molecular docking. The putative target genes of ingredients, schizophrenia, and impaired cognition were obtained from online databases, including SwissTargetPrediction, PharmMapper, GeneCards, CTD, DisGeNET, and OMIM. A protein-protein interaction network was constructed to identify core targets. The DAVID database was used for GO and KEGG pathway enrichment analyses. An ingredient-target-pathway-disease network was constructed using Cytoscape. Finally, the interactions between ingredients and core targets were assessed with molecular docking. The analysis revealed 260 targets shared by fingolimod and siponimod, 257 unique targets for fingolimod, and 88 unique targets for siponimod. Two signaling pathways were involved in fingolimod-mediated improvements in the cognition of schizophrenia, including the PI3K-Akt and MAPK signaling pathways. The core targets that regulated these two pathways included IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF. The MAPK signaling pathway was involved in siponimod-mediated improvement in the cognition of schizophrenia. The MAPK pathway was regulated by three core targets, namely TNF, AKT1, and CASP3. Docking scores ranged from -5.0 to -10.4 kcal/mol. Our analysis revealed that fingolimod regulates the PI3K-Akt and MAPK signaling pathways via the core targets IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF, and siponimod regulates the MAPK signaling pathways via the core targets AKT1, TNF, and CASP3 to improve the cognition of schizophrenia. Our results provide potential targets and a theoretical basis for the design of new drugs to treat the impaired cognition of schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"80"},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and functional outcomes at 7-year follow-up of children presenting putative antecedents of schizophrenia at age 9-12 years.","authors":"Alexis E Cullen, Ruth E Roberts, Helen L Fisher, Kristin R Laurens","doi":"10.1038/s41537-024-00507-8","DOIUrl":"10.1038/s41537-024-00507-8","url":null,"abstract":"<p><p>Identification of youth presenting early risk factors for psychosis may facilitate preventive intervention. Through school-based screening, we recruited 112 children aged 9-12 years who presented multiple putative antecedents of schizophrenia (ASz), a family history of schizophrenia (FHx), or neither of these risk factors (typically-developing; TD). Clinical and functional outcomes were assessed at age 17-21 years (N = 93). Compared to the TD group, the ASz group had higher total Prodromal Questionnaire (PQ) scores (β = 10.59, 95% CI = 3.76, 17.42) and total psychopathology scores (β = 6.13, 95% CI: 1.03, 11.23), were more likely to score above-threshold on the PQ positive symptoms scale (OR = 4.00, 95% CI = 1.08, 14.83), and had lower scores on the Social and Occupational Functioning Scale (β = -9.43, 95% CI = -15.08, -3.77) at follow-up. The FHx and TD groups did not differ on any outcome. Findings suggest that population screening for putative antecedents of schizophrenia may identify children who would benefit from preventative intervention.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"83"},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dimensional structure of the Positive and Negative Syndrome Scale in first-episode schizophrenia spectrum disorders: an Exploratory Graph Analysis from the OPTiMiSE trial.","authors":"Francesco Dal Santo, María Paz García-Portilla, Emilio Fernández-Egea, Leticia González-Blanco, Pilar A Sáiz, Giulia Maria Giordano, Silvana Galderisi, Julio Bobes","doi":"10.1038/s41537-024-00499-5","DOIUrl":"10.1038/s41537-024-00499-5","url":null,"abstract":"<p><p>The Positive and Negative Syndrome Scale (PANSS) is the most widely used rating scale to assess psychotic symptoms in patients with schizophrenia and other primary psychoses. However, a definitive consensus regarding its dimensional structure remains elusive. The present work aims to determine the number of dimensions of the scale through a network analysis approach in a sample of individuals experiencing first-episode schizophrenia spectrum disorder (FE-SSD) with minimal or no prior exposure to antipsychotic treatment. Baseline data of 446 participants (age 25.96 ± 5.99 years, 70% males) enrolled in the OPTiMiSE trial were analysed. Exploratory Graph Analysis (EGA) was conducted to evaluate the dimensionality of the PANSS, and a bootstrap approach (bootEGA) was employed to assess model stability. The analysis was replicated, excluding unstable items with stability values below 0.75, until a stable model was achieved. The analysis of the 30 items of the PANSS revealed inadequate structural consistency, resulting in the exclusion of 9 unstable items. The final model comprised 21 symptoms distributed across four communities (Positive, Cognitive/Disorganised, Excited/Aggressive and Negative) but lacked a depressive domain. In conclusion, we propose a concise version of the PANSS, incorporating 21 items, to better assess the core symptoms of the first episode of SSD. This revised version provides clinicians with a robust psychometric tool with reduced administration time, but the complementary administration of a dedicated instrument for evaluating affective symptoms is advisable.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"81"},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling expressing features of surface proteins on single-exosome in first-episode Schizophrenia patients: a preliminary study.","authors":"Sijie Zhang, Aijun Liao, Yujue Wang, Qian Liu, Lijun Ouyang, Huiqing Peng, Liu Yuan, Linlin Zhao, Xinbo Yang, Xiaogang Chen, Ying He, Zongchang Li","doi":"10.1038/s41537-024-00510-z","DOIUrl":"10.1038/s41537-024-00510-z","url":null,"abstract":"<p><p>Proximity barcoding assay, a high-throughput method for single-exosome analysis, was employed to profile surface proteins on individual exosomes of SCZ patients. This analysis identified five differentially expressed proteins (DEPs) between SCZ patients and healthy controls (HC) and six DEPs between antipsychotic responders and non-responders. Furthermore, two exosome clusters were found to be associated with SCZ, and certain DEPs were correlated with cognitive functions.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"84"},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irregularity of visual motion perception and negative symptoms in schizophrenia.","authors":"Yi Fan, Yunhai Tao, Jue Wang, Yuan Gao, Wei Wei, Chanying Zheng, Xiaotong Zhang, Xue Mei Song, Georg Northoff","doi":"10.1038/s41537-024-00496-8","DOIUrl":"10.1038/s41537-024-00496-8","url":null,"abstract":"<p><p>Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"82"},"PeriodicalIF":3.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hierarchical analysis of the sense of agency in schizophrenia: motor control, control detection, and self-attribution.","authors":"Hiroki Oi, Wen Wen, Acer Yu-Chan Chang, Hiroyuki Uchida, Takaki Maeda","doi":"10.1038/s41537-024-00512-x","DOIUrl":"10.1038/s41537-024-00512-x","url":null,"abstract":"<p><p>The sense of agency refers to the feeling of initiating and controlling one's actions and their resulting effects on the external environment. Previous studies have uncovered behavioral evidence of excessive self-attribution and, conversely, a reduction in the sense of agency in patients with schizophrenia. We hypothesize that this apparent paradox is likely to result from impairment in lower-level processes underlying the sense of agency, combined with a higher-level compensational bias. The present study employed three behavioral tasks utilizing the same stimuli and experimental design to systematically evaluate multiple factors that influence the sense of agency, including motor control, sensorimotor processing, and self-attribution. Participants' real-time mouse movements were combined with prerecorded motions of others in ratios of 30/70, 55/45, or 80/20, with an additional angular bias of either 0° or 90°. Twenty-six patients with schizophrenia and 27 health control volunteers participated in the three tasks. Patients with schizophrenia performed significantly worse in the reaching and control detection tasks than healthy controls. However, their self-attribution in the control judgment task was comparable to that of the healthy controls. Patients with schizophrenia were impaired in motor control components and in the detection of control using sensorimotor information, but their evaluation of agency remained relatively less affected. This underscores the importance of distinguishing between different subcomponents when addressing the abnormal sense of agency in patients with schizophrenia. Subsequent cluster analysis revealed that the combined task performance accurately distinguished between the patients and healthy control participants.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"79"},"PeriodicalIF":3.0,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher Correction: Structural and functional connectivity in relation to executive functions in antipsychotic-naïve patients with first episode schizophrenia.","authors":"Tina D Kristensen, Karen S Ambrosen, Jayachandra M Raghava, Warda T Syeda, Thijs Dhollander, Cecilie K Lemvigh, Kirsten B Bojesen, Anita D Barber, Mette Ø Nielsen, Egill Rostrup, Christos Pantelis, Birgitte Fagerlund, Birte Y Glenthøj, Bjørn H Ebdrup","doi":"10.1038/s41537-024-00500-1","DOIUrl":"10.1038/s41537-024-00500-1","url":null,"abstract":"","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"77"},"PeriodicalIF":3.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene expression changes in Brodmann's Area 46 differentiate epidermal growth factor and immune system interactions in schizophrenia and mood disorders.","authors":"Tharini Ketharanathan, Avril Pereira, Suresh Sundram","doi":"10.1038/s41537-024-00488-8","DOIUrl":"10.1038/s41537-024-00488-8","url":null,"abstract":"<p><p>How early in life stress-immune related environmental factors increase risk predisposition to schizophrenia remains unknown. We examined if pro-inflammatory changes perturb the brain epidermal growth factor (EGF) system, a system critical for neurodevelopment and mature CNS functions including synaptic plasticity. We quantified genes from key EGF and immune system pathways for mRNA levels and eight immune proteins in post-mortem dorsolateral prefrontal (DLPFC; Brodmann's Area (BA) 46) and orbitofrontal (OFC; BA11) cortices from people with schizophrenia, mood disorders and neurotypical controls. In BA46, 64 genes were differentially expressed, predominantly in schizophrenia, where attenuated expression of the MAPK-ERK, NRG1-PI3K-AKT and mTOR cascades indicated reduced EGF system signalling, and similarly diminished immune molecular expression, notably in TLR, TNF and complement pathways, along with low NF-κB1 and elevated IL12RB2 protein levels were noted. There was nominal evidence for altered convergence between ErbB-PI3K-AKT-mTOR and TLR pathways in BA46 in schizophrenia. Comparatively minimal changes were noted in BA11. Overall, distinct pathway gene expression changes may reflect variant pathological processes involving immune and EGF system signalling between schizophrenia and mood disorder, particularly in DLPFC. Further, the abnormal convergence between innate immune signalling and candidate EGF signalling pathways may indicate a pathologically important interaction in the developing brain in response to environmental stressors.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"76"},"PeriodicalIF":3.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}