Schizophrenia (Heidelberg, Germany)最新文献

{"title":"The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation.","authors":"Zhenlei Peng, Qiyu Jia, Junxiong Mao, Shijie Jiang, Qi Ma, Xiao Luo, Zhiguo An, Anqi Huang, Chuang Ma, Qizhong Yi","doi":"10.1038/s41537-025-00555-8","DOIUrl":"10.1038/s41537-025-00555-8","url":null,"abstract":"<p><p>Oxidative stress (OS) is crucial in schizophrenia (SCZ) pathology. Ferroptosis, a recently discovered cell death pathway linked to OS, might contribute to the development of SCZ. This study investigated the association between ferroptosis markers and cognitive impairments in chronic SCZ patients. A retrospective analysis was conducted on 204 chronic SCZ patients with cognitive deficits and 216 healthy controls (HC) matched for relevant characteristics. Plasma levels of ferroptosis and OS markers, including iron, ferritin (FE), transferrin (TF), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), glutathione (GSH), sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured. Standardized assessments like the positive and negative syndrome scale (PANSS), and Montreal Cognitive Assessment (MoCA) were used to evaluate psychiatric symptoms, and cognitive function. SCZ patients showed significant differences in markers compared to the HC group (P < 0.01). Multiple linear regression analysis revealed that decreased GSH and iron levels, along with elevated SOD levels, were significantly associated with the overall severity of psychiatric symptoms. Additionally, reduced GPX4 levels and increased ACSL4 and FE levels were significantly linked to negative symptoms and cognitive impairments. Notably, GPX4 emerged as a key predictor for cognitive function in abstraction and language domains. Our study revealed alterations in the altered plasma levels of GPX4, GSH, iron, ACSL4, FE, and SOD in chronic SCZ patients, which might indicate a close association between biomarkers of ferroptosis and OS and the psychiatric symptoms and cognitive deficits observed in these individuals.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"4"},"PeriodicalIF":3.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973704","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":"Impaired insight in schizophrenia is associated with higher frontoparietal cerebral blood flow: an arterial spin labeling study.","authors":"Jianmeng Song, Edgardo Carmona-Torres, Yasaman Kambari, Sofia Chavez, Fumihiko Ueno, Teruki Koizum, Aron Amaev, Ali Abdolizadeh, Vincenzo De Luca, Daniel M Blumberger, Gary Remington, Bruce Pollock, Ariel Graff-Guerrero, Philip Gerretsen","doi":"10.1038/s41537-024-00536-3","DOIUrl":"10.1038/s41537-024-00536-3","url":null,"abstract":"<p><p>Impaired insight into illness occurs in up to 98% of patients with schizophrenia, depending on the stage of illness, and leads to negative clinical outcomes. Previous neuroimaging studies suggest that impaired insight in patients with schizophrenia may be related to structural and functional anomalies in frontoparietal brain regions. To date, limited studies have investigated the association between regional cerebral blood flow (CBF) and impaired insight in schizophrenia. Therefore, we sought to investigate the relationship between regional CBF, as measured by arterial spin labeling (ASL), and impaired insight in participants with schizophrenia. A total of 32 participants were included in the analysis. Impaired insight in patients with schizophrenia was measured using the VAGUS, Self-report (VAGUS-SR). Resting-state regional CBF was measured using pseudo-continuous ASL (pCASL) and extracted using SPM12 and REX toolbox. Whole brain analysis found that impaired insight was associated with higher regional CBF in the right angular gyrus, left supramarginal gyrus, and right superior frontal region when controlling for age, gender, smoking status, and illness severity. The results indicate that impaired insight in schizophrenia is related to regional CBF in frontoparietal areas. These neuroimaging findings can serve as therapeutic targets for intervention, such as with non-invasive brain stimulation.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"2"},"PeriodicalIF":3.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967605","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":"Investigating the causal pathways among psychopathological variables, cognitive impairment, and real-life functioning in people with schizophrenia.","authors":"Luigi Giuliani, Francesco Sanmarchi, Armida Mucci, Paola Rucci, Edoardo Caporusso, Paola Bucci, Giulia M Giordano, Mario Amore, Paola Rocca, Alessandro Rossi, Alessandro Bertolino, Silvana Galderisi, Mario Maj","doi":"10.1038/s41537-024-00545-2","DOIUrl":"10.1038/s41537-024-00545-2","url":null,"abstract":"<p><p>The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"1"},"PeriodicalIF":3.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928920","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":"General medical comorbidities in psychotic disorders in the Finnish SUPER study.","authors":"Johan Ahti, Tuula Kieseppä, Willehard Haaki, Jaana Suvisaari, Solja Niemelä, Kimmo Suokas, Minna Holm, Asko Wegelius, Olli Kampman, Markku Lähteenvuo, Tiina Paunio, Jari Tiihonen, Jarmo Hietala, Erkki Isometsä","doi":"10.1038/s41537-024-00546-1","DOIUrl":"10.1038/s41537-024-00546-1","url":null,"abstract":"<p><p>Schizophrenia (SZ), schizoaffective disorder (SZA), bipolar disorder (BD), and psychotic depression (PD) are associated with premature death due to preventable general medical comorbidities (GMCs). The interaction between psychosis, risk factors, and GMCs is complex and should be elucidated. More research particularly among those with SZA or PD is warranted. We evaluated the association between registry-based psychotic disorders and GMC diagnoses in a large national sample of participants with different psychotic disorders. In addition, we examined whether body mass index (BMI) and smoking as risk factors for GMCs explain differences between diagnostic groups. This was a cross-sectional study of a clinical population of participants (n = 10,417) in the Finnish SUPER study. Registry-based diagnoses of psychotic disorders and hypertension, diabetes, chronic obstructive pulmonary disease (COPD), cancers, ischemic heart disease, and liver disorders were obtained. Participants' BMI and self-reported smoking were recorded. Total effect of diagnostic category adjusted for age and sex as well as direct effect including known risk factors was calculated using logistic regression. Regardless of diagnostic category, participants had high BMI (average 30.3 kg/m²), and current smoking was common (42.4%). Diabetes and COPD were more common in SZ than in other diagnostic categories. The differences between psychotic disorders were not explained by obesity or smoking status only. Obesity and smoking were prevalent in all diagnostic categories of psychotic disorders, and continued efforts at prevention are warranted. Additional differences in GMC prevalence exist between psychotic disorders that are not explained by obesity and smoking.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"124"},"PeriodicalIF":3.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911332","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":"White matter lipidome alterations in the schizophrenia brain.","authors":"Dmitry Senko, Olga Efimova, Maria Osetrova, Nikolay Anikanov, Maria Boyko, Maksim Sharaev, Anna Morozova, Yana Zorkina, Maksim Kislov, Georgiy Kostyuk, Elena Stekolshchikova, Philipp Khaitovich","doi":"10.1038/s41537-024-00542-5","DOIUrl":"10.1038/s41537-024-00542-5","url":null,"abstract":"<p><p>Numerous brain imaging studies have reported white matter alterations in schizophrenia, but the lipidome analysis of the corresponding tissue remains incomplete. In this study, we investigated the lipidome composition of six subcortical white matter regions corresponding to major axonal tracks in both control subjects and schizophrenia patients. All six regions exhibited a consistent pattern of quantitative lipidome alterations in schizophrenia, involving myelin-forming and mitochondria associated lipid classes. While alteration levels of myelin-forming lipids, particularly sphingolipids, aligned with the extent of the myelin changes reported in structural brain imaging studies, a significant decrease of mitochondria in the white matter, indicated by the lipidome alterations, was not previously investigated. To verify this effect, we performed lipidome analysis in a larger set of individuals and in the mitochondria-enriched membrane fraction, as well as directly quantified mitochondrial content. Our results suggest a substantial reduction of the mitochondrial quotient accompanied by the imbalance in myelin lipids in schizophrenia white matter.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"123"},"PeriodicalIF":3.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899376","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":"Response to clozapine in treatment resistant schizophrenia is related to alterations in regional cerebral blood flow.","authors":"Junyu Sun, Fernando Zelaya, Kyra-Verena Sendt, Grant McQueen, Amy L Gillespie, John Lally, Oliver D Howes, Gareth J Barker, Philip McGuire, James H MacCabe, Alice Egerton","doi":"10.1038/s41537-024-00544-3","DOIUrl":"10.1038/s41537-024-00544-3","url":null,"abstract":"<p><p>PET and SPECT studies in treatment-resistant schizophrenia (TRS) have revealed significant alterations in regional cerebral blood flow (CBF) during clozapine treatment, which may vary according to the clinical response. Here, we used the more recent MRI approach of arterial spin labelling (ASL) to evaluate regional CBF in participants with TRS (N = 36) before starting treatment with clozapine compared to in healthy volunteers (N = 16). We then compared CBF in the TRS group, before and after 12 weeks of treatment with clozapine (N = 24); and examined the relationship of those differences against changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores over the treatment period. We observed widespread reductions in CBF in TRS compared to in healthy volunteers (p < 0.05). After covarying for global CBF and age, lower CBF in frontal and parietal regions was still evident (p < 0.05, FWE corrected). Clozapine treatment was associated with longitudinal decreases in CBF in the anterior cingulate cortex (ACC) (p < 0.05). Higher striatal CBF at baseline was associated with greater improvement in total and general symptoms following clozapine, and higher hippocampal CBF was associated with greater improvement in total and positive symptoms. Longitudinal reductions in CBF in the ACC and thalamus were associated with less improvement in negative (ACC), positive (thalamus), and total (thalamus) symptoms. These findings suggest that changes in CBF on clozapine administration in TRS may accompany symptomatic improvement, and that CBF prior to clozapine initiation may determine the degree of clinical response.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"122"},"PeriodicalIF":3.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883988","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":"Effects of mindfulness-based intervention in preventing relapse in patients with remitted psychosis: a randomized controlled trial.","authors":"Christy Lai Ming Hui, Charlie Cheuk Lam Wong, Eddie Chi Yuen Lui, Tsz Ching Chiu, Tiffany Junchen Tao, Evie Wai Ting Chan, Jingxia Lin, Alan C Y Tong, Yi Nam Suen, Charles W H Chan, Wai Song Yeung, Edwin Ho Ming Lee, Sherry Kit Wa Chan, Wing Chung Chang, Eric Yu Hai Chen","doi":"10.1038/s41537-024-00539-0","DOIUrl":"10.1038/s41537-024-00539-0","url":null,"abstract":"<p><p>Stress is a key factor in psychotic relapse, and mindfulness offers stress resilience and well-being benefits. This study examined the effects of mindfulness-based intervention for psychosis (MBI-p) in preventing relapse at 1 year among patients with remitted psychosis in Hong Kong. MBI-p is a newly developed manual-based mindfulness protocol and was tested to have improved well-being and clinical outcomes in a pilot study with remitted psychosis patients. In this multisite, single-blind, 1-year randomized controlled trial (RCT), 152 fully remitted patients diagnosed with schizophrenia or non-affective psychosis were randomized to receive either a 7-week MBI-p or a 7-week psychoeducation program. Outcomes were assessed before and after the intervention, and then monthly for one year. Relapse rate and severity at one year were the primary outcomes. Secondary outcomes included psychopathology, functioning, mindfulness, and psychosocial factors such as stress and expressed emotions. No significant differences were found in the rate and severity of relapse between the MBI-p and psychoeducation groups in either intention-to-treat or per-protocol analyses. While MBI-p improved observation and non-reactivity to the inner experience of mindfulness, psychoeducation was found to benefit functioning and psychosocial functioning more than MBI-p. This is the first RCT to test MBI-p's effectiveness in preventing relapse among patients with remitted psychosis in Hong Kong. We postulate that the lack of significance is due to the heightened effectiveness of psychoeducation in coping with stress during the pandemic and the multifactorial causes leading to relapse. This suggests the possibility of combining these two interventions to improve their efficacy. Trial registration: NCT04060498.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"120"},"PeriodicalIF":3.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866713","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":"Investigation of choroid plexus variability in schizophrenia-spectrum disorders-insights from a multimodal study.","authors":"Vladislav Yakimov, Joanna Moussiopoulou, Lukas Roell, Marcel S Kallweit, Emanuel Boudriot, Matin Mortazavi, Sergi Papiol, Lenka Krčmář, Mattia Campana, Eva C Schulte, Nicolas Glaichenhaus, Emanuela Martinuzzi, Sean Halstead, Nicola Warren, Dan Siskind, Isabel Maurus, Alkomiet Hasan, Peter Falkai, Andrea Schmitt, Florian J Raabe, Daniel Keeser, Elias Wagner","doi":"10.1038/s41537-024-00543-4","DOIUrl":"10.1038/s41537-024-00543-4","url":null,"abstract":"<p><p>Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated with peripheral inflammation. However, it is unclear whether such an enlargement delineates a biologically defined subgroup of SSD. Moreover, it remains elusive how ChP is linked to brain regions associated with peripheral inflammation in SSD. A cross-sectional cohort of 132 individuals with SSD and 107 age-matched healthy controls (HC) underwent cerebral magnetic resonance imaging (MRI) and clinical phenotyping to investigate the ChP and associated regions. A case-control comparison of ChP volumes was conducted, and structural variance was analyzed by employing the variability ratio (VR). K-means clustering analysis was used to identify subgroups with distinct patterns of the ventricular system, and the clusters were compared in terms of demographic, clinical, and immunological measures. The relationship between ChP volumes and brain regions, previously associated with peripheral inflammation, was investigated. We did not find a significant enlargement of the ChP in SSD compared to HC but detected an increased VR of ChP and lateral ventricle volumes. Based on these regions, we identified 3 clusters with differences in cognitive measures and possibly inflammatory markers. Larger ChP volume was associated with higher volumes of hippocampus, putamen, and thalamus in SSD but not in HC. This study suggests that ChP variability, but not mean volume, is increased in individuals with SSD, compared to HC. Larger ChP volumes in SSD were associated with higher volumes of regions previously associated with peripheral inflammation.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"121"},"PeriodicalIF":3.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873550","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":"Variations of blood D-serine and D-aspartate homeostasis track psychosis stages.","authors":"Antonio Rampino, Martina Garofalo, Tommaso Nuzzo, Maria Favia, Silvia Saltarelli, Rita Masellis, Martina Grazia Asselti, Teresa Claudia Pennacchio, Dario Bruzzese, Francesco Errico, Matteo Vidali, Alessandro Bertolino, Alessandro Usiello","doi":"10.1038/s41537-024-00537-2","DOIUrl":"10.1038/s41537-024-00537-2","url":null,"abstract":"<p><p>Schizophrenia (SCZ) is a severe psychotic disorder characterized by a disruption in glutamatergic NMDA receptor (NMDAR)-mediated neurotransmission. Compelling evidence has revealed that NMDAR activation is not limited to L-glutamate, L-aspartate, and glycine since other free amino acids (AAs) in the atypical D-configuration, such as D-aspartate and D-serine, also modulate this class of glutamatergic receptors. Although dysregulation of AAs modulating NMDARs has been previously reported in SCZ, it remains unclear whether distinct variations of these biomolecules occur during illness progression from at-risk premorbid to clinically manifest stage. To probe this issue, we used High-Performance Liquid Chromatography (HPLC) to measure serum levels of D- and L-AAs that stimulate NMDARs across four groups of individuals diagnosed with (a) At-Risk Mental State (ARMS) for psychosis, (b) First Episode of Psychosis (FEP), (c) full-blown SCZ and (d) Healthy Donors (HD). We examined how diagnosis, demographic features, and antipsychotic treatment influence the variation of AA levels throughout psychosis progression. Finally, we explored the potential association between AA blood concentrations and clinical and cognitive measures related to psychosis. Our findings identified inter-group differences in serum AA composition, highlighting that the upregulation of D-serine/total serine and D-aspartate/total aspartate ratios represent a peculiar blood biochemical signature of early stages of psychosis progression, while increased L-glutamate, L-aspartate and glycine associate with chronic SCZ diagnosis. The present findings provide direct evidence for early dysregulation of D-AA metabolism and have potential implications for the identification of biomarkers for the early detection and staging of psychosis.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"115"},"PeriodicalIF":3.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866302","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 neurodevelopmental regulatory role and clinical value of hsa-circ-CORO1C-hsa-miR-708-3p-JARID2 + LNPEP axis in early-onset schizophrenia.","authors":"Zexuan Li, Xinzhe Du, Xijin Wang, Jianzhen Hu, Meiqi Liu, Yao Gao, Zhifen Liu, Xiaohua Cao, Xinrong Li, Yong Xu, Sha Liu","doi":"10.1038/s41537-024-00538-1","DOIUrl":"10.1038/s41537-024-00538-1","url":null,"abstract":"<p><p>Genes discovered by previous epigenetic studies of schizophrenia have focused solely on diagnostics or pathology, potentially leading to a disconnection between them. Using these molecules to identify the disease is considered insufficient. MicroRNAs (miRNAs) binding to messenger RNAs (mRNAs) can lead to mRNA degradation, while circular RNAs (circRNAs), by binding to miRNAs as sponge, can reduce the inhibitory effect of miRNAs on mRNAs. CircRNAs, miRNAs, and mRNAs form the multi-molecular axis that can bind and regulate expression between each other, thereby affecting biological function. This study focused on early-onset schizophrenia (EOS), aiming to identify the multi-molecular axis consisting of circRNAs, miRNAs, and mRNAs with both neurobiological function and diagnostic value to assist in disease identification. In the discovery cohort of 10 drug-naïve, first-episode patients with EOS and 10 matched healthy controls (HCs), differentially expressed (DE) circRNAs and miRNAs were identified via Illumina high-throughput sequencing. In the validation cohort-1 (40 EOS v.s. 50 HCs), the candidate circRNAs and miRNAs were further screened using Real-time polymerase chain reaction, Sanger sequencing, and RNase R assay. Combining dual-luciferase reporter assay with overexpression/knockdown experiments, the axis consisting of circRNAs-miRNAs-mRNAs with binding and regulatory relationships has been established. Subsequently, the functions of genes on the axis were explored through zebrafish embryo manipulation and neural differentiation. The clinical value of the entire axis was assessed in the validation cohort-2 (84 EOS v.s. 67 HCs). Patients with EOS exhibited expression profiles of 487 DE circRNAs and 101 DE miRNAs compared to HCs. The binding relationships and regulatory effects of hsa-circ-CORO1C on hsa-miR-708-3p, hsa-miR-708-3p on target JARID2 and LNPEP were elucidated. Among them, hsa-miR-708-3p caused aberrant phenotypes including significant craniocerebral malformation and impaired neuron axon growth. JARID2 and LNPEP could facilitate neuronal differentiation and augment synaptic formation. In addition to their neurobiological functions, the combined diagnostic efficacy of the whole axis, where hsa-circ-CORO1C could serve as a sponge for hsa-miR-708-3p to alleviate its suppressive effects on JARID2 and LNPEP, surpassed any individual gene we found in EOS. Our study demonstrated a multi-molecular axis, hsa-circ-CORO1C-hsa-miR-708-3p-JARID2 + LNPEP, in EOS for the first time. By integrating evidence from genetic, neurophenotypic, and clinical perspectives, we have expanded the comprehension of the pathological mechanism and provided the reference for identifying reliable objective diagnostic biomarkers for EOS.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"10 1","pages":"119"},"PeriodicalIF":3.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866279","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}