Schizophrenia Research最新文献

{"title":"Issue Highlights","authors":"","doi":"10.1016/S0920-9964(25)00314-7","DOIUrl":"10.1016/S0920-9964(25)00314-7","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"283 ","pages":"Page A1"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microstructural alterations of the corpus callosum in affective and non-affective early psychosis: A diffusion magnetic resonance imaging study","authors":"Hossein Sanjari Moghaddam ,&nbsp;Mohammad Hadi Aarabi ,&nbsp;Iman Kiani ,&nbsp;Giulia Cattarinussi ,&nbsp;Shiva Khodadadi ,&nbsp;Sahar Delavari ,&nbsp;Fabio Sambataro","doi":"10.1016/j.schres.2025.08.010","DOIUrl":"10.1016/j.schres.2025.08.010","url":null,"abstract":"<div><h3>Background</h3><div>Early psychosis (EP) is associated with a disrupted integrity of the white matter microstructure of a variety of brain regions, especially the corpus callosum (CC). In this study, we used diffusion-weighted magnetic resonance imaging data of patients with EP and employed diffusion tensor imaging (DTI), free water-corrected diffusion, and neurite orientation dispersion and density imaging (NODDI) to comprehensively assess the white matter microstructure.</div></div><div><h3>Methods</h3><div>106 patients with EP (84 non-affective and 22 affective) and 51 healthy controls (HCs) were included from the Human Connectome Project in the Early Psychosis dataset. We used tract-specific analysis for tractography of three parts of the CC and quantified the diffusion measurements for each segment. CC measurement differences between EP vs. HCs and affective vs. non-affective psychosis were assessed by multivariate analysis of covariance. Principal component analysis was used for dimension reduction of diffusion metrics.</div></div><div><h3>Results</h3><div>EP was associated with disrupted white matter integrity in the body of CC indicated by a lower fractional anisotropy and intracellular volume fraction, alongside increased diffusivity measures. None of the CC subregions showed a significant difference in the genu and splenium of the CC between EP and HC groups or between affective and non-affective subgroups. Furthermore, lower white matter integrity in the genu was marginally associated with increased symptom severity.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that microstructural alterations of white matter fibers crossing CC may underlie the pathophysiology of EP. These findings may contribute to a growing body of evidence pointing to white matter disruption as a potential biomarker of disease vulnerability.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 237-247"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethnic bias in risk assessment of patients with early-onset first episode psychosis","authors":"Lauren Nashashibi ,&nbsp;Daniel Harlev ,&nbsp;Shulamit Grinapol ,&nbsp;Tomer Karny ,&nbsp;Itai Horowitz ,&nbsp;Haya Wachtel ,&nbsp;Eyal Bergmann","doi":"10.1016/j.schres.2025.08.015","DOIUrl":"10.1016/j.schres.2025.08.015","url":null,"abstract":"<div><h3>Background</h3><div>First episode psychosis (FEP) constitutes a common psychiatric emergency. A key decision in the management of FEP involves risk assessment, which directly influences the need for involuntary hospitalization. However, the impact of demographic variables of patients and psychiatrists on FEP risk assessment remains incompletely characterized. We sought to test whether the ethnicity of patients and psychiatrists influences the risk assessment of FEP.</div></div><div><h3>Design</h3><div>A retrospective cohort study examined emergency department visits from 2014 to 2023 at Rambam Health Care Campus involving adults aged 18 to 40 with FEP. A generalized linear mixed model assessed whether patient and psychiatrist demographics affected risk assessment outcomes.</div></div><div><h3>Results</h3><div>A total of 625 FEP cases were examined (mean age of 26.24 years, SD = 5.69, 66.88 % men, 67.52 % Jewish). The analysis included 27 psychiatrists (55.56 % women; 66.67 % Jewish). An unadjusted comparison revealed a higher proportion of immediate risk among Arab patients compared to Jewish patients (59.11 % vs. 49.52 %, <em>P</em> = 0.025). Further regression analysis revealed a significant interaction between patient and psychiatrist ethnicity (OR = 0.38, <em>P</em> = 0.013), suggesting that the higher proportion of cases with positive immediate risk assessments among Arabs was attributable to Jewish psychiatrists, who were more likely to classify them as being at immediate risk.</div></div><div><h3>Conclusions</h3><div>The results suggest that what appears to be an ethnic difference in the proportions of cases with immediate risk may reflect a bias among Jewish psychiatrists in evaluating Arab patients. This emphasizes the complexities of assessing minority groups and highlights the need for culturally sensitive psychiatric care.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 231-236"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cells are associated with negative symptoms in persons with anti-gliadin antibody positive schizophrenia and related disorders","authors":"Deepak Salem ,&nbsp;Sarah M. Clark ,&nbsp;Daniel J.O. Roche ,&nbsp;Nevil J. Singh ,&nbsp;Monica V. Talor ,&nbsp;Robert W. Buchanan ,&nbsp;Valerie Harrington ,&nbsp;Zhenyao Ye ,&nbsp;Shuo Chen ,&nbsp;Deanna L. Kelly","doi":"10.1016/j.schres.2025.08.008","DOIUrl":"10.1016/j.schres.2025.08.008","url":null,"abstract":"<div><h3>Background</h3><div>About one-third of persons with schizophrenia and related disorders (SRD) have elevated anti-gliadin IgG antibodies (AGA), associated with gluten sensitivity, increased negative symptoms, greater functional impairments, and limited therapeutic options. Alterations in T cells have been demonstrated in SRD, and we have previously shown that regulatory T cells (Tregs) are increased and correlate with fewer negative symptoms in SRD.</div></div><div><h3>Methods</h3><div>We investigated the relationship of T cells and negative symptoms in 26 clinically stable, medicated persons with AGA positive (AGA+) or AGA negative (AGA-) SRD. Negative symptoms were evaluated using the Scale for the Assessment of Negative Symptoms (SANS). Blood samples were analyzed for: 1) AGA-IgG levels (measured by ELISA; AGA positivity defined as ≥20U), 2) flow cytometry to quantify proportions of pan-T cells (CD3⁺), helper T cells (CD3⁺CD4⁺), Tregs (CD3⁺CD4⁺CD25⁺Foxp3⁺), and activated Tregs (aTregs) (CD3⁺CD4⁺CD25⁺Foxp3⁺CD45RA⁻) and 3) multiplex analysis of circulating immune markers.</div></div><div><h3>Results</h3><div>46 % of SRD participants were AGA+ and in this group, aTregs were increased in proportion (p = 0.0061). In AGA+ SRD, pan-T cells were correlated with higher SANS total, anhedonia, avolition and alogia scores (all p &lt; 0.05), while increased helper T cells and Tregs were correlated with less negative symptoms (respectively, SANS total, blunting, anhedonia, and alogia; SANS total, anhedonia, alogia; all p &lt; 0.05). AGA+ SRD also had several elevated immune markers, corresponding with a pro-inflammatory phenotype.</div></div><div><h3>Conclusions</h3><div>These hypothesis-generating findings suggest T cell dysfunction in AGA+ SRD, suggesting Tregs mitigating negative symptom severity, but also an unidentified other T cell population possibly contributing to negative symptomatology.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 222-230"},"PeriodicalIF":3.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the abnormal neural variability in schizophrenia: A TMS-EEG study","authors":"Zikang Niu ,&nbsp;Lina Jia ,&nbsp;Lu Tian ,&nbsp;Yi Liu ,&nbsp;Siyuan Lian ,&nbsp;Liu Yang ,&nbsp;Yang Li ,&nbsp;Xiaoli Li","doi":"10.1016/j.schres.2025.08.005","DOIUrl":"10.1016/j.schres.2025.08.005","url":null,"abstract":"<div><h3>Background</h3><div>The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) (TMS-EEG) has become a pivotal tool for investigating neurophysiological mechanisms in schizophrenia (SZ), a disorder marked by pronounced clinical and neurobiological heterogeneity. However, conventional analyses of TMS-EEG data frequently neglect trial-to-trial neural variability, a critical dimension of dynamic brain responses that may reflect core pathophysiological features of SZ.</div></div><div><h3>Methods</h3><div>The TMS-EEG data and MCCB were collected from 45 SZ patients and 45 healthy controls (HC). Trial-by-trial variability (TTV) was quantified through the maximum eigenvalue extracted from singular value decomposition of TMS-evoked trials data. Correlation analyses were conducted between TTV and scores.</div></div><div><h3>Results</h3><div>TMS pulse significantly reduced the TTV of neural activity in both groups. Compared to HC, SZ patients demonstrated increased beta TTV but decreased theta TTV. Notably, elevated beta TTV correlated with reasoning and problem solving, working memory and verbal learning while diminished theta TTV was associated with speed of processing and social cognition.</div></div><div><h3>Conclusions</h3><div>This pioneering study establishes altered trial-wise neural variability as a novel electrophysiological signature of SZ. The frequency-specific TTV abnormalities and their cognitive correlations suggest that dysregulated neural dynamics may underlie core symptomatology, providing quantifiable biomarkers for clinical stratification and therapeutic development.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 214-221"},"PeriodicalIF":3.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A two-year longitudinal investigation of insula subregional cortical thickness and surface area in early psychosis","authors":"Andrew R. Kittleson ,&nbsp;Neil D. Woodward ,&nbsp;Maureen McHugo ,&nbsp;Jinyuan Liu ,&nbsp;Simon N. Vandekar ,&nbsp;Kristan Armstrong ,&nbsp;Baxter Rogers ,&nbsp;Stephan Heckers ,&nbsp;Julia M. Sheffield","doi":"10.1016/j.schres.2025.08.007","DOIUrl":"10.1016/j.schres.2025.08.007","url":null,"abstract":"<div><h3>Background</h3><div>Smaller insula volume is consistently observed in psychotic disorders; however, alterations in associated cortical features—thickness and surface area—are less clear. We examined insula thickness and surface area changes in early psychosis to determine whether alterations were a) present in the early stages of psychosis, b) specific to any of the insula's three cytoarchitectural subregions (agranular, dysgranular, and granular) and c) related to behaviors impacted in psychosis.</div></div><div><h3>Methods</h3><div>63 non-affective early psychosis (EP) and 59 healthy comparison (HC) participants completed 2–4 study visits over two years. Cortical thickness and surface area was quantified via T1 MRI and segmented into three anatomic subregions: anterior (agranular), middle (dysgranular), and posterior (granular). Perceptual aberrations, cognition, and psychotic symptoms were measured; group differences and longitudinal changes were tested using linear mixed models.</div></div><div><h3>Results</h3><div>EP participants had lower cortical thickness in all insula subregions and thickness declined at a normative rate, compared to HC participants. Insula surface area, on the other hand, was intact in EP and also showed a normative pattern of decline over two years. No significant associations were observed between structural metrics and clinical phenotypes.</div></div><div><h3>Conclusions</h3><div>In early psychosis, insula cortical thickness, but not surface area, is disrupted, and demonstrates normative changes over two years. This pattern is observed for all insula subregions. These data suggest that cortical thickness of the insula is structurally impacted in schizophrenia-spectrum disorders and may be the result of abnormal neurodevelopment occurring prior to illness onset.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 204-213"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquaporin-4 positive extracellular vesicles and cytokines in cerebrospinal fluid in schizophrenia and obsessive-compulsive disorder, and associations with peripheral cytokines","authors":"Mats B. Humble ,&nbsp;Fariborz Mobarrez ,&nbsp;Daniel Eklund ,&nbsp;Susanne Bejerot ,&nbsp;Lennart Wetterberg","doi":"10.1016/j.schres.2025.08.006","DOIUrl":"10.1016/j.schres.2025.08.006","url":null,"abstract":"<div><div>Schizophrenia and obsessive-compulsive disorder (OCD) are complex neuropsychiatric disorders with emerging evidence implicating immune and neuroinflammatory mechanisms. This exploratory pilot study investigated aquaporin-4 positive (AQP4+) extracellular vesicles (EVs) in the cerebrospinal fluid (CSF) of 11 treatment-resistant patients with schizophrenia (<em>n</em> = 5) or obsessive-compulsive disorder (OCD, <em>n</em> = 6) receiving an add-on, single-infusion rituximab (1000 mg) treatment, a B-cell depleting therapy. CSF samples were collected pre-treatment and, for a subset, again five months post-treatment. AQP4+ EV levels in CSF were quantified using flow cytometry with antibodies targeting different regions of the AQP4 molecule. We also measured selected cytokines in CSF and plasma and cytokine gene expression in peripheral blood cells.</div><div>Patients with schizophrenia exhibited higher AQP4+ EV levels compared to those with OCD. In schizophrenia, AQP4+ EVs correlated positively with the inflammatory marker CXCL8/IL-8 but negatively with CSF-TNF-α. Plasma markers CXCL8/IL-8 and TGF-β₁ were positively associated with CSF-AQP4+ EVs in schizophrenia. Between 24- and 40-times higher concentrations of CXCL8/IL-8 in CSF than in plasma suggest intrathecal production of this chemokine in both disorders. Post-treatment, AQP4+ EV levels decreased in the patients who improved following rituximab but remained stable in non-responders.</div><div>These findings suggest that astrocyte-derived extracellular vesicles may play a role in neuroinflammatory processes linked to schizophrenia and possibly also to severe OCD. The observed relationships between AQP4+ EVs and cytokines support the hypothesis that astrocyte-derived EVs could modulate intrathecal immune responses and potentially also interact with peripheral immune mechanisms. Larger studies are warranted to validate these preliminary findings.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 195-203"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining targets for urban remediation in early psychosis","authors":"Lilith Abrahamyan Empson ,&nbsp;Philippe Golay ,&nbsp;Philipp S. Baumann ,&nbsp;Jérôme Favrod ,&nbsp;Dag Söderström ,&nbsp;Zoé Codeluppi ,&nbsp;Philippe Conus","doi":"10.1016/j.schres.2025.07.028","DOIUrl":"10.1016/j.schres.2025.07.028","url":null,"abstract":"<div><h3>Aims</h3><div>The emergence of psychosis generates <em>city avoidance</em>—a drastic decrease in city attendance and a lack of capacity to benefit from city's restorative resources among early psychosis patients (EP). Patients with low and moderate city attendance (self-reported duration and frequency of city outings before and after first episode of psychosis) have reduced access to important city resources and may benefit from a city-specific recovery-oriented program. This paper aims to refine the targets for such an intervention aimed at reducing city avoidance.</div></div><div><h3>Methods</h3><div>Sociodemographic characteristics, urban practices, and psychological reactions in the city of 117 EP patients were collected via a tailor-made questionnaire. Survey-based data and medical record-based data were compared through Bayesian modelling based on the degree of city attendance.</div></div><div><h3>Results</h3><div>19 % of EP patients reported low city attendance (&lt;1 h/day), 47.4 % reported moderate city attendance (1–4 h/day) and 33.6 % reported high city attendance (&gt;4 h/day). Variables discriminating between patients with low, moderate, and high city attendance were sex, low level of premorbid adjustment, low level of functioning at the end of the treatment phase, global negative perception of the city, higher levels of anxiety and persecutory feelings, and elements related to social defeat.</div></div><div><h3>Conclusions</h3><div>A significant proportion of EP patients avoids the city and has potentially restricted access to city resources. We identified various patients' and environment characteristics of interest when designing a strategy aimed at reducing city avoidance and promoting a better integration in the community for early psychosis patients.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 186-194"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychosis in Huntington's disease: a review and comparison with schizophrenia","authors":"James B. Badenoch ,&nbsp;Hugh Rickards ,&nbsp;Robert A. McCutcheon ,&nbsp;Akshay Nair","doi":"10.1016/j.schres.2025.07.012","DOIUrl":"10.1016/j.schres.2025.07.012","url":null,"abstract":"<div><div>Psychosis is a relatively rare phenomenon in Huntington's disease (HD) yet it occurs more commonly amongst individuals with HD than in the general population. Its presence is associated with significant distress and caregiver burden. This review evaluates the epidemiology, aetiology, phenomenology, neurobiology and treatment of psychosis in HD, drawing comparisons with schizophrenia as an archetypal psychotic disorder. We conducted a detailed literature search and narrative synthesis and found that prevalence estimates of psychosis in HD varied widely (4.1–17.6 %). While generally more common in those with established motor symptoms, psychosis occurred throughout the HD course. Its presence conferred a poorer prognosis, including greater functional and cognitive decline. No distinct phenomenology of psychosis in HD emerged; paranoid ideation was common whereas formal thought disorder was rarely reported. Like schizophrenia, psychosis in HD is associated with depression, suicidality, apathy, executive and social cognitive dysfunction. The neurobiology of psychosis in HD is not well understood however HD neurobiology shares some overlap with schizophrenia. Despite the absence of mesostriatal hyperdopaminergic transmission, frontostriatal network dysfunction, glutamatergic dysregulation and medium spiny neuron pathology could contribute to psychosis manifestation. The development of psychosis in HD is conceptualised within a stress-diathesis framework, involving an interaction between genetic risk (with some shared vulnerability to schizophrenia), neuronal changes and psychosocial stressors. Clinically, this implies a rationale for utilising therapeutic approaches trialled in schizophrenia, as there is no evidence that psychosis in HD requires fundamentally different treatment, except for an awareness of the antipsychotic effects on HD motor symptoms.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"284 ","pages":"Pages 175-185"},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Young first-episode psychosis patients exhibit impaired microvascular function in the skin and low systemic nitric oxide availability, independent of classical cardiovascular risk factors","authors":"Joanna Suraj-Prażmowska ,&nbsp;Brygida Marczyk ,&nbsp;Natalia Śmierciak ,&nbsp;Marta Szwajca ,&nbsp;Anna Kurpińska ,&nbsp;Agnieszka Kij ,&nbsp;Marzena Frołow ,&nbsp;Veronika Aleksandrovych ,&nbsp;Maciej Pilecki ,&nbsp;Stefan Chlopicki","doi":"10.1016/j.schres.2025.07.002","DOIUrl":"10.1016/j.schres.2025.07.002","url":null,"abstract":"<div><div>Impaired endothelial function in patients with psychotic disorders may contribute to increased cardiovascular mortality, but the mechanisms involved remain unclear.</div><div>Here, we comprehensively analyzed endothelial function in 33 young (median age 18: IQR 17–27) patients diagnosed with first-episode psychosis (FEP), examining large vessels (flow-mediated dilation; FMD) and the microcirculation in peripheral vessels (peripheral arterial tonometry following reactive hyperemia; RH-PAT) and in the skin (flow-mediated skin fluorescence; FMSF). We also measured the plasma concentration of nitric oxide (NO) metabolites (nitrite/nitrate) and 18 biomarkers related to endothelial function, including those representative of glycocalyx damage (SDC-1), endothelial inflammation (sVCAM-1), disrupted endothelial permeability (Angpt-1, Angpt-2), and hemostasis (TAFI, THBS-1).</div><div>In FEP patients, FMD and RH-PAT remained largely unchanged, but skin microcirculation measured by FMSF was impaired, with pronounced alterations in baseline microvascular oscillations and reactive hyperemic response. Plasma nitrite concentration in FEP patients was significantly lowered, but the profile of biomarkers did not display typical pattern of pro-inflammatory and pro-thrombotic changes associated with endothelial dysfunction, but prominent lowering of adrenomedullin and annexin A5 levels. FEP patients had higher white blood cell counts, total cholesterol, and triglycerides levels, but these parameters did not correlate with any of the vascular readouts.</div><div>In conclusion, young FEP patients displayed a distinct endotype of endothelial dysfunction with impaired systemic NO bioavailability and prominent functional alterations in the microcirculation of the skin. These results indicate that the assessment of functional changes in skin microcirculation by FMSF may provide novel insights into the early negative effects of psychosis on the microvasculature.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"283 ","pages":"Pages 188-199"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}