Schizophrenia (Heidelberg, Germany)最新文献

{"title":"Aberrant salience is selectively associated with ventral midbrain connectivity to the dorsal but not ventral striatum.","authors":"Yinan Li, Naoya Oishi, Qi Dai, Yukako Nakagami, Lichang Yao, Takahiko Kawashima, Yujiro Yoshihara, Manabu Kubota, Yuko Nakamura, Shinsuke Koike, Toshiya Murai, Jun Miyata","doi":"10.1038/s41537-026-00795-2","DOIUrl":"10.1038/s41537-026-00795-2","url":null,"abstract":"<p><p>The dorsal midbrain-striatal dopaminergic stream encodes salience in animals, while it's unknown in humans. The midbrain-striatal dopaminergic hyperactivity is postulated to attribute aberrantly-heightened salience to ordinary stimuli, forming delusion and hallucination. While animal studies implicate the ventral midbrain-striatal stream, patient studies suggest the dorsal stream, leaving the precise localization of aberrant salience unclear. We investigated these issues by examining midbrain-striatal functional connectivity. Resting-state functional MRI was acquired from 116 patients with schizophrenia (SCZ) and 224 age- and sex-matched healthy controls (HC). Subjective aberrant salience was assessed using the Aberrant Salience Inventory (ASI). Functional connectivity was computed between six striatal seeds (bilateral ventral limbic, dorsal executive, and dorsal sensorimotor striata) and the dopaminergic midbrain voxels (ventral tegmental area and substantia nigra). We tested (1) the presence of a ventral-to-dorsal connectivity gradient along anterior-to-posterior and inferior-to-superior axes; (2) the main effects of diagnosis and ASI and their interaction on connectivity; and (3) their associations with psychotic symptoms. Both anterior-to-posterior and inferior-to-superior connectivity gradients were confirmed. A significant main effect of diagnosis was observed in connectivity between the left anterior midbrain and ventral limbic striatum, which was reduced in SCZ than in HC. A significant diagnosis-by-ASI sensory subscale interaction was found for connectivity between the left anteroinferior midbrain and the dorsal sensorimotor striatum. This ASI subscale was significantly correlated with positive symptoms (all P < 0.05 family-wise error fully corrected). These findings demonstrate the ventral-to-dorsal midbrain-striatal gradients in humans and indicate a more complex localization of aberrant salience than previously assumed.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042623","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":"Revisiting symptom dimensions in schizophrenia with exploratory graph analysis.","authors":"Susan Illing, Stefan Leucht","doi":"10.1038/s41537-026-00799-y","DOIUrl":"10.1038/s41537-026-00799-y","url":null,"abstract":"<p><p>The Positive and Negative Syndrome Scale (PANSS) groups symptoms into three categories, but factor analyses suggest five dimensions with superior psychometric properties. Exploratory graph analysis (EGA) offers a novel network-based approach that provides additional information such as connection of domains, bridge symptoms, and centrality measures. We applied EGA to PANSS data from 1213 participants with schizophrenia at baseline and after six weeks of treatment. We identified symptom clusters with community detection algorithms, item stability with bootstrapping, and the connecting role of individual items with bridge centrality metrics. EGA consistently revealed five communities: positive symptoms, negative symptoms, cognitive disorganization, depression/anxiety, and hostility/excitement. The latter was less stable and its symptom P6 (suspiciousness) moved to the positive symptom domain at endpoint. Other item assignments were stable, except for items P5 (grandiosity), and G8 (uncooperativeness). P4 (excitement), P6, G8, and G15 (preoccupation) emerged as key bridge symptoms. Overall, the replication of five factors with a different method underlines their clinical importance.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908336","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 neurobiological correlates of tardive dyskinesia in schizophrenia spectrum disorders and mood disorders.","authors":"Dilsa Cemre Akkoc Altinok, Sebastian Volkmer, Stefan Fritze, Geva A Brandt, Lana Wölfl, Jacqueline Kukovic, Amanda Bellanti, Anastasia Pavlidou, Sofie von Känel, Stephanie Lefebvre, Andreas Meyer-Lindenberg, Sebastian Walther, Dusan Hirjak","doi":"10.1038/s41537-026-00796-1","DOIUrl":"10.1038/s41537-026-00796-1","url":null,"abstract":"<p><p>Tardive dyskinesia (TD) is a persistent sensorimotor syndrome associated with antipsychotic exposure in schizophrenia spectrum disorders (SSD) and mood disorders (MOD), yet its neurobiological basis remains poorly understood. We investigated whether TD represents a distinct clinical and neurobiological phenotype across SSD and MOD. In this study, we examined a bicentric cohort of 453 individuals with SSD (n = 360) or MOD (n = 93), including early-psychosis (EP) and multiple-episode SSD patients. TD status was defined using Schooler and Kane criteria based on the Abnormal Involuntary Movement Scale (AIMS). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Structural MRI data were processed using FreeSurfer (v7.4.1). Propensity score matching was applied to compare TD-positive and TD-negative patients while controlling for age, sex, illness duration, antipsychotic dose, and PANSS scores. TD prevalence was 10.6% in multiple-episode SSD (n = 31) and 7.5% in MOD (n = 7), whereas no EP patients met criteria for TD. Logistic regression identified male sex (p = 0.005) and higher PANSS general psychopathology scores (p = 0.021) as independent predictors of TD. TD-positive patients showed reduced paracentral cortical surface area in both the matched SSD sample (n = 86; p = 0.006, corr.) and the combined transdiagnostic sample (n = 179; p = 0.024, corr.). These alterations were absent in EP patients. In conclusion, our findings suggest that TD is a transdiagnostic phenomenon, occurring in both SSD and MOD. However, TD in SSD appears to be associated with a distinct clinical and neurobiological phenotype, marked by greater illness severity, male predominance, and focal sensorimotor cortical alterations.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815197","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":"Schizophrenia: temporal imprecision in phase, time, and frequency domains.","authors":"Saeid Kholghi, Georg Northoff","doi":"10.1038/s41537-026-00792-5","DOIUrl":"10.1038/s41537-026-00792-5","url":null,"abstract":"<p><p>Schizophrenia is associated with deficits in input processing, but the underlying neural dynamics of this deficit remain unclear. A recent model proposes temporal imprecision as a basic disturbance driving the input processing deficit. To address the question of whether temporal imprecision affects all three domains of the brain's signal (e.g., phase, time, and frequency) as early as first episode schizophrenia, we analyzed magnetoencephalography (MEG) data from 25 first-episode schizophrenia (FESZ) participants and 24 healthy controls (HC) during a passive auditory oddball task with standard, pitch deviant, and duration deviant tones while watching a silent movie. We quantified temporal precision via (i) intertrial phase coherence (ITPC), (ii) intrinsic neural timescale (INT), and (iii) power spectral density (PSD) heterogeneity. For all three signal domains, we also calculated their temporal variability in sliding windows over the MEG recording. FESZ showed reduced intertrial phase coherence to both deviant tones, with a broader time and frequency range for the duration deviant ITPC reduction. Intrinsic neural timescales were prolonged in FESZ subjects. PSD profiles were more heterogeneous and broader during the auditory task in the FESZ group. FESZ subjects also showed increased temporal variability in all three signal domains across sliding windows. Finally, significant associations were observed between temporal variability in all three signal domains, including their association to impaired duration deviant mismatch negativity amplitude in first episode schizophrenia, whereas these associations were largely absent for healthy participants. We conclude that first-episode schizophrenia shows convergent temporal imprecision at specific time points as well as between time points in all three signal domains including phase, time, and frequency; this is consistent with temporal imprecision as a domain-general basic disturbance of input processing in schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066202","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":"Reduced amplitude of low frequency fluctuation in the sensorimotor cortex in early psychosis: association with motor dexterity and hyperconnectivity.","authors":"Jason Smucny, Korey P Wylie, Jason R Tregellas, Stephanie M Hare","doi":"10.1038/s41537-026-00789-0","DOIUrl":"10.1038/s41537-026-00789-0","url":null,"abstract":"<p><p>Previous studies have demonstrated widespread regional abnormalities in blood oxygen level-dependent (BOLD) amplitude of low frequency fluctuation (ALFF) in psychotic disorders. How regional ALFF is related to functional connectivity and behavior in psychotic illness, however, is poorly understood. Here we examined voxelwise ALFF across the brains of subjects with early psychosis (EP) vs. healthy controls (HCs) as well as its relationships to functional connectivity and task performance. Resting state fMRI data from 55 HCs and 109 participants with EP from the Human Connectome Project-Early Psychosis were analyzed. Our analytic strategy was to examine ALFF across the whole brain to determine what regions showed significant differences in the psychosis group and then determine how those regional abnormalities in ALFF were related to connectivity patterns with other brain areas. We then examined correlations between these measures and performance on task-relevant to the observed circuitry. Significantly lower ALFF was observed in the sensorimotor cortex in participants with EP vs. HC. Decreased sensorimotor ALFF in EP, furthermore, was associated with poor motor dexterity and cognitive function. Finally, in participants with EP, ALFF showed increased connectivity with the cerebellum, anterior cingulate, and insula. Our results suggest that spontaneous low-frequency blood oxygen level-dependent fluctuation amplitude is significantly lower in sensorimotor cortex in EP, and that this change is associated with poor motor skills and cognition. Hyperconnectivity within the observed circuits in participants with EP may indicate more widespread pathology with areas that show abnormally low levels of baseline BOLD fluctuation.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042598","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":"Using smartphone-based assessment of social experience to predict relapse in first-episode psychosis.","authors":"Ryan Hammoud, Anna Georgiades, Maria Chiara Del Piccolo, Shangqing Liu, Aljawharah Almuqrin, Robert Stewart, Ioannis Bakolis, Natasha Vorontsova, Stefania Tognin, Andrea Mechelli","doi":"10.1038/s41537-026-00786-3","DOIUrl":"10.1038/s41537-026-00786-3","url":null,"abstract":"<p><p>Social-affective changes are early indicators of psychosis relapse, yet their dynamic and subjective nature makes them difficult to capture between routine clinical assessments. Smartphone-based ecological assessments offer a method for capturing real-time social experiences in daily life. To address this gap, we examined whether social contact and social experience, measured through smartphone-based assessments, were associated with relapse following a First Episode of Psychosis (FEP), and evaluated whether smartphone data could predict relapse using machine learning. This longitudinal study included 256 individuals with FEP who completed at least one smartphone assessment, recruited from 10 Early Intervention Services across England and Wales between 2020-2023. Participants completed baseline clinical assessments and up to 30 days of daily smartphone surveys assessing social contact (alone vs with others) and social experience (a composite measure of emotional response to social contact). Relapse was assessed via structured interviews and electronic health records at 4, 8, and 12 months. Of 256 participants analysed (mean age 25.7 years [SD 5.3], 44.5% female), 8.2%, 13.5%, and 20.1% relapsed within 4, 8, and 12 months. Higher social experience consistently predicted reduced relapse risk across follow-ups, with similar effects for daily and momentary measures, while social contact showed inconsistent associations. Machine learning models using five smartphone assessments within 30 days achieved a validation accuracy of 0.790 (AUC 0.829) for predicting 12-month relapse, while data from a single smartphone assessment within 7 days achieved an accuracy of 0.715. These findings suggest that brief smartphone-based self-reports of social experience provide a low-burden, scalable tool for detecting early relapse risk and supporting more timely, personalised interventions in psychosis care.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474705","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":"Disrupted cerebellar interactions in the cerebellar-thalamo-cortical triple network model across risk states and first-episode psychosis.","authors":"Minji Ha, Inkyung Park, Hyungyou Park, Taekwan Kim, Wu Jeong Hwang, Jiseon Jang, Minah Kim, Jun Soo Kwon","doi":"10.1038/s41537-026-00783-6","DOIUrl":"https://doi.org/10.1038/s41537-026-00783-6","url":null,"abstract":"<p><p>Cerebellar dysconnectivity has been repeatedly linked to psychosis and is often accompanied by disruptions in thalamic and cortical regions. These disturbances are broadly consistent with the triple network model, which conceptualizes psychopathology as arising from abnormal interactions among the salience (SAL), default mode (DMN), and executive control (ECN) networks. However, how the cerebellum interacts with thalamic and cortical components of these networks across different psychosis risk stages and early psychosis remains unclear. Resting-state functional MRI from 37 first-episode psychosis (FEP) patients, 63 clinical high-risk (CHR) individuals, 41 unaffected relatives (URs) of schizophrenia patients, and 100 healthy controls (HCs) were analyzed. The cerebellum and thalamus were parcellated according to their functional connectivity with cortical functional networks, and the DMN, SAL, and ECN subdivisions across all three regions were used to estimate cerebellar-cortical and cerebellar-thalamic connectivity across groups. Compared with HCs, FEP patients showed widespread increases in cerebellar-cortical connectivity across all three networks, together with reduced cerebellar-thalamic connectivity, most prominently within SAL-related circuits. CHR individuals exhibited predominantly increased connectivity, with localized disruptions across cerebellar, thalamic, and cortical regions. URs did not show significant connectivity differences relative to HCs. By extending the triple network framework to include cortico-thalamo-cerebellar pathways, this study characterized how cerebellar network connectivity differs across familial risk, CHR, and FEP groups. The observed pattern suggests that early changes in CTC circuits correspond to disruptions described within the triple network model, and highlights the potential relevance of cerebellar and thalamic involvement when characterizing network alterations across the psychosis spectrum.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discriminative validity of Clinical High-Risk Status for Psychosis among help-seekers: a systematic review and meta-analysis.","authors":"Andrea Raballo, Antonio Preti, Michele Poletti","doi":"10.1038/s41537-026-00785-4","DOIUrl":"https://doi.org/10.1038/s41537-026-00785-4","url":null,"abstract":"<p><p>The Clinical High-Risk for Psychosis (CHR-P) paradigm underpins early detection strategies and informs the DSM-5 construct of Attenuated Psychosis Syndrome (APS), yet its discriminative predictive validity relative to CHR-P-negative help-seekers has not been systematically quantified. We conducted a systematic review and meta-analysis of longitudinal studies comparing transition to psychosis among help-seeking individuals according to CHR-P status. PubMed/MEDLINE and the Cochrane Library were searched from inception to June 22, 2026. Eligible studies included help-seeking samples assessed with validated CHR-P instruments and reporting psychosis transition outcomes separately for CHR-P-positive and CHR-P-negative participants. Random-effects meta-analyses estimated transition prevalence and relative risks (RRs), while heterogeneity, publication bias, and moderators were examined. 14 studies including 4477 participants (2220 CHR-P-positive and 2257 CHR-P-negative) met inclusion criteria. Estimated transition rates were 14.7% [95% CI, 9.7-21.7%) among CHR-P-positive individuals and 1.6% (95% CI, 0.8-3.2%) among CHR-P-negative individuals. CHR-P status was associated with an almost ten-fold increased risk of transition to psychosis (RR, 9.8; 95% CI, 4.5-21.82), with no significant moderation by follow-up duration or sample characteristics. These findings demonstrate strong discriminative and predictive validity of CHR-P criteria among help-seekers, supporting attenuated psychotic symptoms as a clinically meaningful pre-psychotic phenotype. Results support consideration of APS in DSM-6 within a prognostically grounded, stepped-care framework rather than as a categorical disorder.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world treatment patterns, healthcare resource utilization and economic burden in U.S. adults with schizophrenia with and without tardive dyskinesia.","authors":"Rashmi Patel, Doyoung Kim, Weihua Gao, Ayaan Khan, Talynn Scott, Matthew Sidovar, Kristin Gillard","doi":"10.1038/s41537-026-00780-9","DOIUrl":"https://doi.org/10.1038/s41537-026-00780-9","url":null,"abstract":"<p><p>Tardive dyskinesia (TD) is a persistent, iatrogenic movement disorder arising from long-term use of dopamine receptor antagonists, particularly antipsychotics; however, its clinical and economic impact among adults with schizophrenia remains poorly characterized in real-world settings. This retrospective, matched-cohort analysis used two large U.S. claims databases (PharMetrics Plus and MarketScan Medicaid) to evaluate treatment patterns, healthcare resource utilization (HCRU), and costs among adults with schizophrenia with and without TD. Patients were propensity score matched 1:5 for age, sex, index year, and comorbidity burden. TD was identified in 2.2-2.6% of records, with affected patients being older, more often female, and exhibiting greater medical complexity than those without TD. Following matching, TD was associated with greater use of higher-risk antipsychotic regimens, including nearly double the use of first-generation agents and long-acting injectables, and a twofold to fourfold greater anticholinergic burden. Adherence to antipsychotic therapy was comparable between groups. Across both databases, patients with TD demonstrated substantially greater HCRU and costs, with all-cause expenditures elevated by 56-66% and schizophrenia-related costs by 49-103% versus patients without TD. Approximately one in five individuals with TD received a vesicular monoamine transporter 2 inhibitor, with these patients exhibiting the highest HCRU and costs, suggesting greater disease burden and treatment intensity. TD imposes a considerable clinical and economic burden in schizophrenia underscoring the need for earlier recognition, evidence-based treatment, and preventative strategies, including rational antipsychotic selection and proactive monitoring, to mitigate the long-term impact of TD.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"East Asian herbal medicine as an adjunctive treatment for schizophrenia: a systematic review and meta-analysis.","authors":"Yujin Choi, Pyung-Wha Kim, Chan-Young Kwon, Min-Jae Kim, Kyoung-Eun Lee, Suha Lee, Suyeon Hwang, Ji-Won Kim, Ji-Won Oh, Hye-Li Jeon, Yunna Kim, Boram Lee, Seung-Hun Cho","doi":"10.1038/s41537-026-00781-8","DOIUrl":"https://doi.org/10.1038/s41537-026-00781-8","url":null,"abstract":"<p><strong>Background: </strong>Herbal medicine is widely used as an adjunctive treatment for schizophrenia, but evidence remains limited.</p><p><strong>Aims: </strong>To evaluate the effectiveness and safety of East Asian herbal medicine combined with antipsychotics in schizophrenia spectrum disorders.</p><p><strong>Methods: </strong>Ten sources including MEDLINE, EMBASE and CENTRAL were searched up to January 2025 for randomised controlled trials comparing East Asian herbal medicine combined with antipsychotics versus antipsychotics alone. Primary outcome was the overall symptom scores (PANSS/BPRS). Secondary outcomes included adverse events, negative and positive symptom scores, response rates, social function, quality of life, recurrence, and adherence. Risk of bias was assessed using the Cochrane RoB 2, and evidence certainty using GRADE.</p><p><strong>Results: </strong>270 studies comprising 26,053 participants were included. East Asian herbal medicine combined with standard-dose antipsychotics improved overall symptom (SMD - 1.38, 95% CI - 1.60 to -1.17; 181 studies, 18,569 participants; low-certainty evidence) and reduced adverse events (RR 0.56, 95% CI 0.51-0.62; 92 studies, 8983 participants; low-certainty evidence) versus antipsychotics alone. East Asian herbal medicine combined with low-dose antipsychotics versus standard-dose antipsychotics showed symptom improvement (SMD - 0.92, 95% CI - 1.54- - 0.29; 25 studies, 1907 participants; low-certainty evidence) and fewer adverse events (RR 0.44, 95% CI 0.34-0.58; 6 studies, 450 participants; low-certainty evidence).</p><p><strong>Conclusion: </strong>Low-certainty evidence suggests that East Asian herbal medicine as an adjunct to antipsychotics may improve symptoms and reduce adverse events in schizophrenia. However, most studies raised concerns regarding the risk of bias, and potential publication bias was suspected. Results require cautious interpretation and further high-quality studies are needed.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148427172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}