Schizophrenia (Heidelberg, Germany)最新文献

{"title":"Persistent negative symptoms in the EULAST cohort: impact on functional outcome.","authors":"Luigi Giuliani, Pasquale Pezzella, Giulia M Giordano, Andrea Perrottelli, Armida Mucci, Paola Bucci, Istvan Bitter, Celso Arango, Jurjen J Luykx, Covadonga M Díaz-Caneja, Bjørn H Ebdrup, Michael Davidson, Jari Tiihonen, Inge Winter-van Rossum, Silvana Galderisi","doi":"10.1038/s41537-026-00739-w","DOIUrl":"10.1038/s41537-026-00739-w","url":null,"abstract":"<p><p>Persistent negative symptoms (PNS), defined as negative symptoms of at least moderate severity that endure over time and are not attributable to other psychopathological dimensions such as depression or parkinsonism, have been associated with poor functional outcomes in schizophrenia, in both chronic stages and in the early phases of the disorder. This post-hoc analysis of a large cohort of schizophrenia spectrum disorder patients within their first 7 years of illness, enrolled in the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST), aimed to: 1) confirm prior findings about the prevalence and clinical impact of unconfounded persistent negative symptoms (PNS) on dropout rates and psychosocial functioning after 12 and 18 months of treatment; and 2) explore the prevalence of enduring negative symptoms (E-NS), defined as persistent negative symptoms either confounded or unconfounded by depression or parkinsonism, and their influence on functional outcome. At week 0, 60.6% of patients exhibited at least one negative symptom of moderate severity. Among them, 42.8% met criteria for unconfounded negative symptoms. After 1 year, the frequency of PNS and E-NS was 7.9% and 15%, respectively, with a prospective consistency around 32%. PNS subjects had similar levels of functioning at week 0 (d = -0.179, p = 0.194), but worse functioning after 12 (d = -0.697, p = 0.028) and 18 (d = -0.676, p = 0.024) months of treatment, as compared to those with negative symptoms of similar severity at baseline that did not persist (non-persistent negative symptoms, N-PNS). No difference among groups was observed in drop-out rates. The comparison between the E-NS and N-PNS groups revealed the same functional outcome differences observed in the PNS versus N-PNS comparison. Our findings confirm that long-term persistence of negative symptoms, both primary and secondary, contributes to poor functional outcome. Future research should focus on identifying predictors of symptom persistence to guide the development of targeted interventions aimed at improving long-term functional outcomes in this patient population.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328360","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":"Author Correction: Semantic memory disorganization linked to social functioning in patients with schizophrenia.","authors":"Ayumu Wada, Chika Sumiyoshi, Naoki Yoshimura, Ryota Hashimoto, Junya Matsumoto, Andrew Stickley, Yuji Yamada, Akiko Kikuchi, Ryotaro Kubota, Makoto Matsui, Kana Nakachi, Chinatsu Fujimaki, Leona Adachi, Risa Yamada, Tomiki Sumiyoshi","doi":"10.1038/s41537-026-00740-3","DOIUrl":"10.1038/s41537-026-00740-3","url":null,"abstract":"","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147319155","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":"Prevalence of anti-NMDA receptor antibodies among adult patients presenting with first-episode psychosis in Hong Kong.","authors":"Steven Wai Ho Chau, Charis Kw Lam, Matthew Pm Yu, Joseph Ch Choi, Howan Hw Leung","doi":"10.1038/s41537-026-00741-2","DOIUrl":"10.1038/s41537-026-00741-2","url":null,"abstract":"<p><p>Studies on the presence of anti-NMDA receptor antibodies were done primarily on the European population. This study investigates the prevalence of anti-NMDA antibodies among adult patients presenting with first-onset psychosis in an acute medical setting in the predominantly Chinese population of Hong Kong (n = 109), and our results suggest that such prevalence is low in this population (1.8%), especially among patients with primary psychotic disorders (0%). Further studies are needed to explore the ethnic variation in anti-NMDA receptor positivity.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13057035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313241","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":"Differential DNA-methylation of synaptic genes in CSF and blood in schizophrenia.","authors":"Kirsten Jahn, Adrian Groh, Ole Riemer, Sunyu Sun, Nicole Moschny, Stefan Bleich, Helge Frieling, Franz Felix Konen, Thomas Skripuletz","doi":"10.1038/s41537-026-00738-x","DOIUrl":"10.1038/s41537-026-00738-x","url":null,"abstract":"<p><p>The dual-hit model of schizophrenic psychoses suggests that epigenetic alterations may contribute to the disease pathogenesis. Given the significant synaptic loss in patients with schizophrenia (SZ) during puberty, we investigated DNA-methylation patterns of key synaptic target molecules: dopamine transporter (DAT), dopamine receptor D2 (DRD2), microtubule-associated protein tau (MAPT), and postsynaptic density protein 95 (PSD95). Analyses were performed in both blood and cerebrospinal fluid (CSF) samples from patients with SZ (n = 36) and healthy controls (Co) (n = 23). Due to the minimal amount of cell-free DNA available in CSF, different extraction methods were evaluated to achieve the best possible recovery. Ultimately, an adapted ethanol-glycogen precipitation protocol combined with a subsequent bead-based fusion and DNA clean-up was applied. However, despite comparable DNA concentrations obtained from Co and SZ CSF samples, only very few sequences could be obtained from CSF samples of Co, so that results concerning CSF measurements are limited to patients with SZ. In DAT, methylation was significantly higher in the blood of Co compared to both the blood and CSF of patients with SZ. In PSD95, mean methylation levels were higher in the CSF than in the blood of patients with SZ, whereas no difference was detected in the blood between SZ and Co. For MAPT and DRD2, no significant differences in mean methylation rates were observed between groups. Low sequencing success in CSF from Co, despite comparable concentrations to SZ, might point to a higher degree of fragmentation. In SZ, longer DNA fragments may be replenished more frequently. Higher central methylation of PSD95 in patients with SZ, a key regulator of glutamatergic neurotransmission, may reduce gene transcription and thus support the glutamate hypothesis of SZ, which assumes impaired glutamate receptor function. Lower DAT methylation in SZ compared to Co (with similar central and peripheral levels) could indicate a higher availability of the transporter at the synapse in SZ, resulting in a higher clearance of dopamine. This could be a compensatory mechanism concerning the hypothesis of dopaminergic hyperactivity in SZ.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12993050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260403","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":"Efficacy of an emotion-oriented cognitive behavior therapy for delusions (CBTd-E) compared to waitlist in a single-blinded randomized-controlled trial.","authors":"Stephanie Mehl, Christopher Hautmann, Björn Schlier, Laura Marie-Louise Dorn, Lea Ludwig, Tobias Teismann, Michael Franz, Winfried Rief, Rudolf Stark, Tania Marie Lincoln","doi":"10.1038/s41537-026-00737-y","DOIUrl":"10.1038/s41537-026-00737-y","url":null,"abstract":"<p><p>Psychological interventions for delusions may be enhanced by targeting their presumed causal factors. An emotion-oriented variant of cognitive behavioral therapy for delusions (CBTd-E), designed to target affect regulation and maladaptive schemata, was evaluated for its effect on delusions. A single-blind, multicenter, randomized, waitlist-controlled trial was conducted in three German outpatient clinics. Ninety-four patients with psychotic disorders and persistent delusions were randomized to 25 individual sessions of CBTd-E over 6 months (n = 47) or waitlist (n = 47). CBTd-E included two modules designed to improve affect regulation and maladaptive schemata. Assessments were performed at baseline (T1), three months (T2), and six months (T3). Regression-based analysis of covariance at T3 in the intent-to-treat sample indicated no significant benefit for the CBT-E group in the primary outcome (Psychotic Symptom Rating Scale delusions subscale, d = -0.45 [CI: 0.36; -1.26]). Regarding secondary outcomes, a significant effect favoring CBTd-E was observed in general psychopathology (d = -0.56), but no effects on positive and negative symptoms, depression, general and social functioning, or antipsychotic dosage. Regarding the proposed target mechanisms, we found improved cognitive reappraisal (d = 0.59), worrying (d = -0.52), quality of sleep (d = -0.49), and self-esteem (d = 0.36). Despite its effect on the suggested target mechanisms, affect regulation and maladaptive schemata, and on general psychopathology, this emotion-focused variant of CBT did not show an effect on delusions. A possible avenue to achieve stronger effects on delusions is to personalize the modularized interventions.Trial registration: Clinicaltrials.gov Identifier: NCT02787135.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215293","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":"Functional network comparative area and topography analysis (FUNCATA) in non-affective psychosis: a replication study.","authors":"Daniel Mamah, ShingShiun Chen, Michael P Harms, Mark Curtis, Fanghong Dong","doi":"10.1038/s41537-026-00736-z","DOIUrl":"10.1038/s41537-026-00736-z","url":null,"abstract":"<p><p>Resting-state fMRI studies consistently demonstrate widespread dysconnectivity in schizophrenia (SZ), yet conventional analytic methods often fail to account for individual variability in functional brain organization. This study utilized individualized assessments of network size and topography to examine functional alterations in early psychosis. MRI data were drawn from the Human Connectome Project - Early Psychosis study (ages 18-34), including 86 individuals with non-affective psychosis (NAP) and 57 healthy controls (HC). Ten large-scale functional networks were delineated using template-matching procedures. Group differences in network size were evaluated using ANOVA, while network topography was examined with vertex-wise chi-square analyses and the Topographic Abnormality Index (TAI). Compared to controls, NAP participants showed significantly larger dorsal attention (DAN) and default mode (DMN) networks, along with a smaller sensorimotor-body (SBN) network (effect sizes d = 0.39-0.48). NAP also exhibited greater topographic abnormalities in the DAN, DMN, and cingulo-opercular (CON) networks. DMN size was inversely related to mania symptoms, antipsychotic treatment duration, and working memory performance, while smaller SBN size was also linked to reduced working memory. A k-means clustering revealed three psychosis biotypes. Biotype 1 had enlarged DAN and language network size, with higher antipsychotic exposure. Biotype 2 showed near-normal network profiles but elevated mood symptoms. Biotype 3 exhibited enlarged DMN/DAN and reduced frontoparietal network size, with prominent negative symptoms. Consistent with prior schizophrenia studies, DAN enlargement was present in early psychosis, suggesting stability across illness stages. Altered DAN and DMN organization may serve as early biomarkers to guide detection and intervention strategies.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215264","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":"Expressive pragmatic language in mood and psychotic disorders: a systematic review and meta-analysis.","authors":"Fiona Meister, Martin Sellier Silva, Gleb Melshin, Chaimaa El Mouslih, Farida Zaher, Roozbeh Sattari, Hsi T Wei, Neyra Mekideche, Valentina Bambini, Alban Voppel, Lena Palaniyappan","doi":"10.1038/s41537-026-00733-2","DOIUrl":"10.1038/s41537-026-00733-2","url":null,"abstract":"<p><p>Pragmatic language impairments-difficulties using language effectively in social contexts-are common in adults suffering from severe mental illnesses (SMIs) such as schizophrenia spectrum disorders (SSD), major depressive disorder (MDD), and bipolar disorder (BD). These impairments hinder social functioning and recovery but have been explored most widely using comprehension tasks, with pragmatic production being poorly described. We undertook a systematic review and meta-analysis of studies assessing expressive pragmatic language in adults with SMIs versus healthy controls. 18 items were tested, including Coherence, Cohesion, Gricean maxims, figurative language, Prosody, and Turn-Taking. The searches were PRISMA-compliant and were conducted in PubMed and Scopus. 51 studies were included; 28 were meta-analyzed. Results showed significant impairments in Cooperativity, Anaphora and Cohesion, moderate impairments in Coherence, and low impairments in Metaphor. No significant moderator was detected. Our results emphasize the need for standardized pragmatic testing and intervention for language production in clinical settings.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198393","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":"Pharmacological rescue of social deficits in rats featuring Disrupted-in-Schizophrenia-1 (DISC1) protein aggregation.","authors":"José Dören, Else Van Gerresheim, Sandra Schäble, Svenja Troßbach, Ann-Christin Langen, Heike Schneider, Werner Steimer, Tobias Kalenscher, Carsten Korth","doi":"10.1038/s41537-026-00729-y","DOIUrl":"10.1038/s41537-026-00729-y","url":null,"abstract":"<p><p>The pharmacological treatment of negative symptoms in schizophrenia remains a major unmet need. Among these, impairments in social functioning - manifesting as reduced adaptability and social withdrawal - are particularly disabling, as they persist beyond remission of positive symptoms and impede social reintegration. To investigate the neurobiological basis of behavioral impairments, we employed the tgDISC1 rat, a translational model overexpressing the human non-mutant Disrupted-in-Schizophrenia-1 (DISC1) gene. This overexpression results in DISC1 protein aggregation and aberrant signaling- molecular features identified in a subset of schizophrenia patients identified by elevated DISC1 aggregates in cerebrospinal fluid. Behaviorally, the tgDISC1 rats exhibited a selective loss of social novelty preference in the 3-Chamber task while maintaining intact social interest, indicating a specific deficit in social adaptability rather than social motivation. Here, we tested whether continuous administration of atypical antipsychotics amisulpride or clozapine would rescue social deficits in tgDISC1 rats. Treatment with amisulpride (0.2 and 0.8 mg/kg/day for two weeks) fully restored social novelty preference, whereas clozapine had no effect. Control tasks for anhedonia, short-term working memory, and explorative behavior confirmed that their phenotype was not secondary to global motivational or cognitive impairments. Together, these findings demonstrate that amisulpride, a selective D2/D3 receptor antagonist, rescues social adaptability deficits linked to aberrant DISC1 signaling. The results also highlight the success of our precision psychiatry approach: the biological definition of a subset of schizophrenia by identifying DISC1 protein aggregates, the generation of a corresponding animal model and a successful pharmacotherapy of a clinically relevant phenotype.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":"16"},"PeriodicalIF":4.1,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12877177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121405","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":"Altered auditory seed-based functional connectivity in other specified schizophrenia spectrum and other psychotic disorder compared to schizophrenia spectrum disorders.","authors":"Woo-Sung Kim, Soyolsaikhan Odkhuu, Eun-Jin Jeon, Ariana Setiani, Ling Li, Fatima Zahra Rami, Keon-Hak Lee, Nam-In Kang, Shahida Nazir, Young-Chul Chung","doi":"10.1038/s41537-025-00708-9","DOIUrl":"10.1038/s41537-025-00708-9","url":null,"abstract":"<p><p>Few neuroimaging studies have examined other specified schizophrenia spectrum and other psychotic disorder (OSSO). We sought to identify features differentiating patients with OSSO from those with schizophrenia spectrum disorders (SSD) and healthy controls (HC) using auditory seed-based functional connectivity (FC) analysis. Patients with OSSO (n = 88), patients with SSD (n = 81), and HC (n = 85), matched for age, sex, and education, underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluation. To reduce heterogeneity of OSSO, individuals with specific subtypes of OSSO, i.e., pure delusion and delusion with attenuated auditory hallucinations (AHs) were only included. Using five auditory seeds, we conducted seed-to-voxel and seed-to-region of interest (ROI) analyses. We also conducted between- and within-network connectivity analyses of 13 networks, and correlations of altered FC with symptomatology were explored. The SSD group showed significantly greater connectivity between the superior temporal gyrus (STG) and precuneus, and between the temporal pole cortex (TP) and precuneus, compared to the OSSO group. Overall auditory seed-based hypoconnectivity and middle temporal gyrus-based hyperconnectivity were observed in both groups compared to HC. In OSSO, hallucination severity was positively associated with insula-putamen connectivity, whereas delusional and negative symptoms showed inverse correlations with TP-insula and STG-Heschl's gyrus connectivity, respectively. In SSD, hallucination severity correlated positively with STG-Heschl's gyrus and TP-insula connectivity whereas negative symptoms correlated negatively with STG-insula connectivity. These findings suggest that there are distinct differences in FC between patients with OSSO and patients with SSD, which supports the proposal that OSSO should be treated as a separate clinical syndrome with distinct neural connectomes. Future research may explore whether interventions targeting these altered connectivity patterns could help reduce the risk of progression from OSSO to SSD.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044457","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 link between GABA levels and P300 abnormalities in schizophrenia spectrum disorders: regional and symptom-based insights.","authors":"Berkhan Karslı, Verena Meisinger, Genc Hasanaj, Marcel S Kallweit, Fanny Dengl, Gizem Vural, Julian Melcher, Maxim Korman, Nicole Klimas, Susanne Schmölz, Antonia Šušnjar, Alexandra Hisch, Lenka Krčmář, Emanuel Boudriot, Joanna Moussiopoulou, Vladislav Yakimov, Oliver Pogarell, Andrea Schmitt, Peter Falkai, Thomas Geyer, Lukas Roell, Elias Wagner, Florian J Raabe, Daniel Keeser","doi":"10.1038/s41537-026-00730-5","DOIUrl":"10.1038/s41537-026-00730-5","url":null,"abstract":"<p><p>According to the excitation-inhibition imbalance theory, GABAergic and glutamatergic systems influence the clinical symptoms, particularly cognitive deficits in schizophrenia spectrum disorders (SSD). These systems have been found disrupted in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) in SSD, and may contribute to P300 abnormalities in electroencephalography recordings. Therefore, we explored the relationships among MRS-derived GABA and Glx levels in the ACC and left DLPFC (lDLPFC), auditory P3b subcomponent amplitudes and latencies, cognition, and symptom severity in SSD. In total, 107 patients and 107 healthy controls (HC) were included in the study, with the exact numbers varying across specific analyses. We grouped patients into higher (SSD+, N = 41) and lower (SSD-, N = 65) symptom severity clusters based on PANSS total scores. P3b amplitudes were lower in SSD patients than HC at central and parietal sites. SSD+ exhibited widespread P3b amplitude reductions, significant at parietal and trend-level at central and frontal regions, while SSD- showed a trend-level amplitude reduction limited to the parietal region. GABA levels in the lDLPFC were higher in SSD- compared to controls and were positively associated with P3b amplitudes at central and parietal sites within SSD- and overall SSD group. Although P3b amplitudes positively correlated with the BACS composite scores and behavioral performance, lDLPFC GABA levels showed no direct association with cognitive or behavioral performance. ACC GABA, ACC Glx, and lDLPFC Glx levels showed no group differences or P3b associations. Our findings suggest P3b amplitude reductions as a marker of cognitive dysfunction in SSD, more pronounced in patients with higher illness severity, and that enhanced lDLPFC GABA may contribute to offsetting these reductions. Our work provides the first empirical evidence of the interplay between the GABAergic system and cortical electrophysiological signal patterns associated with cognitive dysfunction in SSD.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":" ","pages":"11"},"PeriodicalIF":4.1,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12859150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042369","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}