{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:23:33Z","timestamp":1781735013015,"version":"3.54.5"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Schizophr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200941) and lower (SSD\u2212,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200965) 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\u2212 showed a trend-level amplitude reduction limited to the parietal region. GABA levels in the lDLPFC were higher in SSD\u2212 compared to controls and were positively associated with P3b amplitudes at central and parietal sites within SSD\u2212 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.\n                  <\/jats:p>","DOI":"10.1038\/s41537-026-00730-5","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:34:05Z","timestamp":1769189645000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The link between GABA levels and P300 abnormalities in schizophrenia spectrum disorders: regional and symptom-based insights"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0763-1078","authenticated-orcid":false,"given":"Berkhan","family":"Karsl\u0131","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Meisinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9807-1015","authenticated-orcid":false,"given":"Genc","family":"Hasanaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel S.","family":"Kallweit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Dengl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-1879","authenticated-orcid":false,"given":"Gizem","family":"Vural","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Melcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7489-8442","authenticated-orcid":false,"given":"Maxim","family":"Korman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Klimas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Schm\u00f6lz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"\u0160u\u0161njar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Hisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Kr\u010dm\u00e1\u0159","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"CDP Working Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-6318","authenticated-orcid":false,"given":"Emanuel","family":"Boudriot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-6197","authenticated-orcid":false,"given":"Joanna","family":"Moussiopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9559-7492","authenticated-orcid":false,"given":"Vladislav","family":"Yakimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-4190","authenticated-orcid":false,"given":"Oliver","family":"Pogarell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-4023","authenticated-orcid":false,"given":"Andrea","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-8667","authenticated-orcid":false,"given":"Peter","family":"Falkai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Geyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-2290","authenticated-orcid":false,"given":"Lukas","family":"Roell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-6167","authenticated-orcid":false,"given":"Elias","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8538-0783","authenticated-orcid":false,"given":"Florian J.","family":"Raabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0244-1024","authenticated-orcid":false,"given":"Daniel","family":"Keeser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"730_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.67","volume":"1","author":"RS Kahn","year":"2015","unstructured":"Kahn, R. S. et al. Schizophrenia. Nat. Rev. Dis. Prim. 1, 15067 (2015).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"730_CR2","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1038\/s41380-023-01949-9","volume":"28","author":"RA McCutcheon","year":"2023","unstructured":"McCutcheon, R. A., Keefe, R. S. E. & McGuire, P. K. Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment. Mol. Psychiatry 28, 1902\u20131918 (2023).","journal-title":"Mol. Psychiatry"},{"key":"730_CR3","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.schres.2004.01.004","volume":"70","author":"E Bramon","year":"2004","unstructured":"Bramon, E. Meta-analysis of the P300 and P50 waveforms in schizophrenia. Schizophr. Res. 70, 315\u2013329 (2004).","journal-title":"Schizophr. Res."},{"key":"730_CR4","doi-asserted-by":"crossref","unstructured":"Qiu, Y. Q., Tang, Y. X., Chan, R. C. K., Sun, X. Y. & He, J. P300 aberration in first-episode schizophrenia patients: a meta-analysis. Chao L., ed. PLoS ONE 2014;9:e97794.","DOI":"10.1371\/journal.pone.0097794"},{"key":"730_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2024.108757","volume":"187","author":"HK Hamilton","year":"2024","unstructured":"Hamilton, H. K., Mathalon, D. H. & Ford, J. M. P300 in schizophrenia: then and now. Biol. Psychol. 187, 108757 (2024).","journal-title":"Biol. Psychol."},{"key":"730_CR6","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S0149-7634(01)00019-7","volume":"25","author":"D Friedman","year":"2001","unstructured":"Friedman, D., Cycowicz, Y. M. & Gaeta, H. The novelty P3: an event-related brain potential (ERP) sign of the brain\u2019s evaluation of novelty. Neurosci. Biobehav. Rev. 25, 355\u2013373 (2001).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"730_CR7","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1093\/brain\/123.5.927","volume":"123","author":"KR Daffner","year":"2000","unstructured":"Daffner, K. R. et al. The central role of the prefrontal cortex in directing attention to novel events. Brain 123, 927\u2013939 (2000).","journal-title":"Brain"},{"key":"730_CR8","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/0013-4694(75)90263-1","volume":"38","author":"NK Squires","year":"1975","unstructured":"Squires, N. K., Squires, K. C. & Hillyard, S. A. Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man. Electroencephalogr. Clin. Neurophysiol. 38, 387\u2013401 (1975).","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"730_CR9","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1016\/j.clinph.2007.04.019","volume":"118","author":"J Polich","year":"2007","unstructured":"Polich, J. Updating P300: an integrative theory of P3a and P3b. Clin. Neurophysiol. 118, 2128\u20132148 (2007).","journal-title":"Clin. Neurophysiol."},{"key":"730_CR10","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/S0006-3223(98)00290-X","volume":"46","author":"JM Ford","year":"1999","unstructured":"Ford, J. M. et al. P300 amplitude is related to clinical state in severely and moderately ill patients with schizophrenia. Biol. Psychiatry 46, 94\u2013101 (1999).","journal-title":"Biol. Psychiatry"},{"key":"730_CR11","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/S0006-3223(99)00277-2","volume":"47","author":"DH Mathalon","year":"2000","unstructured":"Mathalon, D. H., Ford, J. M. & Pfefferbaum, A. Trait and state aspects of p300 amplitude reduction in schizophrenia: a retrospective longitudinal study. Biol. Psychiatry 47, 434\u2013449 (2000).","journal-title":"Biol. Psychiatry"},{"key":"730_CR12","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/S0013-4694(97)00119-3","volume":"106","author":"E Halgren","year":"1998","unstructured":"Halgren, E., Marinkovic, K. & Chauvel, P. Generators of the late cognitive potentials in auditory and visual oddball tasks. Electroencephalogr. Clin. Neurophysiol. 106, 156\u2013164 (1998).","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"730_CR13","doi-asserted-by":"publisher","first-page":"51","DOI":"10.55782\/ane-2012-1880","volume":"72","author":"E Wronka","year":"2012","unstructured":"Wronka, E., Kaiser, J. & Coenen, A. Neural generators of the auditory evoked potential components P3a and P3b. Acta Neurobiol. Exp. (Warsz.) 72, 51\u201364 (2012).","journal-title":"Acta Neurobiol. Exp. (Warsz.)"},{"key":"730_CR14","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.neuroimage.2006.12.020","volume":"35","author":"M Br\u00e1zdil","year":"2007","unstructured":"Br\u00e1zdil, M., Mikl, M., Mare\u010dek, R., Krupa, P. & Rektor, I. Effective connectivity in target stimulus processing: a dynamic causal modeling study of visual oddball task. NeuroImage 35, 827\u2013835 (2007).","journal-title":"NeuroImage"},{"key":"730_CR15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3389\/fncom.2018.00033","volume":"12","author":"F Li","year":"2018","unstructured":"Li, F. et al. Top-down disconnectivity in schizophrenia during P300 tasks. Front Comput Neurosci. 12, 33 (2018).","journal-title":"Front Comput Neurosci."},{"key":"730_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2021.645209","volume":"15","author":"I Hertrich","year":"2021","unstructured":"Hertrich, I., Dietrich, S., Blum, C. & Ackermann, H. The role of the dorsolateral prefrontal cortex for speech and language processing. Front. Hum. Neurosci. 15, 645209 (2021).","journal-title":"Front. Hum. Neurosci."},{"key":"730_CR17","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1093\/cercor\/bhn117","volume":"19","author":"AMC Kelly","year":"2009","unstructured":"Kelly, A. M. C. et al. Development of anterior cingulate functional connectivity from late childhood to early adulthood. Cereb. Cortex 19, 640\u2013657 (2009).","journal-title":"Cereb. Cortex"},{"key":"730_CR18","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1001\/archgenpsychiatry.2009.91","volume":"66","author":"MJ Minzenberg","year":"2009","unstructured":"Minzenberg, M. J., Laird, A. R., Thelen, S., Carter, C. S. & Glahn, D. C. Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Arch. Gen. Psychiatry 66, 811 (2009).","journal-title":"Arch. Gen. Psychiatry"},{"key":"730_CR19","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1017\/S0033291721005523","volume":"52","author":"M Pic\u00f3-P\u00e9rez","year":"2022","unstructured":"Pic\u00f3-P\u00e9rez, M. et al. Multimodal meta-analysis of structural gray matter, neurocognitive and social cognitive fMRI findings in schizophrenia patients. Psychol. Med. 52, 614\u2013624 (2022).","journal-title":"Psychol. Med."},{"key":"730_CR20","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.biopsych.2018.11.011","volume":"85","author":"Z Sha","year":"2019","unstructured":"Sha, Z., Wager, T. D., Mechelli, A. & He, Y. Common dysfunction of large-scale neurocognitive networks across psychiatric disorders. Biol. Psychiatry 85, 379\u2013388 (2019).","journal-title":"Biol. Psychiatry"},{"key":"730_CR21","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/s41386-021-01089-0","volume":"47","author":"J Smucny","year":"2022","unstructured":"Smucny, J., Dienel, S. J., Lewis, D. A. & Carter, C. S. Mechanisms underlying dorsolateral prefrontal cortex contributions to cognitive dysfunction in schizophrenia. Neuropsychopharmacology 47, 292\u2013308 (2022).","journal-title":"Neuropsychopharmacology"},{"key":"730_CR22","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s00406-018-0877-3","volume":"269","author":"V Molina","year":"2019","unstructured":"Molina, V. et al. Topography of activation deficits in schizophrenia during P300 task related to cognition and structural connectivity. Eur. Arch. Psychiatry Clin. Neurosci. 269, 419\u2013428 (2019).","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"730_CR23","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.656","volume":"7","author":"I Karton","year":"2017","unstructured":"Karton, I. & Bachmann, T. Disrupting dorsolateral prefrontal cortex by rTMS reduces the P300 based marker of deception. Brain Behav. 7, e00656 (2017).","journal-title":"Brain Behav."},{"key":"730_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.664535","volume":"9","author":"Y Liu","year":"2021","unstructured":"Liu, Y. et al. A selective review of the excitatory-inhibitory imbalance in schizophrenia: underlying biology, genetics, microcircuits, and symptoms. Front. Cell Dev. Biol. 9, 664535 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"730_CR25","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/s41380-021-01297-6","volume":"27","author":"T Nakahara","year":"2022","unstructured":"Nakahara, T. et al. Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of 1H-magnetic resonance spectroscopy studies. Mol. Psychiatry 27, 744\u2013757 (2022).","journal-title":"Mol. Psychiatry"},{"key":"730_CR26","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.biopsych.2021.06.008","volume":"90","author":"J Smucny","year":"2021","unstructured":"Smucny, J., Carter, C. S. & Maddock, R. J. Medial prefrontal cortex glutamate is reduced in schizophrenia and moderated by measurement quality: a meta-analysis of proton magnetic resonance spectroscopy studies. Biol. Psychiatry 90, 643\u2013651 (2021).","journal-title":"Biol. Psychiatry"},{"key":"730_CR27","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1001\/jamapsychiatry.2021.0380","volume":"78","author":"K Merritt","year":"2021","unstructured":"Merritt, K. et al. Association of age, antipsychotic medication, and symptom severity in schizophrenia with proton magnetic resonance spectroscopy brain glutamate level: a mega-analysis of individual participant-level data. JAMA Psychiatry 78, 667 (2021).","journal-title":"JAMA Psychiatry"},{"key":"730_CR28","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1038\/s41380-023-01991-7","volume":"28","author":"K Merritt","year":"2023","unstructured":"Merritt, K. et al. Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis. Mol. Psychiatry 28, 2039\u20132048 (2023).","journal-title":"Mol. Psychiatry"},{"key":"730_CR29","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.biopsych.2022.08.004","volume":"93","author":"M Simmonite","year":"2023","unstructured":"Simmonite, M., Steeby, C. J. & Taylor, S. F. Medial frontal cortex GABA concentrations in psychosis spectrum and mood disorders: a meta-analysis of proton magnetic resonance spectroscopy studies. Biol. Psychiatry 93, 125\u2013136 (2023).","journal-title":"Biol. Psychiatry"},{"key":"730_CR30","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.tins.2011.10.004","volume":"35","author":"DA Lewis","year":"2012","unstructured":"Lewis, D. A., Curley, A. A., Glausier, J. R. & Volk, D. W. Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci. 35, 57\u201367 (2012).","journal-title":"Trends Neurosci."},{"key":"730_CR31","first-page":"395","volume":"26","author":"ER Marcotte","year":"2001","unstructured":"Marcotte, E. R., Pearson, D. M. & Srivastava, L. K. Animal models of schizophrenia: a critical review. J. Psychiatry Neurosci. 26, 395\u2013410 (2001).","journal-title":"J. Psychiatry Neurosci."},{"key":"730_CR32","doi-asserted-by":"publisher","first-page":"e1147","DOI":"10.1038\/tp.2017.124","volume":"7","author":"A Egerton","year":"2017","unstructured":"Egerton, A., Modinos, G., Ferrera, D. & McGuire, P. Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis. Transl. Psychiatry 7, e1147\u2013e1147 (2017).","journal-title":"Transl. Psychiatry"},{"key":"730_CR33","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.biopsych.2020.09.001","volume":"89","author":"J Kaminski","year":"2021","unstructured":"Kaminski, J. et al. Glutamate in the dorsolateral prefrontal cortex in patients with schizophrenia: a meta-analysis of 1H-magnetic resonance spectroscopy studies. Biol. Psychiatry 89, 270\u2013277 (2021).","journal-title":"Biol. Psychiatry"},{"key":"730_CR34","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.neuroimage.2015.02.014","volume":"111","author":"MH Hall","year":"2015","unstructured":"Hall, M. H. et al. Frontal P3 event-related potential is related to brain glutamine\/glutamate ratio measured in vivo. NeuroImage 111, 186\u2013191 (2015).","journal-title":"NeuroImage"},{"key":"730_CR35","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s00213-006-0397-0","volume":"187","author":"J Gallinat","year":"2006","unstructured":"Gallinat, J. et al. Hippocampal glutamate concentration predicts cerebral theta oscillations during cognitive processing. Psychopharmacol. (Berl.) 187, 103\u2013111 (2006).","journal-title":"Psychopharmacol. (Berl.)"},{"key":"730_CR36","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1179811","volume":"14","author":"L Kr\u010dm\u00e1\u0159","year":"2023","unstructured":"Kr\u010dm\u00e1\u0159, L. et al. The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research. Front. Psychiatry 14, 1179811 (2023).","journal-title":"Front. Psychiatry"},{"key":"730_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.934640","volume":"13","author":"JL Kalman","year":"2022","unstructured":"Kalman, J. L. et al. Biobanking in everyday clinical practice in psychiatry\u2014The Munich Mental Health Biobank. Front Psychiatry 13, 934640 (2022).","journal-title":"Front Psychiatry"},{"key":"730_CR38","first-page":"22","volume":"59","author":"DV Sheehan","year":"1998","unstructured":"Sheehan, D. V. et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59, 22\u201333 (1998).","journal-title":"J. Clin. Psychiatry"},{"key":"730_CR39","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1093\/schbul\/13.2.261","volume":"13","author":"SR Kay","year":"1987","unstructured":"Kay, S. R., Fiszbein, A. & Opler, L. A. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr. Bull. 13, 261\u2013276 (1987).","journal-title":"Schizophr. Bull."},{"key":"730_CR40","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.schres.2003.09.011","volume":"68","author":"RSE Keefe","year":"2004","unstructured":"Keefe, R. S. E. et al. The brief assessment of cognition in schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr. Res. 68, 283\u2013297 (2004).","journal-title":"Schizophr. Res."},{"key":"730_CR41","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jneumeth.2003.10.009","volume":"134","author":"A Delorme","year":"2004","unstructured":"Delorme, A. & Makeig, S. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J. Neurosci. Methods 134, 9\u201321 (2004).","journal-title":"J. Neurosci. Methods"},{"key":"730_CR42","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.biopsych.2021.07.024","volume":"91","author":"RA Adams","year":"2022","unstructured":"Adams, R. A. et al. Computational modeling of electroencephalography and functional magnetic resonance imaging paradigms indicates a consistent loss of pyramidal cell synaptic gain in schizophrenia. Biol. Psychiatry 91, 202\u2013215 (2022).","journal-title":"Biol. Psychiatry"},{"key":"730_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/1744-9081-7-30","volume":"7","author":"I Winkler","year":"2011","unstructured":"Winkler, I., Haufe, S. & Tangermann, M. Automatic classification of artifactual ICA-components for artifact removal in EEG signals. Behav. Brain Funct. 7, 30 (2011).","journal-title":"Behav. Brain Funct."},{"key":"730_CR44","doi-asserted-by":"publisher","first-page":"035013","DOI":"10.1088\/1741-2560\/11\/3\/035013","volume":"11","author":"I Winkler","year":"2014","unstructured":"Winkler, I. et al. Robust artifactual independent component classification for BCI practitioners. J. Neural Eng. 11, 035013 (2014).","journal-title":"J. Neural Eng."},{"key":"730_CR45","doi-asserted-by":"publisher","unstructured":"Gramfort A. MEG and EEG data analysis with MNE-Python. Front Neurosci. 7 https:\/\/doi.org\/10.3389\/fnins.2013.00267 (2013).","DOI":"10.3389\/fnins.2013.00267"},{"key":"730_CR46","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1002\/mrm.24131","volume":"68","author":"A Andreychenko","year":"2012","unstructured":"Andreychenko, A., Boer, V. O., Arteaga De Castro, C. S., Luijten, P. R. & Klomp, D. W. J. Efficient spectral editing at 7 T: GABA detection with MEGA-sLASER. Magn. Reson Med. 68, 1018\u20131025 (2012).","journal-title":"Magn. Reson Med."},{"key":"730_CR47","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1002\/mrm.22708","volume":"65","author":"G \u00d6z","year":"2011","unstructured":"\u00d6z, G. & Tk\u00e1\u010d, I. Short-echo, single-shot, full-intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: Validation in the cerebellum and brainstem. Magn. Reson. Med. 65, 901\u2013910 (2011).","journal-title":"Magn. Reson. Med."},{"key":"730_CR48","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1002\/(SICI)1099-1492(199810)11:6<266::AID-NBM530>3.0.CO;2-J","volume":"11","author":"M Mescher","year":"1998","unstructured":"Mescher, M., Merkle, H., Kirsch, J., Garwood, M. & Gruetter, R. Simultaneous in vivo spectral editing and water suppression. NMR Biomed. 11, 266\u2013272 (1998).","journal-title":"NMR Biomed."},{"key":"730_CR49","doi-asserted-by":"publisher","first-page":"5662","DOI":"10.1073\/pnas.90.12.5662","volume":"90","author":"DL Rothman","year":"1993","unstructured":"Rothman, D. L., Petroff, O. A., Behar, K. L. & Mattson, R. H. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc. Natl. Acad. Sci. 90, 5662\u20135666 (1993).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"730_CR50","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.pscychresns.2018.07.003","volume":"279","author":"RJ Maddock","year":"2018","unstructured":"Maddock, R. J., Caton, M. D. & Ragland, J. D. Estimating glutamate and Glx from GABA-optimized MEGA-PRESS: Off-resonance but not difference spectra values correspond to PRESS values. Psychiatry Res. Neuroimaging 279, 22\u201330 (2018).","journal-title":"Psychiatry Res. Neuroimaging"},{"key":"730_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2020.108827","volume":"343","author":"G Oeltzschner","year":"2020","unstructured":"Oeltzschner, G. et al. Osprey: Open-source processing, reconstruction & estimation of magnetic resonance spectroscopy data. J. Neurosci. Methods 343, 108827 (2020).","journal-title":"J. Neurosci. Methods"},{"key":"730_CR52","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1002\/mrm.1910300604","volume":"30","author":"SW Provencher","year":"1993","unstructured":"Provencher, S. W. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn. Reson Med. 30, 672\u2013679 (1993).","journal-title":"Magn. Reson Med."},{"key":"730_CR53","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/mrm.26091","volume":"77","author":"R Simpson","year":"2017","unstructured":"Simpson, R., Devenyi, G. A., Jezzard, P., Hennessy, T. J. & Near, J. Advanced processing and simulation of MRS data using the FID appliance (FID-A)\u2014an open source, MATLAB-based toolkit. Magn. Reson Med. 77, 23\u201333 (2017).","journal-title":"Magn. Reson Med."},{"key":"730_CR54","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B Stat. Methodol. 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"730_CR55","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1002\/jmri.29017","volume":"59","author":"NA John","year":"2024","unstructured":"John, N. A. et al. Longitudinal metabolite changes in progressive multiple sclerosis: a study of 3 potential neuroprotective treatments. J. Magn. Reson Imaging 59, 2192\u20132201 (2024).","journal-title":"J. Magn. Reson Imaging"},{"key":"730_CR56","doi-asserted-by":"publisher","unstructured":"Hall, P. The Bootstrap and Edgeworth Expansion (Springer New York, 1992). https:\/\/doi.org\/10.1007\/978-1-4612-4384-7.","DOI":"10.1007\/978-1-4612-4384-7"},{"key":"730_CR57","doi-asserted-by":"crossref","unstructured":"Thulin, M. Modern Statistics with R: From Wrangling and Exploring Data to Inference and Predictive Modelling 2nd edn. (CRC Press, Taylor & Francis Group, 2024).","DOI":"10.1201\/9781003401339"},{"key":"730_CR58","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1002\/bimj.201100065","volume":"53","author":"I Funatogawa","year":"2011","unstructured":"Funatogawa, I. & Funatogawa, T. Analysis of covariance with pre-treatment measurements in randomized trials: Comparison of equal and unequal slopes. Biom. J. 53, 810\u2013821 (2011).","journal-title":"Biom. J."},{"key":"730_CR59","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1001\/archgenpsychiatry.2011.1519","volume":"69","author":"LS Kegeles","year":"2012","unstructured":"Kegeles, L. S., Mao, X. & Stanford, A. D. Elevated prefrontal cortex \u03b3-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch. Gen. Psychiatry 69, 449 (2012).","journal-title":"Arch. Gen. Psychiatry"},{"key":"730_CR60","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3389\/fpsyt.2017.00118","volume":"8","author":"JC De Jonge","year":"2017","unstructured":"De Jonge, J. C., Vinkers, C. H., Hulshoff Pol, H. E. & Marsman, A. GABAergic mechanisms in schizophrenia: linking postmortem and in vivo studies. Front Psychiatry 8, 118 (2017).","journal-title":"Front Psychiatry"},{"key":"730_CR61","doi-asserted-by":"crossref","unstructured":"Reinsel, R. A. et al. Effect of midazolam on the auditory event-related potential: measures of selective attention. Anesth Analg. 73, 612\u2013618 (1991).","DOI":"10.1213\/00000539-199111000-00017"},{"key":"730_CR62","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/0013-4694(91)90114-J","volume":"78","author":"B Rockstroh","year":"1991","unstructured":"Rockstroh, B., Elbert, T., Lutzenberger, W. & Altenm\u00fcller, E. Effects of the anticonvulsant benzodiazepine clonazepam on event-related brain potentials in humans. Electroencephalogr. Clin. Neurophysiol. 78, 142\u2013149 (1991).","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"730_CR63","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1017\/S1461145708009334","volume":"12","author":"TD Watson","year":"2009","unstructured":"Watson, T. D. et al. Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission. Int J. Neuropsychopharmacol. 12, 357 (2009).","journal-title":"Int J. Neuropsychopharmacol."},{"key":"730_CR64","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1093\/cercor\/bhs370","volume":"24","author":"JD Murray","year":"2014","unstructured":"Murray, J. D. et al. Linking microcircuit dysfunction to cognitive impairment: effects of disinhibition associated with schizophrenia in a cortical working memory model. Cereb. Cortex 24, 859\u2013872 (2014).","journal-title":"Cereb. Cortex"},{"key":"730_CR65","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.biopsych.2016.05.022","volume":"81","author":"GD Hoftman","year":"2017","unstructured":"Hoftman, G. D., Datta, D. & Lewis, D. A. Layer 3 excitatory and inhibitory circuitry in the prefrontal cortex: developmental trajectories and alterations in schizophrenia. Biol. Psychiatry 81, 862\u2013873 (2017).","journal-title":"Biol. Psychiatry"},{"key":"730_CR66","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1177\/0004867419898520","volume":"54","author":"H Cen","year":"2020","unstructured":"Cen, H. et al. Neurochemical and brain functional changes in the ventromedial prefrontal cortex of first-episode psychosis patients: a combined functional magnetic resonance imaging\u2014proton magnetic resonance spectroscopy study. Aust. N. Z. J. Psychiatry 54, 519\u2013527 (2020).","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"730_CR67","doi-asserted-by":"publisher","first-page":"pyv105","DOI":"10.1093\/ijnp\/pyv105","volume":"19","author":"C De La Fuente-Sandoval","year":"2016","unstructured":"De La Fuente-Sandoval, C. et al. Cortico-striatal GABAergic and glutamatergic dysregulations in subjects at ultra-high risk for psychosis investigated with proton magnetic resonance spectroscopy. Int J. Neuropsychopharmacol. 19, pyv105 (2016).","journal-title":"Int J. Neuropsychopharmacol."},{"key":"730_CR68","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1001\/jamapsychiatry.2023.3157","volume":"80","author":"F Reyes-Madrigal","year":"2023","unstructured":"Reyes-Madrigal, F. et al. Prefrontal \u03b3-aminobutyric acid levels in never-medicated individuals with chronic schizophrenia. JAMA Psychiatry 80, 1075 (2023).","journal-title":"JAMA Psychiatry"},{"key":"730_CR69","first-page":"341","volume":"27","author":"Z Yang","year":"2015","unstructured":"Yang, Z. et al. Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls. Shanghai Arch. Psychiatry 27, 341\u2013347 (2015).","journal-title":"Shanghai Arch. Psychiatry"},{"key":"730_CR70","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.biopsych.2010.05.016","volume":"68","author":"D \u00d6ng\u00fcr","year":"2010","unstructured":"\u00d6ng\u00fcr, D., Prescot, A. P., McCarthy, J., Cohen, B. M. & Renshaw, P. F. Elevated gamma-aminobutyric acid levels in chronic schizophrenia. Biol. Psychiatry 68, 667\u2013670 (2010).","journal-title":"Biol. Psychiatry"},{"key":"730_CR71","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.biopsych.2017.09.028","volume":"83","author":"C De La Fuente-Sandoval","year":"2018","unstructured":"De La Fuente-Sandoval, C. et al. Prefrontal and striatal gamma-aminobutyric acid levels and the effect of antipsychotic treatment in first-episode psychosis patients. Biol. Psychiatry 83, 475\u2013483 (2018).","journal-title":"Biol. Psychiatry"},{"key":"730_CR72","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23284-9","volume":"12","author":"JA Cooper","year":"2021","unstructured":"Cooper, J. A. et al. Reduced adaptation of glutamatergic stress response is associated with pessimistic expectations in depression. Nat. Commun. 12, 3166 (2021).","journal-title":"Nat. Commun."},{"key":"730_CR73","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1002\/brb3.74","volume":"2","author":"L Schmaal","year":"2012","unstructured":"Schmaal, L., Goudriaan, A. E., Van Der Meer, J., Van Den Brink, W. & Veltman, D. J. The association between cingulate cortex glutamate concentration and delay discounting is mediated by resting state functional connectivity. Brain Behav. 2, 553\u2013562 (2012).","journal-title":"Brain Behav."},{"key":"730_CR74","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.biopsych.2020.06.027","volume":"89","author":"KB Bojesen","year":"2021","unstructured":"Bojesen, K. B. et al. Associations between cognitive function and levels of glutamatergic metabolites and gamma-aminobutyric acid in antipsychotic-na\u00efve patients with schizophrenia or psychosis. Biol. Psychiatry 89, 278\u2013287 (2021).","journal-title":"Biol. Psychiatry"},{"key":"730_CR75","doi-asserted-by":"publisher","first-page":"e87347","DOI":"10.1371\/journal.pone.0087347","volume":"9","author":"R Van Dinteren","year":"2014","unstructured":"Van Dinteren, R., Arns, M., Jongsma, M. L. A. & Kessels, R. P. C. P300 development across the lifespan: a systematic review and meta-analysis. PLoS ONE 9, e87347 (2014).","journal-title":"PLoS ONE"}],"container-title":["Schizophrenia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41537-026-00730-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41537-026-00730-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41537-026-00730-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:02:56Z","timestamp":1769752976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41537-026-00730-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["730"],"URL":"https:\/\/doi.org\/10.1038\/s41537-026-00730-5","relation":{},"ISSN":["2754-6993"],"issn-type":[{"value":"2754-6993","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]},"assertion":[{"value":"13 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no biomedical financial interests or potential conflicts of interest regarding the content of this report. P.F. received paid speakership by Boehringer-Ingelheim, Janssen, Otsuka, Lundbeck, Recordati, and Richter and was member of advisory boards of these companies. E.W. was invited to advisory boards from Recordati, Teva and Boehringer Ingelheim. Apart from P.F. and E.W., no other member of the CDP Working Group has a conflict of interest to report.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"During the preparation of this work the authors used the GPT \u2013 4 model developed by OpenAI to improve readability and language of the manuscript. After using this tool\/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies in the writing process"}}],"article-number":"11"}}