{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:35:37Z","timestamp":1793140537252,"version":"4.5.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L010305\/1"],"award-info":[{"award-number":["MR\/L010305\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P005748\/1"],"award-info":[{"award-number":["MR\/P005748\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/Y004094\/1"],"award-info":[{"award-number":["MR\/Y004094\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH124873"],"award-info":[{"award-number":["R01MH124873"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent genomic research, considered in the wider context of knowledge from outside genomics, provides significant conceptual insights into the aetiology and pathogenesis of schizophrenia. The evidence indicates that genetic risk is expressed across the lifespan, from foetal development through to adulthood, and involves multiple neuronal types and brain regions. Schizophrenia appears to be primarily a neuronal disorder, with synaptic dysfunction playing a central role in pathogenesis both during development and in mature adult brain function, alongside earlier non-synaptic neurodevelopmental mechanisms. Importantly, non-familial genetic and environmental factors substantially influence neurodevelopmental impairment, and this is often reflected in cognitive performance falling below familial expectations. Cognitive deficits and structural brain abnormalities are weakly correlated with familial genetic risk and are better understood as markers of neurodevelopmental vulnerability rather than causal mediators. Genomic findings also position schizophrenia within a neurodevelopmental continuum, spanning childhood-onset disorders to adult-onset psychiatric conditions, and suggest heterogeneity within schizophrenia, with some cases exhibiting stronger neurodevelopmental involvement. These findings challenge notions that schizophrenia can be ascribed to, or understood by studying, dysfunction in particular neuronal types, brain regions or circuits, or to defects at a particular stage of neurodevelopment. While schizophrenia appears to be predominantly a neuronal disorder, pathophysiology appears to be manifest widely across time and space, and in different neuronal types across the adult and foetal brain. Moreover, despite schizophrenia\u2019s high heritability, there is mounting evidence that non-familial genetic and environmental factors play important roles in the neurodevelopmental processes that impact on schizophrenia risk. Finally, variation in the impact of the neurodevelopmental factors appears to be key to understanding some of the heterogeneity within schizophrenia and the relationship between schizophrenia and other conditions. These observations have profound implications for future research, particularly in clarifying pathogenic mechanisms and refining diagnostic frameworks.<\/jats:p>","DOI":"10.1038\/s41380-026-03654-9","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:50:43Z","timestamp":1779331843000},"page":"5727-5733","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rethinking schizophrenia: insights from genomics and implications for research"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-0862","authenticated-orcid":false,"given":"Michael J.","family":"Owen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-2379","authenticated-orcid":false,"given":"Michael C.","family":"O\u2019Donovan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"3654_CR1","doi-asserted-by":"publisher","first-page":"3638","DOI":"10.1038\/s41380-023-02293-8","volume":"28","author":"MJ Owen","year":"2023","unstructured":"Owen MJ, Legge SE, Rees E, Walters JTR, O\u2019Donovan MC. Genomic findings in schizophrenia and their implications. Mol Psychiatry. 2023;28:3638\u201347.","journal-title":"Mol Psychiatry"},{"key":"3654_CR2","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/wps.21034","volume":"22","author":"OA Andreassen","year":"2023","unstructured":"Andreassen OA, Hindley GFL, Frei O, Smeland OB. New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications. World Psychiatry. 2023;22:4\u201324.","journal-title":"World Psychiatry"},{"key":"3654_CR3","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41583-024-00837-7","volume":"25","author":"PF Sullivan","year":"2024","unstructured":"Sullivan PF, Yao S, Hjerling-Leffler J. Schizophrenia genomics: genetic complexity and functional insights. Nat Rev Neurosci. 2024;25:611\u201324.","journal-title":"Nat Rev Neurosci"},{"key":"3654_CR4","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/s41586-022-04434-5","volume":"604","author":"V Trubetskoy","year":"2022","unstructured":"Trubetskoy V, Pardi\u00f1as AF, Qi T, Panagiotaropoulou G, Awasthi S, Bigdeli TB, et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature. 2022;604:502\u20138.","journal-title":"Nature"},{"key":"3654_CR5","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1001\/jamapsychiatry.2024.0036","volume":"81","author":"KS Kendler","year":"2024","unstructured":"Kendler KS. Are psychiatric disorders brain diseases?-a new look at an old question. JAMA Psychiatry. 2024;81:325\u20136.","journal-title":"JAMA Psychiatry"},{"key":"3654_CR6","doi-asserted-by":"crossref","unstructured":"Owen MJ, Bray NJ, Walters JTR, O\u2019Donovan MC. Genomics of schizophrenia, bipolar disorder and major depressive disorder. Nat Rev Genet. 2025.","DOI":"10.1038\/s41576-025-00843-0"},{"key":"3654_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55611-1","volume":"16","author":"S Yao","year":"2025","unstructured":"Yao S, Harder A, Darki F, Chang YW, Li A, Nikouei K, et al. Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity. Nat Commun. 2025;16:395.","journal-title":"Nat Commun"},{"key":"3654_CR8","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/mp.2011.154","volume":"17","author":"G Kirov","year":"2012","unstructured":"Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M, Ruderfer D, et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry. 2012;17:142\u201353.","journal-title":"Mol Psychiatry"},{"key":"3654_CR9","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.biopsych.2014.07.011","volume":"77","author":"J Hall","year":"2015","unstructured":"Hall J, Trent S, Thomas KL, O\u2019Donovan MC, Owen MJ. Genetic risk for schizophrenia: convergence on synaptic pathways involved in plasticity. Biol Psychiatry. 2015;77:52\u20138.","journal-title":"Biol Psychiatry"},{"key":"3654_CR10","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41586-022-04556-w","volume":"604","author":"T Singh","year":"2022","unstructured":"Singh T, Poterba T, Curtis D, Akil H, Al Eissa M, Barchas JD, et al. Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature. 2022;604:509\u201316.","journal-title":"Nature"},{"key":"3654_CR11","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.schres.2021.10.012","volume":"242","author":"MJ Owen","year":"2022","unstructured":"Owen MJ, Legge SE. The nature of schizophrenia: As broad as it is long. Schizophr Res. 2022;242:109\u201312.","journal-title":"Schizophr Res"},{"key":"3654_CR12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.schres.2013.05.028","volume":"150","author":"R Tandon","year":"2013","unstructured":"Tandon R, Gaebel W, Barch DM, Bustillo J, Gur RE, Heckers S, et al. Definition and description of schizophrenia in the DSM-5. Schizophr Res. 2013;150:3\u201310.","journal-title":"Schizophr Res"},{"key":"3654_CR13","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1002\/wps.20624","volume":"18","author":"MF Green","year":"2019","unstructured":"Green MF, Horan WP, Lee J. Nonsocial and social cognition in schizophrenia: current evidence and future directions. World Psychiatry. 2019;18:146\u201361.","journal-title":"World Psychiatry"},{"key":"3654_CR14","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.biopsych.2018.04.023","volume":"84","author":"TGM van Erp","year":"2018","unstructured":"van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, et al. Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA) Consortium. Biol Psychiatry. 2018;84:644\u201354.","journal-title":"Biol Psychiatry"},{"key":"3654_CR15","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/mp.2015.118","volume":"21","author":"TG van Erp","year":"2016","unstructured":"van Erp TG, Hibar DP, Rasmussen JM, Glahn DC, Pearlson GD, Andreassen OA, et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry. 2016;21:585.","journal-title":"Mol Psychiatry"},{"key":"3654_CR16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1093\/schbul\/sbad087","volume":"50","author":"H Jameei","year":"2024","unstructured":"Jameei H, Rakesh D, Zalesky A, Cairns MJ, Reay WR, Wray NR, et al. Linking polygenic risk of schizophrenia to variation in magnetic resonance imaging brain measures: a comprehensive systematic review. Schizophr Bull. 2024;50:32\u201346.","journal-title":"Schizophr Bull"},{"key":"3654_CR17","doi-asserted-by":"crossref","unstructured":"Murray RM, Alameda L, Dima A, Oliver D Beyond Kraepelin: An Aetiological Approach to the Typology and Treatment of Psychosis. In: Ikkos G, Becker T (eds). Psychiatry after Kraepelin: Ambition Images Practices 1926-2026. Cham: Springer Nature Switzerland, 2026, pp 417-48.","DOI":"10.1007\/978-3-032-09475-9_25"},{"key":"3654_CR18","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1038\/s41588-024-01771-1","volume":"56","author":"O Frei","year":"2024","unstructured":"Frei O, Hindley G, Shadrin AA, van der Meer D, Akdeniz BC, Hagen E, et al. Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets. Nat Genet. 2024;56:1310\u20138.","journal-title":"Nat Genet"},{"key":"3654_CR19","unstructured":"Weinberger DR The pathogenesis of schizophrenia: a neurodevelopmental theory. In: Nasrallah HA, Weinberger DR (eds). The Neurology of schizophrenia. Amsterdam: Elsevier, 1986, pp 387-405."},{"key":"3654_CR20","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1001\/archpsyc.1987.01800190080012","volume":"44","author":"DR Weinberger","year":"1987","unstructured":"Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987;44:660\u20139.","journal-title":"Arch Gen Psychiatry"},{"key":"3654_CR21","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1136\/bmj.295.6600.681","volume":"295","author":"RM Murray","year":"1987","unstructured":"Murray RM, Lewis SW. Is schizophrenia a neurodevelopmental disorder? Br Med J (Clin Res Ed). 1987;295:681\u20132.","journal-title":"Br Med J (Clin Res Ed)"},{"key":"3654_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1567-1","volume":"19","author":"HE O\u2019Brien","year":"2018","unstructured":"O\u2019Brien HE, Hannon E, Hill MJ, Toste CC, Robertson MJ, Morgan JE, et al. Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders. Genome Biol. 2018;19:194.","journal-title":"Genome Biol"},{"key":"3654_CR23","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.biopsych.2021.10.018","volume":"91","author":"J Hall","year":"2022","unstructured":"Hall J, Bray NJ. Schizophrenia genomics: convergence on synaptic development, adult synaptic plasticity, or both? Biol Psychiatry. 2022;91:709\u201317.","journal-title":"Biol Psychiatry"},{"key":"3654_CR24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.biopsych.2022.06.033","volume":"93","author":"D Cameron","year":"2023","unstructured":"Cameron D, Mi D, Vinh NN, Webber C, Li M, Mar\u00edn O, et al. Single-nuclei RNA sequencing of 5 regions of the human prenatal brain implicates developing neuron populations in genetic risk for schizophrenia. Biol Psychiatry. 2023;93:157\u201366.","journal-title":"Biol Psychiatry"},{"key":"3654_CR25","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1002\/wps.20440","volume":"16","author":"MJ Owen","year":"2017","unstructured":"Owen MJ, O\u2019Donovan MC. Schizophrenia and the neurodevelopmental continuum:evidence from genomics. World Psychiatry. 2017;16:227\u201335.","journal-title":"World Psychiatry"},{"key":"3654_CR26","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/S0140-6736(15)01121-6","volume":"388","author":"MJ Owen","year":"2016","unstructured":"Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016;388:86\u201397.","journal-title":"Lancet"},{"key":"3654_CR27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1192\/bjp.bp.109.073429","volume":"196","author":"N Craddock","year":"2010","unstructured":"Craddock N, Owen MJ. The Kraepelinian dichotomy - going, going\u2026 but still not gone. Br J Psychiatry. 2010;196:92\u201395.","journal-title":"Br J Psychiatry"},{"key":"3654_CR28","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.neuron.2014.10.028","volume":"84","author":"MJ Owen","year":"2014","unstructured":"Owen MJ. New approaches to psychiatric diagnostic classification. Neuron. 2014;84:564\u201371.","journal-title":"Neuron"},{"key":"3654_CR29","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1093\/ije\/dyw067","volume":"45","author":"AM Lilienfeld","year":"2016","unstructured":"Lilienfeld AM, Pasamanick B, Rogers M. Relationship between pregnancy experience and the development of certain neuropsychiatric disorders in childhood. Int J Epidemiol. 2016;45:311\u20136.","journal-title":"Int J Epidemiol"},{"key":"3654_CR30","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1503\/jpn.170076","volume":"43","author":"AJ Lynham","year":"2018","unstructured":"Lynham AJ, Hubbard L, Tansey KE, Hamshere ML, Legge SE, Owen MJ, et al. Examining cognition across the bipolar\/schizophrenia diagnostic spectrum. J Psychiatry Neurosci. 2018;43:245\u201353.","journal-title":"J Psychiatry Neurosci"},{"key":"3654_CR31","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/pcn.13337","volume":"76","author":"EJ Cheon","year":"2022","unstructured":"Cheon EJ, Bearden CE, Sun D, Ching CRK, Andreassen OA, Schmaal L, et al. Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings. Psychiatry Clin Neurosci. 2022;76:140\u201361.","journal-title":"Psychiatry Clin Neurosci"},{"key":"3654_CR32","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1001\/jamapsychiatry.2016.0053","volume":"73","author":"KS Kendler","year":"2016","unstructured":"Kendler KS, Ohlsson H, Mezuk B, Sundquist JO, Sundquist K. Observed cognitive performance and deviation from familial cognitive aptitude at age 16 years and ages 18 to 20 years and risk for schizophrenia and bipolar illness in a Swedish national sample. JAMA Psychiatry. 2016;73:465\u201371.","journal-title":"JAMA Psychiatry"},{"key":"3654_CR33","doi-asserted-by":"publisher","first-page":"28","DOI":"10.61373\/gp024i.0040","volume":"1","author":"MJ Owen","year":"2024","unstructured":"Owen MJ, O\u2019Donovan MC. The genetics of cognition in schizophrenia. Genomic Psychiatry. 2024;1:28\u201335.","journal-title":"Genomic Psychiatry"},{"key":"3654_CR34","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/mp.2017.78","volume":"23","author":"KS Kendler","year":"2018","unstructured":"Kendler KS, Ohlsson H, Keefe RSE, Sundquist K, Sundquist J. The joint impact of cognitive performance in adolescence and familial cognitive aptitude on risk for major psychiatric disorders: a delineation of four potential pathways to illness. Mol Psychiatry. 2018;23:1076\u201383.","journal-title":"Mol Psychiatry"},{"key":"3654_CR35","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1038\/nm.4196","volume":"22","author":"MC O\u2019Donovan","year":"2016","unstructured":"O\u2019Donovan MC, Owen MJ. The implications of the shared genetics of psychiatric disorders. Nat Med. 2016;22:1214\u20139.","journal-title":"Nat Med"},{"key":"3654_CR36","doi-asserted-by":"publisher","first-page":"eaap8757","DOI":"10.1126\/science.aap8757","volume":"360","author":"B Consortium","year":"2018","unstructured":"Consortium B, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, et al. Analysis of shared heritability in common disorders of the brain. Science. 2018;360:eaap8757.","journal-title":"Science"},{"key":"3654_CR37","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/s41588-022-01057-4","volume":"54","author":"AD Grotzinger","year":"2022","unstructured":"Grotzinger AD, Mallard TT, Akingbuwa WA, Ip HF, Adams MJ, Lewis CM, et al. Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis. Nat Genet. 2022;54:548\u201359.","journal-title":"Nat Genet"},{"key":"3654_CR38","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/mp.2011.11","volume":"17","author":"AL Richards","year":"2012","unstructured":"Richards AL, Jones L, Moskvina V, Kirov G, Gejman PV, Levinson DF, et al. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain. Mol Psychiatry. 2012;17:193\u2013201.","journal-title":"Mol Psychiatry"},{"key":"3654_CR39","doi-asserted-by":"publisher","first-page":"eaat8464","DOI":"10.1126\/science.aat8464","volume":"362","author":"D Wang","year":"2018","unstructured":"Wang D, Liu S, Warrell J, Won H, Shi X, Navarro FCP, et al. Comprehensive functional genomic resource and integrative model for the human brain. Science. 2018;362:eaat8464.","journal-title":"Science"},{"key":"3654_CR40","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1038\/s41593-022-01128-z","volume":"25","author":"J Bryois","year":"2022","unstructured":"Bryois J, Calini D, Macnair W, Foo L, Urich E, Ortmann W, et al. Cell-type-specific cis-eQTLs in eight human brain cell types identify novel risk genes for psychiatric and neurological disorders. Nat Neurosci. 2022;25:1104\u201312.","journal-title":"Nat Neurosci"},{"key":"3654_CR41","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.neuron.2015.04.022","volume":"86","author":"AJ Pocklington","year":"2015","unstructured":"Pocklington AJ, Rees E, Walters JT, Han J, Kavanagh DH, Chambert KD, et al. Novel findings from CNVs implicate inhibitory and excitatory signaling complexes in schizophrenia. Neuron. 2015;86:1203\u201314.","journal-title":"Neuron"},{"key":"3654_CR42","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1038\/s41380-023-02043-w","volume":"28","author":"OD Howes","year":"2023","unstructured":"Howes OD, Onwordi EC. The synaptic hypothesis of schizophrenia version III: a master mechanism. Mol Psychiatry. 2023;28:1843\u201356.","journal-title":"Mol Psychiatry"},{"key":"3654_CR43","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1136\/bmj.330.7484.158","volume":"330","author":"MJ Owen","year":"2005","unstructured":"Owen MJ, O\u2019Donovan MC, Harrison PJ. Schizophrenia: a genetic disorder of the synapse? Bmj. 2005;330:158\u20139.","journal-title":"Bmj"},{"key":"3654_CR44","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.schres.2016.07.014","volume":"176","author":"K Friston","year":"2016","unstructured":"Friston K, Brown HR, Siemerkus J, Stephan KE. The dysconnection hypothesis (2016). Schizophr Res. 2016;176:83\u201394.","journal-title":"Schizophr Res"},{"key":"3654_CR45","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.neuron.2021.10.035","volume":"110","author":"G Panagiotakos","year":"2022","unstructured":"Panagiotakos G, Pasca SP. A matter of space and time: Emerging roles of disease-associated proteins in neural development. Neuron. 2022;110:195\u2013208.","journal-title":"Neuron"},{"key":"3654_CR46","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1038\/s41380-023-01949-9","volume":"28","author":"RA McCutcheon","year":"2023","unstructured":"McCutcheon RA, Keefe RSE, McGuire PK. Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment. Mol Psychiatry. 2023;28:1902\u201318.","journal-title":"Mol Psychiatry"},{"key":"3654_CR47","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.schres.2011.06.017","volume":"132","author":"GM Khandaker","year":"2011","unstructured":"Khandaker GM, Barnett JH, White IR, Jones PB. A quantitative meta-analysis of population-based studies of premorbid intelligence and schizophrenia. Schizophr Res. 2011;132:220\u20137.","journal-title":"Schizophr Res"},{"key":"3654_CR48","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1176\/appi.ajp.2014.14040516","volume":"172","author":"KS Kendler","year":"2015","unstructured":"Kendler KS, Ohlsson H, Sundquist J, Sundquist K. IQ and schizophrenia in a Swedish national sample: their causal relationship and the interaction of IQ with genetic risk. Am J Psychiatry. 2015;172:259\u201365.","journal-title":"Am J Psychiatry"},{"key":"3654_CR49","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.neubiorev.2021.11.034","volume":"132","author":"M Khalil","year":"2022","unstructured":"Khalil M, Hollander P, Raucher-Ch\u00e9n\u00e9 D, Lepage M, Lavigne KM. Structural brain correlates of cognitive function in schizophrenia: A meta-analysis. Neurosci Biobehav Rev. 2022;132:37\u201349.","journal-title":"Neurosci Biobehav Rev"},{"key":"3654_CR50","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1177\/0963721410377601","volume":"19","author":"KH Karlsgodt","year":"2010","unstructured":"Karlsgodt KH, Sun D, Cannon TD. Structural and functional brain abnormalities in schizophrenia. Curr Dir Psychol Sci. 2010;19:226\u201331.","journal-title":"Curr Dir Psychol Sci"},{"key":"3654_CR51","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.comppsych.2018.11.014","volume":"88","author":"C van der Merwe","year":"2019","unstructured":"van der Merwe C, Passchier R, Mufford M, Ramesar R, Dalvie S, Stein DJ. Polygenic risk for schizophrenia and associated brain structural changes: A systematic review. Compr Psychiatry. 2019;88:77\u201382.","journal-title":"Compr Psychiatry"},{"key":"3654_CR52","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.jad.2022.05.007","volume":"310","author":"G Cattarinussi","year":"2022","unstructured":"Cattarinussi G, Delvecchio G, Sambataro F, Brambilla P. The effect of polygenic risk scores for major depressive disorder, bipolar disorder and schizophrenia on morphological brain measures: a systematic review of the evidence. J Affect Disord. 2022;310:213\u201322.","journal-title":"J Affect Disord"},{"key":"3654_CR53","doi-asserted-by":"publisher","first-page":"7709","DOI":"10.1038\/s41380-021-01260-5","volume":"26","author":"EM Stauffer","year":"2021","unstructured":"Stauffer EM, Bethlehem RAI, Warrier V, Murray GK, Romero-Garcia R, Seidlitz J, et al. Grey and white matter microstructure is associated with polygenic risk for schizophrenia. Mol Psychiatry. 2021;26:7709\u201318.","journal-title":"Mol Psychiatry"},{"key":"3654_CR54","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.biopsych.2020.11.025","volume":"90","author":"L Hubbard","year":"2021","unstructured":"Hubbard L, Rees E, Morris DW, Lynham AJ, Richards AL, Pardi\u00f1as AF, et al. Rare copy number variants are associated with poorer cognition in schizophrenia. Biol Psychiatry. 2021;90:28\u201334.","journal-title":"Biol Psychiatry"},{"key":"3654_CR55","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/sj.mp.4001642","volume":"10","author":"JL Rapoport","year":"2005","unstructured":"Rapoport JL, Addington AM, Frangou S, Psych MR. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry. 2005;10:434\u201349.","journal-title":"Mol Psychiatry"},{"key":"3654_CR56","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1176\/appi.ajp.20220235","volume":"179","author":"KJ Brennand","year":"2022","unstructured":"Brennand KJ. Using stem cell models to explore the genetics underlying psychiatric disorders: linking risk variants, genes, and biology in brain disease. Am J Psychiatry. 2022;179:322\u20138.","journal-title":"Am J Psychiatry"},{"key":"3654_CR57","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/sj.mp.4002068","volume":"12","author":"JT Walters","year":"2007","unstructured":"Walters JT, Owen MJ. Endophenotypes in psychiatric genetics. Mol Psychiatry. 2007;12:886\u201390.","journal-title":"Mol Psychiatry"},{"key":"3654_CR58","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1038\/mp.2010.8","volume":"15","author":"KS Kendler","year":"2010","unstructured":"Kendler KS, Neale MC. Endophenotype: a conceptual analysis. Mol Psychiatry. 2010;15:789\u201397.","journal-title":"Mol Psychiatry"},{"key":"3654_CR59","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1126\/science.adq1456","volume":"386","author":"EA Maury","year":"2024","unstructured":"Maury EA, Jones A, Seplyarskiy V, Nguyen TTL, Rosenbluh C, Bae T, et al. Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes. Science. 2024;386:217\u201324.","journal-title":"Science"},{"key":"3654_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27601-0","volume":"13","author":"B Sanders","year":"2022","unstructured":"Sanders B, D\u2019Andrea D, Collins MO, Rees E, Steward TGJ, Zhu Y, et al. Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants. Nat Commun. 2022;13:27.","journal-title":"Nat Commun"},{"key":"3654_CR61","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-019-1091-3","volume":"21","author":"SA Stilo","year":"2019","unstructured":"Stilo SA, Murray RM. Non-genetic factors in schizophrenia. Curr Psychiatry Rep. 2019;21:100.","journal-title":"Curr Psychiatry Rep"},{"key":"3654_CR62","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/978-3-031-69491-2_23","volume":"40","author":"BA Clementz","year":"2024","unstructured":"Clementz BA, Assaf M, Sweeney JA, Gershon ES, Keedy SK, Hill SK, et al. Categorical and dimensional approaches for psychiatric classification and treatment targeting: considerations from psychosis biotypes. Adv Neurobiol. 2024;40:685\u2013723.","journal-title":"Adv Neurobiol"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03654-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03654-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03654-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:38:08Z","timestamp":1789112288000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03654-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":62,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["3654"],"URL":"https:\/\/doi.org\/10.1038\/s41380-026-03654-9","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"assertion":[{"value":"5 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MO and MO\u2019D have received research funding from Akrivia Health outside of the scope of the present work. Akrivia played no part in the conception or writing of this article, the conclusions expressed or the decision to submit.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}