{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:31:55Z","timestamp":1792189915292,"version":"4.4.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["334525"],"award-info":[{"award-number":["334525"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["336823"],"award-info":[{"award-number":["336823"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sigrid Juselius Foundation Business Finland"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes compared to healthy individuals. Microglia from affected twins had also reduced response to interleukin 1 beta (IL1\u03b2) treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent Gene Ontology (GO) terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation.<\/jats:p>","DOI":"10.1038\/s41380-024-02529-1","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T05:02:41Z","timestamp":1711083761000},"page":"2622-2633","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Genetic contribution to microglial activation in schizophrenia"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1646-9992","authenticated-orcid":false,"given":"Marja","family":"Koskuvi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8880-9909","authenticated-orcid":false,"given":"Elina","family":"P\u00f6rsti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristen","family":"Hewitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"R\u00e4s\u00e4nen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chieh","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalevi","family":"Trontti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5368-6788","authenticated-orcid":false,"given":"Amanda","family":"McQuade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shringaa","family":"Kalyanaraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Ojansuu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Vaurio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-3154","authenticated-orcid":false,"given":"Tyrone D.","family":"Cannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jouko","family":"L\u00f6nnqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-4905","authenticated-orcid":false,"given":"Sebastian","family":"Therman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-0990","authenticated-orcid":false,"given":"Jaana","family":"Suvisaari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-2455","authenticated-orcid":false,"given":"Jaakko","family":"Kaprio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-7157","authenticated-orcid":false,"given":"Mathew","family":"Blurton-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5990-7892","authenticated-orcid":false,"given":"Iiris","family":"Hovatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-145X","authenticated-orcid":false,"given":"Markku","family":"L\u00e4hteenvuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisia","family":"Rolova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-9414","authenticated-orcid":false,"given":"\u0160\u00e1rka","family":"Lehtonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Tiihonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6559-1153","authenticated-orcid":false,"given":"Jari","family":"Koistinaho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"2529_CR1","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3389\/fpsyt.2020.00160","volume":"11","author":"G Fond","year":"2020","unstructured":"Fond G, Lan\u00e7on C, Korchia T, Auquier P, Boyer L. The role of inflammation in the treatment of schizophrenia. Front Psychiatry. 2020;11:160.","journal-title":"Front Psychiatry"},{"key":"2529_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01607-0","volume":"11","author":"CE Murphy","year":"2021","unstructured":"Murphy CE, Walker AK, Weickert CS. Neuroinflammation in schizophrenia: the role of nuclear factor kappa B. Transl Psychiatry. 2021;11:528.","journal-title":"Transl Psychiatry"},{"key":"2529_CR3","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.3390\/genes12121850","volume":"12","author":"MH Wahbeh","year":"2021","unstructured":"Wahbeh MH, Avramopoulos D. Gene-environment interactions in schizophrenia: a literature review. Genes. 2021;12:1850.","journal-title":"Genes"},{"key":"2529_CR4","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1440-1819.2009.01945.x","volume":"63","author":"A Monji","year":"2009","unstructured":"Monji A, Kato T, Kanba S. Cytokines and schizophrenia: microglia hypothesis of schizophrenia: cytokines and schizophrenia. Psychiatry Clin Neurosci. 2009;63:257\u201365.","journal-title":"Psychiatry Clin Neurosci"},{"key":"2529_CR5","doi-asserted-by":"publisher","first-page":"e13003","DOI":"10.1111\/bpa.13003","volume":"32","author":"R Gober","year":"2022","unstructured":"Gober R, Ardalan M, Shiadeh SMJ, Duque L, Garamszegi SP, Ascona M, et al. Microglia activation in postmortem brains with schizophrenia demonstrates distinct morphological changes between brain regions. Brain Pathol. 2022;32:e13003.","journal-title":"Brain Pathol"},{"key":"2529_CR6","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/mp.2012.110","volume":"18","author":"SG Fillman","year":"2013","unstructured":"Fillman SG, Cloonan N, Catts VS, Miller LC, Wong J, McCrossin T, et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry. 2013;18:206\u201314.","journal-title":"Mol Psychiatry"},{"key":"2529_CR7","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00401-006-0090-8","volume":"112","author":"J Steiner","year":"2006","unstructured":"Steiner J, Mawrin C, Ziegeler A, Bielau H, Ullrich O, Bernstein HG, et al. Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. Acta Neuropathol. 2006;112:305\u201316.","journal-title":"Acta Neuropathol"},{"key":"2529_CR8","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1038\/mp.2016.3","volume":"21","author":"DR Goldsmith","year":"2016","unstructured":"Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016;21:1696\u2013709.","journal-title":"Mol Psychiatry"},{"key":"2529_CR9","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/nature13595","volume":"511","author":"Schizophrenia Working Group of the Psychiatric Genomics Consortium.","year":"2014","unstructured":"Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421\u20137.","journal-title":"Nature"},{"key":"2529_CR10","doi-asserted-by":"publisher","first-page":"479","DOI":"10.4172\/2155-9899.1000479","volume":"07","author":"R Mokhtari","year":"2016","unstructured":"Mokhtari R, Lachman HM. The major histocompatibility complex (MHC) in schizophrenia: a review. J Clin Cell Immunol. 2016;07:479.","journal-title":"J Clin Cell Immunol"},{"key":"2529_CR11","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/s42003-023-04852-9","volume":"6","author":"R Breitmeyer","year":"2023","unstructured":"Breitmeyer R, Vogel S, Heider J, Hartmann SM, W\u00fcst R, Keller AL, et al. Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction. Commun Biol. 2023;6:472.","journal-title":"Commun Biol"},{"key":"2529_CR12","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41593-018-0334-7","volume":"22","author":"CM Sellgren","year":"2019","unstructured":"Sellgren CM, Gracias J, Watmuff B, Biag JD, Thanos JM, Whittredge PB, et al. Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. Nat Neurosci. 2019;22:374\u201385.","journal-title":"Nat Neurosci"},{"key":"2529_CR13","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1523\/JNEUROSCI.21-08-02580.2001","volume":"21","author":"T Tikka","year":"2001","unstructured":"Tikka T, Fiebich BL, Goldsteins G, Kein\u00e4nen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001;21:2580\u20138.","journal-title":"J Neurosci"},{"key":"2529_CR14","doi-asserted-by":"publisher","first-page":"13496","DOI":"10.1073\/pnas.96.23.13496","volume":"96","author":"J Yrj\u00e4nheikki","year":"1999","unstructured":"Yrj\u00e4nheikki J, Tikka T, Kein\u00e4nen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci. 1999;96:13496\u2013500.","journal-title":"Proc Natl Acad Sci"},{"key":"2529_CR15","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.jnutbio.2016.10.004","volume":"39","author":"JC Zhang","year":"2017","unstructured":"Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, et al. Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation. J Nutr Biochem. 2017;39:134\u201344.","journal-title":"J Nutr Biochem"},{"key":"2529_CR16","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/s41401-021-00727-z","volume":"43","author":"R Tang","year":"2022","unstructured":"Tang R, Cao QQ, Hu SW, He LJ, Du PF, Chen G, et al. Sulforaphane activates anti-inflammatory microglia, modulating stress resilience associated with BDNF transcription. Acta Pharm Sin. 2022;43:829\u201339.","journal-title":"Acta Pharm Sin"},{"key":"2529_CR17","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.pnpbp.2017.04.012","volume":"81","author":"S Jeon","year":"2018","unstructured":"Jeon S, Kim SH, Shin SY, Lee YH. Clozapine reduces Toll-like receptor 4\/NF-\u03baB-mediated inflammatory responses through inhibition of calcium\/calmodulin-dependent Akt activation in microglia. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:477\u201387.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2529_CR18","doi-asserted-by":"publisher","first-page":"e525","DOI":"10.1038\/cddis.2013.54","volume":"4","author":"K Kobayashi","year":"2013","unstructured":"Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K, et al. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis. 2013;4:e525.","journal-title":"Cell Death Dis"},{"key":"2529_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11797-3","volume":"10","author":"J Tiihonen","year":"2019","unstructured":"Tiihonen J, Koskuvi M, Storvik M, Hy\u00f6tyl\u00e4inen I, Gao Y, Puttonen KA, et al. Sex-specific transcriptional and proteomic signatures in schizophrenia. Nat Commun. 2019;10:3933.","journal-title":"Nat Commun"},{"key":"2529_CR20","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13024-018-0297-x","volume":"13","author":"A McQuade","year":"2018","unstructured":"McQuade A, Coburn M, Tu CH, Hasselmann J, Davtyan H, Blurton-Jones M. Development and validation of a simplified method to generate human microglia from pluripotent stem cells. Mol Neurodegener. 2018;13:67.","journal-title":"Mol Neurodegener"},{"key":"2529_CR21","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1002\/glia.23962","volume":"69","author":"GJLJ Snijders","year":"2021","unstructured":"Snijders GJLJ, Zuiden W, Sneeboer MAM, Berdenis van Berlekom A, Geest AT, Schnieder T, et al. A loss of mature microglial markers without immune activation in schizophrenia. Glia. 2021;69:1251\u201367.","journal-title":"Glia"},{"key":"2529_CR22","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fncel.2020.00198","volume":"14","author":"AM Jurga","year":"2020","unstructured":"Jurga AM, Paleczna M, Kuter KZ. Overview of general and discriminating markers of differential microglia phenotypes. Front Cell Neurosci. 2020;14:198.","journal-title":"Front Cell Neurosci"},{"key":"2529_CR23","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1038\/mp.2016.90","volume":"21","author":"MO Tr\u00e9panier","year":"2016","unstructured":"Tr\u00e9panier MO, Hopperton KE, Mizrahi R, Mechawar N, Bazinet RP. Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review. Mol Psychiatry. 2016;21:1009\u201326.","journal-title":"Mol Psychiatry"},{"key":"2529_CR24","doi-asserted-by":"publisher","first-page":"e5","DOI":"10.1016\/j.biopsych.2020.05.028","volume":"89","author":"P Plav\u00e9n-Sigray","year":"2021","unstructured":"Plav\u00e9n-Sigray P, Matheson GJ, Coughlin JM, Hafizi S, Laurikainen H, Ottoy J, et al. Meta-analysis of the glial marker TSPO in psychosis revisited: reconciling inconclusive findings of patient\u2013control differences. Biol Psychiatry. 2021;89:e5\u20138.","journal-title":"Biol Psychiatry"},{"key":"2529_CR25","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1177\/09680519030090030601","volume":"9","author":"DM Underhill","year":"2003","unstructured":"Underhill DM. Macrophage recognition of zymosan particles. J Endotoxin Res. 2003;9:176\u201380.","journal-title":"J Endotoxin Res"},{"key":"2529_CR26","doi-asserted-by":"publisher","first-page":"123","DOI":"10.2174\/138945008783502430","volume":"9","author":"J Schorey","year":"2008","unstructured":"Schorey J, Lawrence C. The pattern recognition receptor dectin-1: from fungi to mycobacteria. Curr Drug Targets. 2008;9:123\u20139.","journal-title":"Curr Drug Targets"},{"key":"2529_CR27","doi-asserted-by":"publisher","first-page":"658","DOI":"10.3390\/brainsci11050658","volume":"11","author":"DR P\u00e9rez-Rodr\u00edguez","year":"2021","unstructured":"P\u00e9rez-Rodr\u00edguez DR, Blanco-Luquin I, Mendioroz M. The participation of microglia in neurogenesis: a review. Brain Sci. 2021;11:658.","journal-title":"Brain Sci"},{"key":"2529_CR28","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","volume":"155","author":"CN Parkhurst","year":"2013","unstructured":"Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR, Lafaille JJ, et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 2013;155:1596\u2013609.","journal-title":"Cell"},{"key":"2529_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.662407","volume":"12","author":"RR Nieto","year":"2021","unstructured":"Nieto RR, Carrasco A, Corral S, Castillo R, Gaspar PA, Bustamante ML, et al. BDNF as a biomarker of cognition in schizophrenia\/psychosis: an updated review. Front Psychiatry. 2021;12:662407.","journal-title":"Front Psychiatry"},{"key":"2529_CR30","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3390\/jcm9020456","volume":"9","author":"M Duarte Azevedo","year":"2020","unstructured":"Duarte Azevedo M, Sander S, Tenenbaum L. GDNF, a neuron-derived factor upregulated in glial cells during disease. J Clin Med. 2020;9:456.","journal-title":"J Clin Med"},{"key":"2529_CR31","doi-asserted-by":"publisher","first-page":"633","DOI":"10.4252\/wjsc.v12.i7.633","volume":"12","author":"F Yang","year":"2020","unstructured":"Yang F, Li WB, Qu YW, Gao JX, Tang YS, Wang DJ, et al. Bone marrow mesenchymal stem cells induce M2 microglia polarization through PDGF-AA\/MANF signaling. World J Stem Cells. 2020;12:633\u201358.","journal-title":"World J Stem Cells"},{"key":"2529_CR32","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1136\/svn-2016-000012","volume":"1","author":"H Liu","year":"2016","unstructured":"Liu H, Leak RK, Hu X. Neurotransmitter receptors on microglia. Stroke Vasc Neurol. 2016;1:52\u20138.","journal-title":"Stroke Vasc Neurol"},{"key":"2529_CR33","first-page":"49","volume":"7","author":"M Domercq","year":"2013","unstructured":"Domercq M, V\u00e1zquez-Villoldo N, Matute C. Neurotransmitter signaling in the pathophysiology of microglia. Front Cell Neurosci. 2013;7:49.","journal-title":"Front Cell Neurosci"},{"key":"2529_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110128","volume":"37","author":"F Logiacco","year":"2021","unstructured":"Logiacco F, Xia P, Georgiev SV, Franconi C, Chang YJ, Ugursu B, et al. Microglia sense neuronal activity via GABA in the early postnatal hippocampus. Cell Rep. 2021;37:110128.","journal-title":"Cell Rep"},{"key":"2529_CR35","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.schres.2021.05.011","volume":"232","author":"J Tiihonen","year":"2021","unstructured":"Tiihonen J, Koskuvi M, L\u00e4hteenvuo M, Trontti K, Ojansuu I, Vaurio O, et al. Molecular signaling pathways underlying schizophrenia. Schizophr Res. 2021;232:33\u201341.","journal-title":"Schizophr Res"},{"key":"2529_CR36","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1002\/glia.24131","volume":"70","author":"M Koskuvi","year":"2022","unstructured":"Koskuvi M, Lehtonen \u0160, Trontti K, Keuters M, Wu Y, Koivisto H, et al. Contribution of astrocytes to familial risk and clinical manifestation of schizophrenia. Glia. 2022;70:650\u201360.","journal-title":"Glia"},{"key":"2529_CR37","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/nature08192","volume":"460","author":"J Shi","year":"2009","unstructured":"Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe\u2019er I, et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009;460:753\u20137.","journal-title":"Nature"},{"key":"2529_CR38","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.phrs.2018.01.014","volume":"133","author":"S Qin","year":"2018","unstructured":"Qin S, Yang C, Huang W, Du S, Mai H, Xiao J, et al. Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK\/NF-\u03baB signaling pathways in LPS-activated BV-2 microglia. Pharm Res. 2018;133:218\u201335.","journal-title":"Pharm Res"},{"key":"2529_CR39","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jnutbio.2019.01.019","volume":"67","author":"Y Wu","year":"2019","unstructured":"Wu Y, Gao M, Wu J, Hu P, Xu X, Zhang Y, et al. Sulforaphane triggers a functional elongation of microglial process via the Akt signal. J Nutr Biochem. 2019;67:51\u201362.","journal-title":"J Nutr Biochem"},{"key":"2529_CR40","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-15","volume":"5","author":"CJ Henry","year":"2008","unstructured":"Henry CJ, Huang Y, Wynne A, Hanke M, Himler J, Bailey MT, et al. Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation. 2008;5:15.","journal-title":"J Neuroinflammation"},{"key":"2529_CR41","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/cells8020194","volume":"8","author":"L Subedi","year":"2019","unstructured":"Subedi L, Lee J, Yumnam S, Ji E, Kim S. Anti-inflammatory effect of sulforaphane on LPS-activated microglia potentially through JNK\/AP-1\/NF-\u03baB inhibition and Nrf2\/HO-1 activation. Cells 2019;8:194.","journal-title":"Cells"},{"key":"2529_CR42","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.neuron.2019.07.002","volume":"103","author":"J Hasselmann","year":"2019","unstructured":"Hasselmann J, Coburn MA, England W, Figueroa Velez DX, Kiani Shabestari S, Tu CH, et al. Development of a chimeric model to study and manipulate human microglia in vivo. Neuron. 2019;103:1016\u201333.e10.","journal-title":"Neuron"},{"key":"2529_CR43","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.bbi.2013.01.087","volume":"32","author":"ML Sinkus","year":"2013","unstructured":"Sinkus ML, Adams CE, Logel J, Freedman R, Leonard S. Expression of immune genes on chromosome 6p21.3\u201322.1 in schizophrenia. Brain Behav Immun. 2013;32:51\u201362.","journal-title":"Brain Behav Immun"},{"key":"2529_CR44","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.neuropharm.2014.10.028","volume":"96","author":"DM Norden","year":"2015","unstructured":"Norden DM, Muccigrosso MM, Godbout JP. Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease. Neuropharmacology. 2015;96:29\u201341.","journal-title":"Neuropharmacology"},{"key":"2529_CR45","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbw088","volume":"43","author":"D Inta","year":"2016","unstructured":"Inta D, Lang UE, Borgwardt S, Meyer-Lindenberg A, Gass P. Microglia activation and schizophrenia: lessons from the effects of minocycline on postnatal neurogenesis, neuronal survival and synaptic pruning. Schizophr Bull. 2016;43:sbw088.","journal-title":"Schizophr Bull"},{"key":"2529_CR46","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.3389\/fimmu.2017.01905","volume":"8","author":"STT Schetters","year":"2018","unstructured":"Schetters STT, Gomez-Nicola D, Garcia-Vallejo JJ, Van Kooyk Y. Neuroinflammation: microglia and T cells get ready to tango. Front Immunol. 2018;8:1905.","journal-title":"Front Immunol"},{"key":"2529_CR47","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nri3818","volume":"15","author":"PA Roche","year":"2015","unstructured":"Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol. 2015;15:203\u201316.","journal-title":"Nat Rev Immunol"},{"key":"2529_CR48","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.bbi.2020.04.021","volume":"88","author":"K Schlaaff","year":"2020","unstructured":"Schlaaff K, Dobrowolny H, Frodl T, Mawrin C, Gos T, Steiner J, et al. Increased densities of T and B lymphocytes indicate neuroinflammation in subgroups of schizophrenia and mood disorder patients. Brain Behav Immun. 2020;88:497\u2013506.","journal-title":"Brain Behav Immun"},{"key":"2529_CR49","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.bbi.2012.08.005","volume":"26","author":"S Busse","year":"2012","unstructured":"Busse S, Busse M, Schiltz K, Bielau H, Gos T, Brisch R, et al. Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations? Brain Behav Immun. 2012;26:1273\u20139.","journal-title":"Brain Behav Immun"},{"key":"2529_CR50","doi-asserted-by":"publisher","first-page":"7105","DOI":"10.1038\/s41380-021-01225-8","volume":"26","author":"CE Murphy","year":"2021","unstructured":"Murphy CE, Weickert CS. A new suspect in the unsolved case of neuroinflammation in schizophrenia. Mol Psychiatry. 2021;26:7105\u20136.","journal-title":"Mol Psychiatry"},{"key":"2529_CR51","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.neubiorev.2021.03.004","volume":"125","author":"F Corsi-Zuelli","year":"2021","unstructured":"Corsi-Zuelli F, Deakin B. Impaired regulatory T cell control of astroglial overdrive and microglial pruning in schizophrenia. Neurosci Biobehav Rev. 2021;125:637\u201353.","journal-title":"Neurosci Biobehav Rev"},{"key":"2529_CR52","doi-asserted-by":"publisher","first-page":"eaat8127","DOI":"10.1126\/science.aat8127","volume":"362","author":"MJ Gandal","year":"2018","unstructured":"Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science 2018;362:eaat8127.","journal-title":"Science"},{"key":"2529_CR53","doi-asserted-by":"publisher","first-page":"2472","DOI":"10.1038\/s41423-021-00751-3","volume":"18","author":"JD Crapser","year":"2021","unstructured":"Crapser JD, Arreola MA, Tsourmas KI, Green KN. Microglia as hackers of the matrix: sculpting synapses and the extracellular space. Cell Mol Immunol. 2021;18:2472\u201388.","journal-title":"Cell Mol Immunol"},{"key":"2529_CR54","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.3390\/cells10081862","volume":"10","author":"L Strackeljan","year":"2021","unstructured":"Strackeljan L, Baczynska E, Cangalaya C, Baidoe-Ansah D, Wlodarczyk J, Kaushik R, et al. Microglia depletion-induced remodeling of extracellular matrix and excitatory synapses in the hippocampus of adult mice. Cells 2021;10:1862.","journal-title":"Cells"},{"key":"2529_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-134","volume":"11","author":"RTY Haw","year":"2014","unstructured":"Haw RTY, Tong CK, Yew A, Lee HC, Phillips JB, Vidyadaran S. A three-dimensional collagen construct to model lipopolysaccharide-induced activation of BV2 microglia. J Neuroinflammation. 2014;11:134.","journal-title":"J Neuroinflammation"},{"key":"2529_CR56","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb9888","volume":"7","author":"J Zhang","year":"2021","unstructured":"Zhang J, Rong P, Zhang L, He H, Zhou T, Fan Y, et al. IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis. Sci Adv. 2021;7:eabb9888.","journal-title":"Sci Adv"},{"key":"2529_CR57","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1002\/glia.22858","volume":"63","author":"K Sato","year":"2015","unstructured":"Sato K. Effects of microglia on neurogenesis. Glia. 2015;63:1394\u2013405.","journal-title":"Glia"},{"key":"2529_CR58","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3222","volume":"356","author":"D Gosselin","year":"2017","unstructured":"Gosselin D, Skola D, Coufal NG, Holtman IR, Schlachetzki JCM, Sajti E, et al. An environment-dependent transcriptional network specifies human microglia identity. Science 2017;356:eaal3222.","journal-title":"Science"},{"key":"2529_CR59","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1016\/j.stem.2021.08.015","volume":"28","author":"G Popova","year":"2021","unstructured":"Popova G, Soliman SS, Kim CN, Keefe MG, Hennick KM, Jain S, et al. Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids. Cell Stem Cell. 2021;28:2153\u201366.e6.","journal-title":"Cell Stem Cell"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02529-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02529-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02529-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T15:02:22Z","timestamp":1727103742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-024-02529-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":59,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["2529"],"URL":"https:\/\/doi.org\/10.1038\/s41380-024-02529-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1980131\/v1","asserted-by":"object"}]},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]},"assertion":[{"value":"20 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}