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  • Gracias, J. (author)

Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-11-03
  • Springer Science and Business Media LLC,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/321544
  • https://gup.ub.gu.se/publication/321544URI
  • https://doi.org/10.1038/s41467-022-33797-6DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-487968URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:151282760URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia. Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.

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  • Orhan, F.Karolinska Institutet (author)
  • Hörbeck, Elin,1984Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xhelic (author)
  • Holmén Larsson, Jessica,1971Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xhojes (author)
  • Khanlarkani, N. (author)
  • Malwade, S.Karolinska Institutet (author)
  • Goparaju, S. K. (author)
  • Schwieler, L.Karolinska Institutet (author)
  • Demirel, I. S. (author)
  • Fu, T. (author)
  • Fatourus-Bergman, H. (author)
  • Pelanis, A. (author)
  • Goold, C. P. (author)
  • Goulding, A.Gothenburg University,Göteborgs universitet,Extern,Psykologiska institutionen,External,Department of Psychology (author)
  • Annerbrink, K. (author)
  • Isgren, AnniellaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xisgan (author)
  • Sparding, TimeaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xspati (author)
  • Schalling, M. (author)
  • Yanez, V. A. C. (author)
  • Gopfert, J. C. (author)
  • Nilsson, Johanna,1993Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xnijoy (author)
  • Brinkmalm, AnnGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xbrian (author)
  • Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xbleka (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xzethe (author)
  • Engberg, G.Karolinska Institutet (author)
  • Piehl, F. (author)
  • Sheridan, S. D. (author)
  • Perlis, R. H. (author)
  • Cervenka, SimonKarolinska Institutet,Uppsala universitet,Psykiatri(Swepub:uu)simce160 (author)
  • Erhardt, S.Karolinska Institutet (author)
  • Landén, Mikael,1966Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlandt (author)
  • Sellgren, C. M. (author)
  • Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi (creator_code:org_t)

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  • In:Nature Communications: Springer Science and Business Media LLC13:12041-1723

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