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Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats

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  • Ellis Chika Onwordi

    (Hammersmith Hospital
    Imperial College London
    King’s College London
    South London and Maudsley NHS Foundation Trust)

  • Els F. Halff

    (King’s College London)

  • Thomas Whitehurst

    (Hammersmith Hospital
    King’s College London
    South London and Maudsley NHS Foundation Trust)

  • Ayla Mansur

    (Hammersmith Hospital)

  • Marie-Caroline Cotel

    (Maurice Wohl Clinical Neuroscience Institute, King’s College London)

  • Lisa Wells

    (Burlington Danes Building)

  • Hannah Creeney

    (Maurice Wohl Clinical Neuroscience Institute, King’s College London)

  • David Bonsall

    (Burlington Danes Building)

  • Maria Rogdaki

    (Hammersmith Hospital
    Imperial College London
    King’s College London
    South London and Maudsley NHS Foundation Trust)

  • Ekaterina Shatalina

    (Hammersmith Hospital
    Imperial College London)

  • Tiago Reis Marques

    (Hammersmith Hospital
    King’s College London
    South London and Maudsley NHS Foundation Trust)

  • Eugenii A. Rabiner

    (Burlington Danes Building
    King’s College London)

  • Roger N. Gunn

    (Hammersmith Hospital
    Burlington Danes Building)

  • Sridhar Natesan

    (Hammersmith Hospital
    King’s College London)

  • Anthony C. Vernon

    (Maurice Wohl Clinical Neuroscience Institute, King’s College London
    King’s College London)

  • Oliver D. Howes

    (Hammersmith Hospital
    Imperial College London
    King’s College London
    South London and Maudsley NHS Foundation Trust)

Abstract

Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis, but this has not been tested directly in vivo. Here, we investigated synaptic vesicle glycoprotein 2A (SV2A) levels and their relationship to symptoms and structural brain measures using [11C]UCB-J positron emission tomography in 18 patients with schizophrenia and 18 controls. We found significant group and group-by-region interaction effects on volume of distribution (VT). [11C]UCB-J VT was significantly lower in the frontal and anterior cingulate cortices in schizophrenia with large effect sizes (Cohen’s d = 0.8-0.9), but there was no significant difference in the hippocampus. We also investigated the effects of antipsychotic drug administration on SV2A levels in Sprague-Dawley rats using western blotting, [3H]UCB-J autoradiography and immunostaining with confocal microscopy, finding no significant effects on any measure. These findings indicate that there are lower synaptic terminal protein levels in schizophrenia in vivo and that antipsychotic drug exposure is unlikely to account for them.

Suggested Citation

  • Ellis Chika Onwordi & Els F. Halff & Thomas Whitehurst & Ayla Mansur & Marie-Caroline Cotel & Lisa Wells & Hannah Creeney & David Bonsall & Maria Rogdaki & Ekaterina Shatalina & Tiago Reis Marques & E, 2020. "Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14122-0
    DOI: 10.1038/s41467-019-14122-0
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    Cited by:

    1. Ralda Nehme & Olli Pietiläinen & Mykyta Artomov & Matthew Tegtmeyer & Vera Valakh & Leevi Lehtonen & Christina Bell & Tarjinder Singh & Aditi Trehan & John Sherwood & Danielle Manning & Emily Peirent , 2022. "The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Jessica Gracias & Funda Orhan & Elin Hörbeck & Jessica Holmén-Larsson & Neda Khanlarkani & Susmita Malwade & Sravan K. Goparaju & Lilly Schwieler & İlknur Ş. Demirel & Ting Fu & Helena Fatourus-Bergma, 2022. "Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Iva Salamon & Yongkyu Park & Terezija Miškić & Janja Kopić & Paul Matteson & Nicholas F. Page & Alfonso Roque & Geoffrey W. McAuliffe & John Favate & Marta Garcia-Forn & Premal Shah & Miloš Judaš & Ja, 2023. "Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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