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

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, Eugenii A. Rabiner, Roger N. Gunn, Sridhar Natesan, Anthony C. Vernon and Oliver D. Howes ()
Additional contact information
Ellis Chika Onwordi: Hammersmith Hospital
Els F. Halff: King’s College London
Thomas Whitehurst: Hammersmith Hospital
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
Ekaterina Shatalina: Hammersmith Hospital
Tiago Reis Marques: Hammersmith Hospital
Eugenii A. Rabiner: Burlington Danes Building
Roger N. Gunn: Hammersmith Hospital
Sridhar Natesan: Hammersmith Hospital
Anthony C. Vernon: Maurice Wohl Clinical Neuroscience Institute, King’s College London
Oliver D. Howes: Hammersmith Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-14122-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14122-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-14122-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().