Synaptic Density Marker SV2A is Reduced in Schizophrenia Patients and Unaffected by Antipsychotics in Rats

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jan 16

PMID 31937764

Citations 107

Authors

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

Oliver D Howes

Affiliations

Soon will be listed here.

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 [C]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 (V). [C]UCB-J V 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, [H]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.

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