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Nat Commun. 2020 Jan 14;11(1):246. doi: 10.1038/s41467-019-14122-0.

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

Author information

1
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK.
2
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
3
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
4
South London and Maudsley NHS Foundation Trust, Camberwell, London, SE5 8AF, UK.
5
Division of Brain Sciences, Imperial College London, The Commonwealth Building, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
6
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, 5 Cutcombe Road, London, SE5 9RT, UK.
7
Invicro Imaging Services, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.
8
Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
9
MRC Centre for Neurodevelopmental Disorders, King's College London, London, SE1 1UL, UK.
10
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK. oliver.howes@lms.mrc.ac.uk.
11
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, W12 0NN, UK. oliver.howes@lms.mrc.ac.uk.
12
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK. oliver.howes@lms.mrc.ac.uk.
13
South London and Maudsley NHS Foundation Trust, Camberwell, London, SE5 8AF, UK. oliver.howes@lms.mrc.ac.uk.

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.

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