In vivo synaptic imaging in schizophrenia
File(s)
Author(s)
Onwordi, Ellis Chika
Type
Thesis
Abstract
Synaptic deficits are hypothesised to play a role in schizophrenia pathogenesis, but this has not yet been tested directly in vivo. In this thesis, I use positron emission tomography with novel radioligand [11C]UCB-J in patients with schizophrenia and healthy volunteers to investigate levels of synaptic vesicle glycoprotein 2A (SV2A), a marker of presynaptic terminal density. First, I demonstrate that levels of SV2A are significantly lower in the frontal and anterior cingulate cortices in chronic schizophrenia subjects compared to healthy volunteers, and that antipsychotic drug exposure is not significantly associated with SV2A levels in patients. Then, indexing glutamate levels using proton magnetic resonance spectroscopy, I show that SV2A and glutamate levels are significantly positively correlated in the anterior cingulate cortex and hippocampus in healthy volunteers, but not in schizophrenia. Finally, I report that deficits in SV2A levels are not present in the early course of schizophrenia compared to healthy controls. Collectively, these findings provide the first direct evidence that presynaptic terminal protein levels are lower in schizophrenia in vivo, and that lower levels are unlikely to be directly accounted for by antipsychotic drug treatment. They indicate that lower presynaptic terminal protein levels arise after illness onset, and may be due to lower levels of glutamatergic synapses and/or a lower proportion of glutamatergic synapses in schizophrenia.
Version
Open Access
Date Issued
2022-05-06
Date Awarded
01/03/2023
License URL
Advisor
Howes, Oliver
Natesan, Sridhar
Publisher Department
Institute of Clinical Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)