Neuroreceptor regulation of brain structure and function
Research type
Research Study
Full title
Neuroreceptor regulation of brain structure and function
IRAS ID
235384
Contact name
Oliver Howes
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
5 years, 0 months, 2 days
Research summary
The impact of changes in neurotransmitter systems on brain structure has been subject to debate. Some studies suggested that drugs that block the dopamine system (antipsychotics) are neuroprotective. However, others have suggested that they can actually reduce brain volumes and be harmful.
Nevertheless, the majority of evidence has been provided by studies conducted in patients with schizophrenia, where the effect of the illness, social factors and substance misuse is difficult to disentangle. To overcome these confounding factors, preclinical and healthy volunteer studies have been conducted. Studies in monkeys and rats have suggested that these drugs can led to decreases in gray and white matter brain volumes. The data in healthy individuals is scarcer and the majority involved a single exposure to drugs that block dopamine neurotransmission.
Whilst these previous studies have shown that acute single exposure to antipsychotics are associated with alterations in brain structure and function, it remains unknown if these are an acute response that normalises with repeated exposure to these drugs. Moreover it is not known what the contribution of dopamine partial agonism or antagonism at other receptors is to these findings. Determining this is critical to understanding the role of dopamine and other neuroreceptors in regulating brain structure and function, and in determining whether changes seen in patients are due to long-term neuroreceptor antagonism or agonism or a consequence of illness.
In this study we aim to investigate the role of repeated neuroreceptor agonism/antagonism medication in regulating brain structure and function. We will assess the impact of these agonism/antagonism drugs on brain volume, functional connectivity, cerebral blood flow and brain metabolites using MRI and PET measures. Finally, we will investigate if the brain changes are specific to selective D2/3 antagonism or if they are seen with combined D2/3 and 5HT2a antagonism and D2/3 partial or full agonism.REC name
London - West London & GTAC Research Ethics Committee
REC reference
18/LO/1044
Date of REC Opinion
22 Oct 2018
REC opinion
Further Information Favourable Opinion