Temporal stability of functional neuroimaging findings in psychosis
Research type
Research Study
Full title
Functional MRI biomarkers of psychosis: temporal stability
IRAS ID
154676
Contact name
Philip McGuire
Contact email
Sponsor organisation
King's College London
Research summary
Psychosis is a severe mental health condition which has been until relatively recently thought to be due to a primary deficit in the dopamine neurotransmitter system. However data from large clinical samples confirmed the clinical observation that an overwhelming proportion of the patients have limited or no response to dopamine blockade. This has lead to proposals that an abnormality in a different neurotransmitter system, glutamate, leads to the observed dopamine deficits.
A number of studies employing functional neuroimaging methods have established direct evidence for glutamatergic abnormalities in psychotic disorders. Specifically, MRI based techniques have shown abnormal glutamate levels and blood perfusion in the prefrontal cortex as well as abnormal patterns of connectivity between prefrontal cortex and other cortical structures (Marsman et al. 2013). The significance of these findings is underlined by studies showing alterations in the relationship between glutamatergic and striatal dopamine function (Stone et al. 2010). These developments have raised expectations that functional neuroimaging methods will play and important role in early evaluation of novel mechanism of action (Poels et al. 2014).
The main limitations of these studies has been that they are exclusively of cross-sectional nature. Use of MRI biomarkers in psychosis drug development is therefore limited by the lack of clarity as to whether these measures fluctuate in time and if they do what these changes are due to.
We plan to investigate the temporal stability of three of the main functional MRI techniques: 1H-MRS (spectroscopy, used to compare glutamate metabolites in specific cortical regions), arterial spin labelling (technique to assess blood flow) and BOLD (method to investigate connectivity between brain regions). We plan to recruit 30 patients who will proceed to attend two appointments 6 weeks apart. We hypothesise that the neuroimaging findings will remain stable over the 6 week period.
REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
14/EM/1056
Date of REC Opinion
10 Jul 2014
REC opinion
Further Information Favourable Opinion