Neurobiology of cognitive function
Research type
Research Study
Full title
Investigating the neurobiology of cognitive function in psychotic and affective disorders
IRAS ID
210962
Contact name
Oliver Howes
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Psychotic disorders, including schizophrenia, affect >1% of the population and are one of the highest causes of global disability. Cognitive impairment associated with schizophrenia and related psychotic disorders (CIAS) is common, and is associated with reduced quality of life measures. Our understanding and treatment of CIAS represents an on-going challenge for psychiatry. This is reflected by the ‘MATRICS’ (Measurement and Treatment Research to Improve Cognition in Schizophrenia) initiative, supported by the National Institute of Mental Health.
There is growing evidence that the brain chemical histamine is important for healthy cognitive function, and may be disrupted in mental health disorders. Animal studies suggest that the histamine-3 receptor plays a role in multiple cognitive domains. Moreover, a recent post-mortem study found that patients with schizophrenia had higher levels of histamine-3 receptors in the frontal cortex compared with healthy subjects or patients with a history of depression, and that histamine-3 levels correlated with severity of psychotic symptoms.
In the present study we wish to investigate the neurobiological basis of CIAS, with a focus on the histamine-3 receptor. We propose to measure brain levels of histamine-3 receptors in three groups of subjects: (1) patients with schizophrenia and related psychotic disorders, (2) patients with mood disorders (e.g. depression), and (3) healthy volunteers, using positron emission tomography (PET) and the specific histamine-3 ligand 11C-MK-8278. PET is the only technique that allows measurement of brain function at the level of the molecule and receptor in vivo. We will investigate whether histamine3 receptor levels differ between patients with psychotic disorder and controls, and whether levels are related to cognitive impairment and brain function (as measured using standardised tests and functional magnetic resonance imaging). We hope that these findings will improve our understanding of CIAS, and lead towards finding new treatments for this symptom domain.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
17/LO/1299
Date of REC Opinion
10 Oct 2017
REC opinion
Further Information Favourable Opinion