B4650 - The glue that holds the pieces together Unlocking Cognitive Health in Psychotic Disorders - 15/07/2024

B number: 
B4650
Principal applicant name: 
Neil Davies | UCL (UK)
Co-applicants: 
Esther Walton, Joesph Hayes
Title of project: 
“The glue that holds the pieces together”: Unlocking Cognitive Health in Psychotic Disorders
Proposal summary: 

Psychotic disorders like schizophrenia have a strong neurodevelopmental component, yet symptoms often do not emerge until adolescence or early adulthood. Cognitive impairments are among the earliest and most disabling symptoms. Intriguingly, our research reveals that many brain alterations linked to these impairments resemble those associated with premature aging, such as brain atrophy and advanced brain age. Understanding the neurodevelopmental pathways of these cognitive impairments is crucial for creating effective early interventions.
Our aim is to combat cognitive impairment in psychotic disorders as early as possible by:
1) Understanding the developmental features of brain age acceleration in psychotic disorders and what risk factors might exacerbate these, using large-scale neuroimaging datasets and computationally advanced methods;
2) Characterising the neuronal changes associated with advanced brain age, using experimental mouse models for schizophrenia;
3) Identifying treatment targets that could prevent or slow down cognitive impairment in psychotic disorders, using longitudinal proteomic samples (of individuals who later went on to develop psychosis).
Our goal is to unravel advanced brain age at a neuronal level, embed this within a neurodevelopmental framework, and identify effective treatment targets for early intervention against cognitive impairments in psychotic disorders to mitigate cognitive impairments at the earliest stages of the disease.

Impact of research: 
We could identify risk prediction models and potential molecular mechanisms that predict and explain disease, this may provide clues about future effective treatments.
Date proposal received: 
Monday, 1 July, 2024
Date proposal approved: 
Tuesday, 2 July, 2024
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Proteomics, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Childhood - childcare, childhood adversity, Cognition - cognitive function, Genetic epidemiology, Genetics, Genomics