The impact of copy number variants on cortical network dynamics
Research type
Research Study
Full title
The impact of copy number variants on cortical network dynamics (CONVERGE)
IRAS ID
325987
Contact name
Jeremy Hall
Contact email
Sponsor organisation
Cardiff University
Duration of Study in the UK
10 years, 0 months, 1 days
Research summary
Recent major advances in research into the genetic basis of neurodevelopmental disorders offers hope for the rational development of new treatments. One of the most striking genetic findings has been that small changes in chromosomal structure, referred to as Copy Number Variants (CNVs), are major contributors to risk for neurodevelopmental conditions including schizophrenia. Studying patients with these CNVs therefore offers new opportunities into understanding the brain changes associated with risk for the disorder.
In the current proposal we aim to investigate how some of the most common CNVs affect brain function. We hypothesise that these different CNVs have common effects on brain function by altering the regulation of firing of certain types of neurons in the cortex. We further hypothesise that this acts to decrease integrated function of neurons (or “connectivity”) across the brain, contributing to the cognitive difficulties and reality distortion seen in the disorder.
The human brain is difficult to investigate directly because of its relative inaccessibility. We will therefore adopt an integrated approach combining different methods in humans, animals, and neuronal cells to investigate the impact of CNVs on the brain. These different methods will enable us to build up a more complete picture of the way these CNVs cause risk for conditions like schizophrenia and autism than any single technique alone could. However, it remains a challenge to compare and integrate data across these methods. To allow us to do this and to build a better picture of the overall impact of CNVs on the brain we will subsequently develop a computer model of the neural changes associated with risk produced by these CNVs.
Overall, this work will enable us to advance understanding of how CNVs impacts on neuronal function and reduce brain connectivity. The insights we will gain will represent an important step towards improving understanding of the biological causes of schizophrenia and neurodevelopmental disorders building on genetic discovery, with the eventual aim of enhancing the early diagnosis and treatment.
REC name
London - Fulham Research Ethics Committee
REC reference
24/LO/0689
Date of REC Opinion
29 Oct 2024
REC opinion
Further Information Favourable Opinion