Anatomical connectivity in early onset schizophrenia

Lead Research Organisation: University of Oxford
Department Name: Clinical Neurosciences

Abstract

This project looks at brain changes in adolescents with schizophrenia using new and advanced MRI techniques.
Schizophrenia is a major mental illness affecting up to 1% of the population. Often young people are affected. As yet we are uncertain of the causes, although genes and the brain are directly involved. We know that there are changes in a number of areas in the brain, and it is highly likely that the connections or nerve tracts between these brain areas are also abnormal. With MRI we can accurately map these nerve tracts and show how they connect to certain brain regions, particularly those involving speech and language.
We aim to study schizophrenia in adolescence – an age when the brain is still developing. By comparing teenagers with schizophrenia to healthy adolescents, we hope to gather important information on how schizophrenia affects brain development during the vital period of adolescence.  If we can understand which nerve tracts and brain regions are abnormal, and relate this to symptoms, we will be in a better position to develop targeted drug treatments.

Technical Summary

There is accumulating evidence that the cognitive and sensory abnormalities in schizophrenia are related to dysfunction in networks linking the thalamus and the frontal temporal lobes and cerebellum. Diffusion Tensor Magnetic Resonance Imaging (DTI) provides a way of assessing macro-connectivity reflected in white matter projection pathways between these areas . Our pilot study has shown locally reduced FA in the middle temporal gyral region. This project will use voxel-wise measures of anisotropy of white matter (fractional anisotropy, FA) and related methods to distinguish differences in white matter organisation between patients with adolescent onset schizophrenia and age- and sex-matched controls. A new, method of probabilistic tractography now well-validated by our group will be applied to define FA changes specifically in thalamo-frontal, frontal cerebellar and temporal white matter pathways. Study of the early-onset group with a likely neurodevelopmental aetiology will shed light on the crucial aspects of the interaction of the schizophrenic illness and cortical development, which undergoes major reorganisation during adolescence.

Publications

10 25 50

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Douaud G (2014) A common brain network links development, aging, and vulnerability to disease. in Proceedings of the National Academy of Sciences of the United States of America

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Douaud G (2009) Schizophrenia delays and alters maturation of the brain in adolescence. in Brain : a journal of neurology

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James A (2016) Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning. in European psychiatry : the journal of the Association of European Psychiatrists

 
Description FMRIB Centre Oxford 
Organisation John Radcliffe Hospital
Department Centre for Functional MRI of the Brain (fMRI)
Country United Kingdom 
Sector Hospitals 
PI Contribution Collaborative supervision of fellows and research
Collaborator Contribution Collaborative research, support for fellows and students, research environment
Impact Papers since 2006 with FMRIB coauthors
 
Description GlaxoSmithKline Global Imaging Unit 
Organisation GlaxoSmithKline (GSK)
Department GSK Clinical Imaging Centre (CIC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Wellcome Trust-GSK Clinical Fellowships in Translational Medicine
Collaborator Contribution Financial support and co-mentorship for students
Impact 16 clinical fellows have been enrolled or have completed Academic papers and 1 patent have resulted
Start Year 2007
 
Description Psychiatry 
Organisation University of Oxford
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution Helping to define problem, experimental design, analysis, implrementation and interpretation
Collaborator Contribution Staff
Impact Multiple papers- support for new grants to Profs. Cowen and James
Start Year 2006
 
Description Human Brain Mapping 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Poster presentation

considerable interest
Year(s) Of Engagement Activity 2008
 
Description Lecture on science behind creativity for lay audience 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Participation in workshop on creativity
Year(s) Of Engagement Activity 2019
URL https://www.seh.ox.ac.uk/discover/research/centre-for-the-creative-brain-2