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Open Access Highly Accessed Study protocol

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

Denise Bernier1*, Jacob Cookey1, David McAllindon1, Robert Bartha2, Christopher C Hanstock3, Aaron J Newman14, Sherry H Stewart14 and Philip G Tibbo14

Author Affiliations

1 Department of Psychiatry, Dalhousie University, 5909 Veterans’ Memorial Lane, Abbie J. Lane Building, Room 3030, Halifax B3H 2E2, Nova Scotia, Canada

2 Robarts Research Institute, Western University, 100 Perth Drive, London N6A 5K8, Ontario, Canada

3 Department of Biomedical Engineering, University of Alberta, 8308-114 Street, Edmonton T6G 2V2, Alberta, Canada

4 Department of Psychology and Neuroscience, Dalhousie University, Box 15000, Life Sciences Centre, B3H 4R2 Halifax, Nova Scotia, Canada

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BMC Psychiatry 2013, 13:264  doi:10.1186/1471-244X-13-264

Published: 17 October 2013

Abstract

Background

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain.

Methods/Design

Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus.

Discussion

We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.

Keywords:
Schizophrenia; Cannabis; White matter; N-acetylaspartate; Oligodendrocytes; Transverse relaxation time constants; Proton magnetic resonance spectroscopy; Diffusion tensor imaging