Abstract
BackgroundA 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/DesignYoung 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.DiscussionWe 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.
Highlights
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
There is a growing body of evidence suggesting that a disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, are responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia [6]
The aim is to generate, from these in vivo data, a plausible interpretation of the specific cellular abnormalities associated with schizophrenia, which might differ from those associated with early adolescent onset of regular cannabis use
Summary
We hereby propose to differentiate the detrimental impact of early adolescent cannabis use from the cellular changes associated with schizophrenia, in order to refine the current understanding of the specific cellular mechanisms involved in white matter abnormalities in the early phase of schizophrenia [64]. DB and JC made a substantial contribution to the initial writing of the draft proposal. DM made a substantial contribution to all MR technical aspects of this proposal namely, pre-testing of MR data quality; computing of the decay curves and T2 relaxation time constants; and all aspects of compilation of MR data. CH has designed the relaxometry parameters for acquisition and offline analyses; he provided a custommade program to assess the decay curves. RB and CH made a substantial intellectual contribution to the writing of the 1H-MRS technical part of the proposal. AN has designed the DTI section of the proposal in terms of data acquisition parameters and offline analyses as well as writing of this technical section. All authors have made intellectual contributions to the writing and editing of the full study proposal.
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