Background
Rationale
Neuroimaging modalities and review of the literature
Diffusion tensor imaging (DTI)
DTI in early phase schizophrenia
DTI in cannabis users without schizophrenia
DTI in cannabis users with schizophrenia
Proton magnetic resonance spectroscopy (1H-MRS)
1H-MRS: technical limitation
Previous relevant 1H-MRS studies
Transverse (T2) relaxation time constants
Previous studies
Aims
Methods/Design
Sample size and groups/subgroups
A priori premises
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In the clinical group (n = 120), T2 time constants of NAA will be reduced relative to healthy controls (n = 120), while T2 time constants of tissue water will be prolonged (replication data) [75, 88, 89]. In addition, the clinical subgroup of early cannabis users (n = 40) will display a greater level of deviation from normative data (non-user healthy controls; n = 40) compared with the two other clinical subgroups (novel data).
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In the healthy control group, similar findings (as above) will be observed in early cannabis users (n = 40) relative to non-users (n = 40), but not in late cannabis users (n = 40) relative to non-users (novel data).
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In the clinical group (n = 120), reduced FA values and NAA levels might or might not be observed relative to healthy controls (n = 120), as previous findings are mixed and inconclusive; however, the clinical subgroup of early cannabis users will display reduced FA values and NAA levels relative to normative data and relative to the two other clinical subgroups (novel data).
Statistical power analyses
Operational definitions
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Early phase schizophrenia: less than 5 years since diagnosis of psychosis with initiation of appropriate medical treatment [20].
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Regular cannabis use: usage occurring on 3 or more days per week, maintained for a period of 6 months or more [34].
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Minimal or non-cannabis users: people who are cannabis-naive or who had minimal experimentation with cannabis (less than 10 experimentations over lifetime) [57].
Recruitment and diagnosis
Inclusion and exclusion criteria
Ethics approval and financial support
Questionnaires and interviews
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The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis 1 (SCID-1) [91] is a semi-structured interview used for diagnosis.
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The Personal and Social Performance scale (PSP) was developed to measure social functioning in schizophrenia, separate from psychological symptoms [94].
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Detailed information about past and current use of all types of illicit drugs, alcohol, and cigarette smoking is collected using a custom Drug Questionnaire, which includes all the questions provided in the SCID but organized in a much more detailed way. Cumulative usage of cannabis will be estimated (in grams) for two time periods: before age 17 (when applicable) and cumulative lifetime.
Neuroimaging
MR online acquisitions
Type | Parameters | Min |
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Localizer and calibration | 2 | |
3D SPGR T1-weighted, for online placement of VOI and its offline tissue segmentation | 256 x 256 matrix; 170 sagittal slices; 1 mm isotropic resolution, no inter-slice gap; TR = 11.3 s; TE = 4.2 ms; flip angle = 20 deg. | 7 |
1H-MRS volume of interest (VOI) | Online VOI placement; shimming (values are carried over to each subsequent 1H-MRS acquisition) | 6 |
NAA concentration levels and T2 time constants of NAA | PRESS; TR = 3 s; TEs = 80, 120, 180, 350, 600 ms; NEX = 64 | 25 |
T2 time constants of water | TR = 10 s; TEs = 50, 60, 80, 120, 180, 350, 600, 800, 1000 ms; NEX = 4 | 20 |
Diffusion-weighted images | TR = 8.5 s; TE 80–90 ms; flip angle = 90 deg; 54 non-collinear diffusion weighting directions, b-factor of 1000 s/mm2; 6 acquisitions, b-factor of ~ 0 s/mm2; 256 x 256 matrix; 260 FOV; 1.02 x 1.02 x 3 mm3 voxels; NEX = 1; acquisition of field maps. | 25 |