SUPPLEMENTARY MATERIAL 2

An overview of Magnetization Transfer Imaging (MTI) studies in schizophrenia

No. (C1) / Study / Sample Overlap (No. in C1) / Approach / Scan / Tissue examined / Controls / Schizophrenia / Abnormalities reported in schizophrenia
N / M/F / Age / N / M/F / Age / Subcategories
1 / Foong 20001 / 2 / ROI (4 lobes and CC) / 1.5 T / Whole Brain / 30 / 22/8 / 35.1 (25-49) / 25 / 19/6 / 37.3 (25-46) / DOI 14.3 (3-22); all medicated / Reduced MTR: Right and left temporal lobe. Effect of cognitive variables not tested
2 / Foong 20012 / 1 / VBA / 1.5 T / Whole Brain / 30 / 22/8 / 35.1 (25-49) / 25 / 19/6 / 37.3 (25-46) / DOI 14.3 (3-22); all medicated / Reduced MTR (all GM): inferior and middle frontal, inferior and middle temporal (both GM and WM), and superior occipital gyri. Effect of cognitive variables not tested
4 / Bagary 20023 / ROI: Thalamus only / 1.5 T / Anatomical ROI / 25 / 19/6 / 35.2 (24-49) / 25 / 19/6 / 37.2 (25-46) / DOI 14.3 years (range 3–22); all medicated / Thalamus only: No MTR abnormalities.Premorbid IQ showed no relationship with MTR measures.
5 / Bagary 20034 / 9 / VBA / 1.5 T / Whole Brain / 30 / 18/12 / (21-49) / 30 / 19/11 / 27.3 (18-47) / First episode; DOI 5.3(1-14) months; 5 unmedicated / Reduced MTR: Right medial PFC, left insula, left uncinate fasciculus. Effect of cognitive variables not tested
6 / Kiefer 20045 / ROI: Hippocampal formation / 1.5 T / Anatomical ROI / 14 / 9/5 / 31.0 (SD 6.5) / 14 / 9/5 / 31.4 (SD 10.8) / DOI 3.31 (3.7) years; All medicated / No MTR differences in Hippocampal ROI. Effect of cognitive variables not tested
7 / Kalus 20056 / ROI: Amygdala only / 1.5 T / Anatomical ROI / 14 / 9/5 / 31.37 (SD:6.0) / 14 / 9/5 / 27.93 (SD 6.4) / DOI 2.22(2.23) years; all medicated / No MTR differences in Amygdala ROI. Effect of cognitive variables not tested.
8 / Antosik-Biernacka 20067 / . / VBA / 3 T / Whole Brain / 23 / 13/10 / 33.9 (25-47) / 20 / 13/7 / 35.5 (23–45) / DOI 10.7 (5.8) years / Reduced MTR: Trend not reaching significance -
Left superior temporal gyrus, Right occipital cortex, and left periventricular WM. Effect of cognitive variables not tested
9 / Price 20068 / 5 / VBA (longitudinal) / 1.5 T / Whole Brain / 12 / 4/8 / 31.6 (26-50) / 16 / 12/4 / 26.3 (16–45) / First episode sample on inception / No longitudinal MTR/WMV changes. Effect of cognitive variables not tested
10 / Kubicki 20059 / VBA / 1.5 T / WM only / 26 / N/A / N/A / 21 / N/A / N/A / N/A / Reduced MTR and FA: Superior occipitofrontal fasciculus, right internal capsule, corpus callosum, fornix. Right posterior CB – reduced MTR, normal FA. FA of CB associated with lower WCST scores.
11 / Price 201010 / VBA / 1.5T / Whole Brain / 47 / 27/20 / 24.8 (16-37) / 48 / 33/15 / 26.2 (16–50) / First episode / Reduced MTR: Right entorhinal cortex, fusiform, dentate and superior frontal gyri and in left superior frontal and inferior/rostral cingulate gyri..Effect of cognitive variables not tested
12 / Mandl 201011 / ROIs: Genu and UF only / 1.5T / Reconstructed WM tracts / 40 / 29/11 / 28.0 (18-45) / 40 / 30/10 / 26.8 (20-41) / DOI 25.1(17.4); all medicated / Increased MTR: Right UF. No differences in FA or RD. Effect of cognitive variables not tested
13 / De Weijer 2011a12 / 14 / ROIs: Average fiber approach (UF, AF, CST, Cingulum) / 3 T / Reconstructed WM tracts / 40 / 23/19 / 38.4 (21-66) / 42 / 25/19 / 36.9 (18-61) / DOI 13.6(12.9)y; 6 unmedicated / Increased MTR: AF bilaterally
Lower FA: UF, CST and AF (no MD, AD differences)
Higher RD: UF,AF,CST, cingulum
Effect of cognitive variables not tested
14 / De Weijer 2011b13 / 13 / ROIs: Average fiber approach (AF, UF, CST, Cingulum) / 3 T / Reconstructed WM tracts / 31 / 14/22 / 41.39 (21-66) / 32 / 14/21 / 39.6 (18-61) / DOI 12.5 years (12.5); 5 unmedicated / Increased MTR: AF bilaterally (associated with lower FA, higher RD on the left)
Effect of cognitive variables not tested
15 / Mandl 201214 / ROIs: 12 WM tracts / 1.5 T / Reconstructed WM tracts / 23 / 14/9 / 22.81 (SD 3.1) / 16 / 13/3 / 23.37 (SD 3.5) / All unmedicated; DOI 1.85(2.14) years / Increased MTR and MD: Right UF and left AF
IQ showed no relationship with MTR measures
16 / Bohner 201215 / VBA (histograms) / 1.5 T / Whole Brain / 29 / 17/12 / 25.7 (SD 5.2) / 16 / 12/4 / 25.8 (SD 5.8) / First episode; 12 unmedicated (UHR samples also studied) / Reduced MTR: Bilateral frontal WM reduction in schizophrenia. Ultra high risk subjects showed MTR reduction in extended amygdala (stria terminalis). Effect of cognitive variables not tested
17 / Bachmann 201216 / VBA / 3 T / Whole Brain / 32 / 21/12 / 33.5 (SD10.1) / 32 / 21/12 / 33.1 (SD 8.6) / Chronic schizophrenia (mean no. of previous episodes = 3); all medicated / Reduced MTR: Right calcarine, lingual and fusiform and inferior temporal, hippocampal regions
Effect of cognitive variables not tested

DOI: Duration of Illness ROI: Region of Interest CC: Corpus Callosum SD: Standard deviation (presented where range is not available) MTR: Magnetisation Transfer Ratio WMV: White Matter Volume GM: Grey Matter FA: Fractional Anisotropy PFC: Prefrontal cortex CB: Cingulum bundle WCST: Wisconsin Card Sorting Test AF: Arcuate Fasciculus UF: Uncinate Fasciculus CST: Corticospinal tract RD: Radial diffusivity AD: Axial diffusivity VBA: Voxel Based Analysis N/A Information not available

REFERENCES

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3. Bagary MS, Foong J, Maier M, duBoulay G, Barker GJ, Miller DH et al. A magnetization transfer analysis of the thalamus in schizophrenia. J Neuropsychiatry Clin Neurosci 2002; 14: 443–8.

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9. Kubicki M, Park H, Westin CF, Nestor PG, Mulkern RV, Maier SE et al. DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity. Neuroimage 2005 Jul 15; 26: 1109–18.

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12. de Weijer AD, Neggers SFW, Diederen KMS, Mandl RCW, Kahn RS, Hulshoff Pol HE et al. Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non-psychotic individuals. Hum Brain Mapp [Internet] 2011 Nov 23 [cited 2012 Jul 29];Available from:

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16. Bachmann S, Haffer S, Beschoner P, Viviani R. Imputation techniques for the detection of microstructural changes in schizophrenia, with an application to magnetization transfer imaging. Schizophr Res 2011 Oct; 132: 91–6.

7T MRI of myelination in schizophrenia