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A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia

Published online by Cambridge University Press:  22 October 2007

V. Cheung
Affiliation:
Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R.China
C. Cheung
Affiliation:
Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R.China
G. M. McAlonan
Affiliation:
Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R.China State Key Laboratory for Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, S.A.R.China
Y. Deng
Affiliation:
Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R.China
J. G. Wong
Affiliation:
Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R.China
L. Yip
Affiliation:
Department of Radiology, Queen Mary Hospital, Pokfulam, S.A.R.China
K. S. Tai
Affiliation:
Department of Radiology, Queen Mary Hospital, Pokfulam, S.A.R.China
P. L. Khong
Affiliation:
State Key Laboratory for Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, S.A.R.China Department of Radiology, Queen Mary Hospital, Pokfulam, S.A.R.China
P. Sham
Affiliation:
Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R.China State Key Laboratory for Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, S.A.R.China
S. E. Chua*
Affiliation:
Department of Psychiatry, The University of Hong Kong, Pokfulam, S.A.R.China State Key Laboratory for Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, S.A.R.China
*
*Address for correspondence: Dr Siew-eng Chua, Department of Psychiatry Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong. (Email: [email protected])

Abstract

Background

Diffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.

Method

Subjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.

Results

In patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.

Conclusions

Widespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2007

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References

Andreasen, NC, Arndt, S, Swayze, V, Cizadlo, T, Flaum, M, O'Leary, D, Ehrhardt, JC, Yuh, WT (1994). Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science 266, 294298.CrossRefGoogle ScholarPubMed
APA (1994). Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Washington, DC.Google Scholar
Ardekani, BA, Nierenberg, J, Hoptman, MJ, Javitt, DC, Lim, KO (2003). MRI study of white matter diffusion anisotropy in schizophrenia. Neuroreport 14, 20252029.CrossRefGoogle ScholarPubMed
Ashburner, J, Friston, KJ (2000). Voxel-based morphometry: the methods. Neuroimage 11, 805821.CrossRefGoogle ScholarPubMed
Basser, PJ (1995). Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. Nuclear Magnetic Resonance in Biomedicine 8, 333344.Google ScholarPubMed
Basser, PJ, Mattiello, J, LeBihan, D (1994). MR diffusion tensor spectroscopy and imaging. Biophysics Journal 66, 259267.CrossRefGoogle ScholarPubMed
Basser, PJ, Pierpaoli, C (1996). Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. Journal of Magnetic Resonance B 111, 209219.CrossRefGoogle ScholarPubMed
Benes, FM (1993). The relationship between structural brain imaging and histopathologic findings in schizophrenia research. Harvard Review of Psychiatry 1, 100109.CrossRefGoogle ScholarPubMed
Brett, M (2002). The MNI Brain and the Talairach Atlas. MRC Cognition and Brain Sciences Unit: Cambridge.Google Scholar
Bullmore, ET, Woodruff, PWR, Wright, IC, Rabe-Hesketh, S, Howard, RJ, Shuriquie, N, Murray, RM (1998). Does dysplasia cause anatomical dysconnectivity in schizophrenia? Schizophrenia Research 30, 127135.CrossRefGoogle ScholarPubMed
Burns, J, Job, D, Bastin, ME, Whalley, H, Macgillivray, T, Johnstone, EC, Lawrie, SM (2003). Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study. British Journal of Psychiatry 182, 439443.CrossRefGoogle ScholarPubMed
Catani, M (2006). Diffusion tensor magnetic resonance imaging tractography in cognitive disorders. Current Opinion in Neurology 19, 599606.CrossRefGoogle ScholarPubMed
Catani, M, ffytche, DH (2005). The rises and falls of disconnection syndromes. Brain 128, 22242239.CrossRefGoogle ScholarPubMed
Chua, SE, Cheung, C, Cheung, V, Tsang, JT, Chen, EY, Wong, JC, Cheung, JP, Yip, L, Tai, KS, Suckling, J, McAlonan, GM (2007). Cerebral grey, white matter and CSF in never-medicated, first-episode schizophrenia. Schizophrenia Research 89, 1221.CrossRefGoogle ScholarPubMed
DeLisi, LE, Szulc, KU, Bertisch, H, Majcher, M, Brown, K, Bappal, A, Branch, CA, Ardekani, BA (2006). Early detection of schizophrenia by diffusion weighted imaging. Psychiatry Research 148, 6166.CrossRefGoogle ScholarPubMed
Deutsch, GK, Dougherty, RF, Bammer, R, Siok, WT, Gabrieli, JD, Wandell, B (2005). Children's reading performance is correlated with white matter structure measured by diffusion tensor imaging. Cortex 41, 354363.CrossRefGoogle ScholarPubMed
Eastwood, SL, Harrison, PJ (2003). Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Molecular Psychiatry 8, 769, 821831.CrossRefGoogle ScholarPubMed
Foong, J, Maier, M, Clark, CA, Barker, GJ, Miller, DH, Ron, MA (2000). Neuro-pathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study. Journal of Neurology, Neurosurgery and Psychiatry 68, 242244.CrossRefGoogle Scholar
Foong, J, Symms, MR, Barker, GJ, Maier, M, Miller, DH, Ron, MA (2002). Investigating regional white matter in schizophrenia using diffusion tensor imaging. Neuroreport 13, 333336.CrossRefGoogle ScholarPubMed
Gaser, C, Nenadic, I, Buchsbaum, BR, Hazlett, EA, Buchsbaum, MS (2004). Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex. American Journal of Psychiatry 161, 154156.CrossRefGoogle ScholarPubMed
Genovese, CR, Lazar, NA, Nichols, T (2002). Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15, 870878.CrossRefGoogle ScholarPubMed
Giedd, JN, Blumenthal, J, Jeffries, NO, Rajapakse, JC, Vaituzis, AC, Liu, H, Berry, YC, Tobin, M, Nelson, J, Castellanos, FX (1999). Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study. Progress in Neuropsychopharmacology and Biological Psychiatry 23, 571588.Google ScholarPubMed
Gilmore, JH, Zhai, G, Wilber, K, Smith, JK, Lin, W, Gerig, G (2004). 3 Tesla magnetic resonance imaging of the brain in newborns. Psychiatry Research 132, 8185.CrossRefGoogle ScholarPubMed
Gupta, RK, Hasan, KM, Trivedi, R, Pradhan, M, Das, V, Parikh, NA, Narayana, PA (2005). Diffusion tensor imaging of the developing human cerebrum. Journal of Neuroscience Research 81, 172178.CrossRefGoogle ScholarPubMed
Hafner, HR (1992). IRAOS: an instrument for the assessment of the onset and early course of schizophrenia. Schizophrenia Research 6, 209223.CrossRefGoogle ScholarPubMed
Hao, Y, Liu, Z, Jiang, T, Gong, G, Liu, H, Tan, L, Kuang, F, Xu, L, Yi, Y, Zhang, Z (2006). White matter integrity of the whole brain is disrupted in first-episode schizophrenia. Neuroreport 17, 2326.CrossRefGoogle ScholarPubMed
Hardin, RH, Sloane, NJA, Smith, WD (1997). Minimal Energy Arrangements of Points on a Sphere (www.research.att.com/~njas/electrons/). Accessed 26 July 2007.Google Scholar
Hoptman, MJ, Ardekani, BA, Butler, PD, Nierenberg, J, Javitt, DC, Lim, KO (2004). DTI and impulsivity in schizophrenia: a first voxelwise correlational analysis. Neuroreport 15, 24672470.CrossRefGoogle ScholarPubMed
Hubl, D, Koenig, T, Strik, W, Federspiel, A, Kreis, R, Boesch, C, Maier, SE, Schroth, G, Lovblad, K, Dierks, T (2004). Pathways that make voices: white matter changes in auditory hallucinations. Archives of General Psychiatry 61, 658668.CrossRefGoogle ScholarPubMed
Jones, DK, Symms, MR, Cercignani, M, Howard, RJ (2005). The effect of filter size on VBM analyses of DT-MRI data. Neuroimage 26, 546554.CrossRefGoogle ScholarPubMed
Kalus, P, Buri, C, Slotboom, J, Gralla, J, Remonda, L, Dierks, T, Strik, WK, Schroth, G, Kiefer, C (2004). Volumetry and diffusion tensor imaging of hippocampal subregions in schizophrenia. Neuroreport 15, 867871.CrossRefGoogle ScholarPubMed
Kalus, P, Slotboom, J, Gallinat, J, Federspiel, A, Gralla, J, Remonda, L, Strik, WK, Schroth, G, Kiefer, C (2005). New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study. Neuroimage 24, 11221129.CrossRefGoogle ScholarPubMed
Kanaan, RA, Kim, JS, Kaufmann, WE, Pearlson, GD, Barker, GJ, McGuire, PK (2005). Diffusion tensor imaging in schizophrenia. Biological Psychiatry 58, 921929.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.CrossRefGoogle ScholarPubMed
Kubicki, M, Park, H, Westin, CF, Nestor, PG, Mulkern, RV, Maier, SE, Kikinis, R, Jolesz, FA, McCarley, RW, Shenton, ME (2005). DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity. Neuroimage 26, 11091118.CrossRefGoogle ScholarPubMed
Kubicki, M, Westin, CF, Nestor, PG, Wible, CG, Frumin, M, Maier, SE, Kikinis, R, Jolesz, FA, McCarley, RW, Shenton, ME (2003). Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study. Biological Psychiatry 54, 11711180.CrossRefGoogle ScholarPubMed
Kumra, S, Ashtari, M, Cervellione, KL, Henderson, I, Kester, H, Roofeh, D, Wu, J, Clarke, T, Thaden, E, Kane, JM, Rhinewine, J, Lencz, T, Diamond, A, Ardekani, BA, Szeszko, PR (2005). White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study. Journal of the American Academy of Child and Adolescent Psychiatry 44, 934941.CrossRefGoogle ScholarPubMed
Laruelle, M (2000). The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Research Reviews 31, 371384.CrossRefGoogle ScholarPubMed
Leung, LH, Ooi, GC, Kwong, DL, Chan, GC, Cao, G, Khong, PL (2004). White-matter diffusion anisotropy after chemo-irradiation: a statistical parametric mapping study and histogram analysis. Neuroimage 21, 261268.CrossRefGoogle ScholarPubMed
Masutani, Y (2007). Diffusion Tensor Visualizer Version II (www.ut-radiology.umin.jp/people/masutani/dTV.htm). Accessed 26 July 2007.Google Scholar
Masutani, Y, Aoki, S, Abe, O, Hayashi, N, Otomo, K (2003). MR diffusion tensor imaging: recent advance and new techniques for diffusion tensor visualization. European Journal of Radiology 46, 5366.CrossRefGoogle ScholarPubMed
Moseley, M (2002). Diffusion tensor imaging and aging: a review. Nuclear Magnetic Resonance in Biomedicine 15, 553560.Google ScholarPubMed
Price, G, Bagary, MS, Cercignani, M, Altmann, DR, Ron, MA (2005). The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study. Journal of Neurology, Neurosurgery and Psychiatry 76, 585587.CrossRefGoogle ScholarPubMed
Price, G, Cercignani, M, Parker, GJ, Altmann, DR, Barnes, TR, Barker, GJ, Joyce, EM, Ron, MA (2007). Abnormal brain connectivity in first-episode psychosis: a diffusion MRI tractography study of the corpus callosum. Neuroimage 35, 458466.CrossRefGoogle ScholarPubMed
Rascol, O, Payoux, P, Ory, F, Ferreira, JJ, Brefel-Courbon, C, Montastruc, JL (2003). Limitations of current Parkinson's disease therapy. Annals of Neurology 53 (Suppl. 3), S3S12.CrossRefGoogle ScholarPubMed
Rose, SE, Chalk, JB, Janke, AL, Strudwick, MW, Windus, LC, Hannah, DE, McGrath, JJ, Pantelis, C, Wood, SJ, Mowry, BJ (2006). Evidence of altered prefrontal-thalamic circuitry in schizophrenia: an optimized diffusion MRI study. Neuroimage 32, 1622.CrossRefGoogle ScholarPubMed
Schmithorst, VJ, Wilke, M, Dardzinski, BJ, Holland, SK (2005). Cognitive functions correlate with white matter architecture in a normal pediatric population: a diffusion tensor MRI study. Human Brain Mapping 26, 139147.CrossRefGoogle Scholar
Schneider, JF, Il'yasov, KA, Hennig, J, Martin, E (2004). Fast quantitative diffusion-tensor imaging of cerebral white matter from the neonatal period to adolescence. Neuroradiology 46, 258266.CrossRefGoogle ScholarPubMed
Shenton, ME, Dickey, CC, Frumin, M, McCarley, RW (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 152.CrossRefGoogle ScholarPubMed
Shin, YW, Kwon, JS, Ha, TH, Park, HJ, Kim, DJ, Hong, SB, Moon, WJ, Lee, JM, Kim, IY, Kim, SI, Chung, EC (2006). Increased water diffusivity in the frontal and temporal cortices of schizophrenic patients. Neuroimage 30, 12851291.CrossRefGoogle ScholarPubMed
Sowell, ER, Thompson, PM, Holmes, CJ, Jernigan, TL, Toga, AW (1999). In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience 2, 859861.CrossRefGoogle ScholarPubMed
Specht, K, Minnerop, M, Muller-Hubenthal, J, Klockgether, T (2005). Voxel-based analysis of multiple-system atrophy of cerebellar type: complementary results by combining voxel-based morphometry and voxel-based relaxometry. Neuroimage 25, 287293.CrossRefGoogle ScholarPubMed
Steel, RM, Bastin, ME, McConnell, S, Marshall, I, Cunningham-Owens, DG, Lawrie, SM, Johnstone, EC, Best, JJ (2001). Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls. Psychiatry Research 106, 161170.CrossRefGoogle ScholarPubMed
Styner, MA, Charles, HC, Park, J, Guerig, G (2002). Multisite Validation of Image Analysis Methods: Assessing Intra- and Intersite Variability. Image Processing: USA.Google Scholar
Sun, Z, Wang, F, Cui, L, Breeze, J, Du, X, Wang, X, Cong, Z, Zhang, H, Li, B, Hong, N, Zhang, D (2003). Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study. Neuroreport 14, 18331836.CrossRefGoogle ScholarPubMed
Szeszko, PR, Ardekani, BA, Ashtari, M, Kumra, S, Robinson, DG, Sevy, S, Gunduz-Bruce, H, Malhotra, AK, Kane, JM, Bilder, RM, Lim, KO (2005). White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study. American Journal of Psychiatry 162, 602605.CrossRefGoogle ScholarPubMed
Szeszko, PR, Vogel, J, Ashtari, M, Malhotra, AK, Bates, J, Kane, JM, Bilder, RM, Frevert, T, Lim, K (2003). Sex differences in frontal lobe white matter microstructure: a DTI study. Neuroreport 14, 24692473.CrossRefGoogle ScholarPubMed
Thompson, PM, Giedd, JN, Woods, RP, MacDonald, D, Evans, AC, Toga, AW (2000). Growth patterns in the developing brain detected by using continuum mechanical tensor maps. Nature 404, 190193.CrossRefGoogle ScholarPubMed
Thompson, PM, Vidal, C, Giedd, JN, Gochman, P, Blumenthal, J, Nicolson, R, Toga, AW, Rapoport, JL (2001). Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proceedings of the National Academy of Sciences of the United States of America 98, 1165011655.CrossRefGoogle ScholarPubMed
Weinberger, DR, Lipska, BK (1995). Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. Schizophrenia Research 16, 87110.CrossRefGoogle ScholarPubMed
Woodruff, PW, Wright, IC, Shuriquie, N, Russouw, H, Rushe, T, Howard, RJ, Graves, M, Bullmore, ET, Murray, RM (1997). Structural brain abnormalities in male schizophrenics reflect fronto-temporal dissociation. Psychological Medicine 27, 12571266.CrossRefGoogle ScholarPubMed
Wright, IC, Rabe-Hesketh, S, Woodruff, PW, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 1625.CrossRefGoogle ScholarPubMed
Wright, IC, Sharma, T, Ellison, ZR, McGuire, PK, Friston, KJ, Brammer, MJ, Murray, PM, Bullmore, ET (1999). Supra-regional brain systems and the neuropathology of schizophrenia. Cerebral Cortex 9, 366378.CrossRefGoogle ScholarPubMed