Elsevier

Biological Psychiatry

Volume 58, Issue 12, 15 December 2005, Pages 921-929
Biological Psychiatry

Review
Diffusion Tensor Imaging in Schizophrenia

https://doi.org/10.1016/j.biopsych.2005.05.015Get rights and content

Background

Diffusion tensor imaging (DTI) is a relatively new neuroimaging technique that can be used to examine the microstructure of white matter in vivo. A systematic review of DTI studies in schizophrenia was undertaken to test the hypothesis that DTI can detect white matter differences between schizophrenia patients and normal control subjects.

Methods

EMBASE, PubMed, Medline, and PsychInfo were searched online and key journals were searched manually for studies comparing anisotropy (a measure of white matter integrity) between patients and control subjects. Nineteen articles were systematically reviewed.

Results

Though 16 studies found differences, methodological and data differences prevented a meta-analysis. Fourteen studies found reduced anisotropy in patients; two studies found only a loss of normal asymmetry. The region of investigation varied across studies, however, and when the same region (for example, the cingulum) was examined in different studies, as many failed to find a difference as found one. These inconsistencies may be the result of small sample sizes and differences in methodology.

Conclusions

Diffusion tensor imaging has yet to provide consistent findings of white matter abnormalities in schizophrenia. Its potential as a means of examining anatomical connectivity may be realized with the study of larger, more homogenous groups of subjects and with ongoing improvements in image analysis.

Section snippets

Methods and Materials

Our inclusion criteria were that studies be published in peer-reviewed journals and make anisotropy-based statistical comparisons between schizophrenia patients and control subjects. Letters and abstracts were excluded. Online searches of the databases EMBASE, PubMed, PsychInfo, and Medline were performed, using the search terms schizophrenia, psychosis, diffusion, tensor, DTI, and MRI. An additional manual search was performed on the 2004 issues of those psychiatric and neuroimaging journals

Results

There has been a remarkable proliferation of studies using DTI in schizophrenia. After the first in 1998, there followed one in 1999 and 2000, growing to eight studies in 2003 alone. A total of 19 studies met the inclusion criteria (see Table 1). Four other studies correlated FA values with impulsivity (Hoptman et al 2002, Hoptman et al 2004), negative symptoms (Wolkin et al 2003), and neuropsychological measures (Nestor et al 2004) but did not compare FA with control subjects. One further

Voxel-Based Studies

Overall, though 14 studies found reduced FA in patients with schizophrenia, there was a lack of consistent findings. The variation in the regions examined limits direct comparison in most cases, so we shall focus on the two tracts which have been most studied: the corpus callosum and the cingulum. First, we shall compare the voxel-based studies, which perforce include every region examined by the ROI studies. Foong et al (2002) found no significant differences in their sample of 14 patients,

Discussion

Most DTI studies in schizophrenia found some positive results, though there were many negative results; indeed, for any region where studies found a positive result, at least as many failed to find one. While it is thus possible that there are no real differences in FA between patients with schizophrenia and control subjects, it is also possible that there are real but small (or highly variable) differences but at least some of the studies did not have enough power to detect them (type 2

Conclusion

Diffusion tensor imaging has yet to detect reproducibly consistent FA differences in schizophrenia, although varied methodology prevented direct comparison between most studies. As we are seeking subtle differences that may be relatively small when compared with the variance in current methods, forthcoming studies with larger, more homogenous samples may yet realize the true potential of DTI.

References (79)

  • S. Kumra et al.

    Reduced frontal white matter integrity in early-onset schizophreniaA preliminary study

    Biol Psychiatry

    (2004)
  • K.O. Lim et al.

    Reduced frontal white matter integrity in cocaine dependenceA controlled diffusion tensor imaging study

    Biol Psychiatry

    (2002)
  • H.J. Park et al.

    Spatial normalization of diffusion tensor MRI using multiple channels

    Neuroimage

    (2003)
  • H.J. Park et al.

    White matter hemisphere asymmetries in healthy subjects and in schizophreniaA diffusion tensor MRI study

    Neuroimage

    (2004)
  • A. Pfefferbaum et al.

    Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism

    Neuroimage

    (2002)
  • S.L. Rossell et al.

    Corpus callosum area and functioning in schizophrenic patients with auditory–verbal hallucinations

    Schizophr Res

    (2001)
  • S. Skare et al.

    Noise considerations in the determination of diffusion tensor anisotropy

    Magn Reson Imaging

    (2000)
  • R.M. Steel et al.

    Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls

    Psychiatry Res

    (2001)
  • C.A. Tamminga et al.

    The limbic cortex in schizophreniaFocus on the anterior cingulate

    Brain Res Brain Res Rev

    (2000)
  • W.D. Taylor et al.

    Evidence of white matter tract disruption in MRI hyperintensities

    Biol Psychiatry

    (2001)
  • A.T. Toosy et al.

    Characterizing function-structure relationships in the human visual system with functional MRI and diffusion tensor imaging

    Neuroimage

    (2004)
  • F. Wang et al.

    A diffusion tensor imaging study of middle and superior cerebellar peduncle in male patients with schizophrenia

    Neurosci Lett

    (2003)
  • R. Westerhausen et al.

    The influence of handedness and gender on the microstructure of the human corpus callosumA diffusion-tensor magnetic resonance imaging study

    Neurosci Lett

    (2003)
  • I. Agartz et al.

    Abnormal brain white matter in schizophreniaA diffusion tensor imaging study

    Neuroreport

    (2001)
  • S. Akbarian et al.

    Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients

    Arch Gen Psychiatry

    (1996)
  • A.L. Alexander et al.

    Analysis of partial volume effects in diffusion-tensor MRI

    Magn Reson Med

    (2001)
  • N.C. Andreasen et al.

    “Cognitive dysmetria” as an integrative theory of schizophreniaA dysfunction in cortical-subcortical-cerebellar circuitry?

    Schizophr Bull

    (1998)
  • B.A. Ardekani et al.

    MRI study of white matter diffusion anisotropy in schizophrenia

    Neuroreport

    (2003)
  • K. Arfanakis et al.

    Diffusion tensor MR imaging in diffuse axonal injury

    AJNR Am J Neuroradiol

    (2002)
  • R. Bammer et al.

    Diffusion tensor imaging using single-shot SENSE-EPI

    Magn Reson Med

    (2002)
  • P.J. Basser et al.

    Diffusion-tensor MRITheory, experimental design and data analysis–a technical review

    NMR Biomed

    (2002)
  • P.J. Basser et al.

    In vivo fiber tractography using DT-MRI data

    Magn Reson Med

    (2000)
  • C. Beaulieu

    The basis of anisotropic water diffusion in the nervous system–a technical review

    NMR Biomed

    (2002)
  • S. Begré et al.

    Reduced hippocampal anisotropy related to anteriorization of alpha EEG in schizophrenia

    Neuroreport

    (2003)
  • R.W. Buchanan et al.

    Structural evaluation of the prefrontal cortex in schizophrenia

    Am J Psychiatry

    (1998)
  • M.S. Buchsbaum et al.

    MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia

    Neuroreport

    (1998)
  • E.T. Bullmore et al.

    Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain

    IEEE Trans Med Imaging

    (1999)
  • J. Burns et al.

    Structural disconnectivity in schizophreniaA diffusion tensor magnetic resonance imaging study

    Br J Psychiatry

    (2003)
  • T.D. Cannon et al.

    Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls

    Arch Gen Psychiatry

    (1998)
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