White matter deficits in first episode schizophrenia: an activation likelihood estimation meta-analysis

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:100-6. doi: 10.1016/j.pnpbp.2013.04.019. Epub 2013 May 3.


Background: Diffusion tensor imaging (DTI) has been widely used in psychiatric research and has provided evidence of white matter abnormalities in first episode schizophrenia (FES). The goal of the present meta-analysis was to identify white matter deficits by DTI in FES.

Methods: A systematic search was conducted to collect DTI studies with voxel-wised analysis of the fractional anisotropy (FA) in FES. The coordinates of regions with FA changes were meta-analyzed using the activation likelihood estimation (ALE) method which weighs each study on the basis of its sample size.

Results: A total of 8 primary studies were selected, including 271 FES patients and 297 healthy controls. Among these studies, 52 regions showed reductions in the FA in FES while 2 regions had increased FA. Consistent FA reductions in the white matter of the right deep frontal and left deep temporal lobes were identified in all FES patients relative to healthy controls. Fiber tracking showed that the main tracts involved were the cingulum bundle, the left inferior longitudinal fasciculus, the left inferior fronto-occipital fasciculus and the interhemispheric fibers running through the corpus callosum.

Conclusions: The current findings provide evidence confirming the lack of connection in the fronto-limbic circuitry at the early stages of the schizophrenia. Because the coordinates reported in the primary literature were highly variable, future investigations with large samples would be required to support the identified white matter changes in FES.

Keywords: ALE; DTI; FA; FES; First episode; Fractional anisotropy; IC; Meta-analysis; SDM; Schizophrenia; White matter; activation likelihood estimation; diffusion tensor imaging; first episode schizophrenia; fractional anisotropy; intervoxel coherence; signed differential mapping.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisotropy
  • Case-Control Studies
  • Corpus Callosum / pathology
  • Frontal Lobe / pathology*
  • Humans
  • Likelihood Functions
  • Nerve Fibers, Myelinated / pathology*
  • Neural Pathways / pathology
  • Neuroimaging*
  • Schizophrenia / diagnosis
  • Schizophrenia / pathology*
  • Temporal Lobe / pathology*