Characterization of white matter abnormalities in early-stage schizophrenia

Early Interv Psychiatry. 2018 Aug;12(4):660-668. doi: 10.1111/eip.12359. Epub 2016 Sep 13.


Aim: White matter abnormalities have been reported in schizophrenia and may indicate altered cortical network integrity and structural connectivity, which have been hypothesized as key pathophysiological components of this illness. In this study, we aimed to further characterize the nature and progression of white matter alterations during the early stages of the disorder.

Methods: We employed diffusion tensor imaging (DTI) approaches to investigate fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) in 40 patients with schizophrenia and related psychotic disorders (aged 18-30 years) who were within 5 years of illness, along with an age-, sex- and race-matched sample of 21 healthy controls. Relationships with illness duration, lifetime antipsychotic medication exposure and symptom levels were examined.

Results: Patients had lower FA and higher RD than controls in numerous white matter tracts, including the corpus callosum (CC) and the superior longitudinal fasciculus. Illness duration was associated with lower FA and higher RD, most prominently in the CC. No group differences or relationships to illness duration were detected with AD, and no relationships between any DTI measurements and lifetime antipsychotic medication use were found.

Conclusions: This investigation provides evidence of widespread disruptions to structural connectivity in the early stages of schizophrenia. The relationship to illness duration, coupled with an absence of relationships to AD or antipsychotic drug exposure, provides evidence of a progressive disease process, although prospective assessments with repeated DTI measurements are needed to fully characterize the trajectory of white matter abnormalities in this illness.

Keywords: diffusion tensor imaging; disease progression; psychosis; structural connectivity; white matter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anisotropy
  • Antipsychotic Agents / therapeutic use
  • Case-Control Studies
  • Diffusion Tensor Imaging
  • Disease Progression
  • Female
  • Humans
  • Male
  • Prospective Studies
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology*
  • White Matter / pathology*
  • Young Adult


  • Antipsychotic Agents