State-dependent microstructural white matter changes in drug-naïve patients with first-episode psychosis

Psychol Med. 2017 Nov;47(15):2613-2627. doi: 10.1017/S0033291717001015. Epub 2017 Aug 22.

Abstract

Background: Diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) microstructural abnormalities in schizophrenia. Whether or not such alterations could vary depending on clinical status (i.e. acute psychosis v. remission) remains to be investigated.

Methods: Twenty-five treatment-naïve first-episode psychosis (FEP) patients and 51 healthy-controls (HC) underwent MRI scanning at baseline. Twenty-one patients were re-scanned as soon as they achieved sustained remission of symptoms; 36 HC were also scanned twice. Rate-of-change maps of longitudinal DTI changes were calculated for in order to examine WM alterations associated with changes in clinical status. We conducted voxelwise analyses of fractional anisotropy (FA) and trace (TR) maps.

Results: At baseline, FEP presented reductions of FA in comparison with HC [p < 0.05, false-discovery rate (FDR)-corrected] affecting fronto-limbic WM and associative, projective and commissural fasciculi. After symptom remission, patients showed FA increase over time (p < 0.001, uncorrected) in some of the above WM tracts, namely the right anterior thalamic radiation, right uncinate fasciculus/inferior fronto-occipital fasciculus, and left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. We also found significant correlations between reductions in PANSS scores and FA increases over time (p < 0.05, FDR-corrected).

Conclusions: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities in brain tracts are a key neurobiological feature of acute psychotic disorders, and recovery from such WM pathology can lead to amelioration of symptoms.

Keywords: Antipsychotic; diffusion tensor imaging; disease phase; first-episode psychosis; schizophrenia; white matter.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Diffusion Tensor Imaging / methods*
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Psychotic Disorders / diagnostic imaging
  • Psychotic Disorders / pathology*
  • Psychotic Disorders / physiopathology*
  • Psychotic Disorders / therapy
  • Remission Induction
  • White Matter / diagnostic imaging
  • White Matter / pathology*
  • Young Adult