Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

Biol Psychiatry. 2013 Mar 1;73(5):482-91. doi: 10.1016/j.biopsych.2012.10.002. Epub 2012 Nov 28.


Background: Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD.

Methods: The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts.

Results: Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort.

Conclusions: Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aging / physiology*
  • Brain / pathology*
  • Brain Mapping
  • Depressive Disorder, Major / pathology*
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / pathology*
  • Schizophrenia / pathology*