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Relative gray matter volume maps were calculated for each participant by using
the optimized voxel-based morphometry toolbox for SPM8 ( 
http://www.fil.ion.ucl.ac.uk/spm/software/spm8/
 ). Skeletonized fractional
anisotropy maps were calculated for each participant using tract-based spatial
statistics (  22  ) and the FMRIB diffusion toolkit (  23  ). Further details
on MRI acquisition parameters and image processing can be found in the 
online data supplement

.
Received 26 May 2016
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###  Image Acquisition and Processing
© 2024 American Psychiatric Association
Supplementary analyses were performed to examine the influence of medication
and site on age-related trajectories (see the Methods section in the  online
data supplement

). Atypical antipsychotics (t=−1.9), typical antipsychotics (t=−1.88), and
antidepressants (t=1.16) were not significant predictors of gray matter
volume, although atypical and typical antipsychotics showed a trend for lower
gray matter volume (see Figure S4a in the  data supplement

). Fractional anisotropy was significantly increased in patients medicated
with antidepressants (t=2.32, p=0.02; see Figure S4b in the  data supplement

), but atypical (t=−0.81) and typical (t=−0.81) antipsychotics were not
significant predictors of fractional anisotropy. No significant interactions
were observed between medication category and age. Site showed a significant
main effect on fractional anisotropy (F=5.05, p=0.0005) but not on gray matter
volume (F=0.81). The interaction between site and diagnosis was not a
significant predictor of gray matter volume (F=0.99) or fractional anisotropy
(F=0.77). Site-stratified trajectories of brain aging are shown in Figure S5
in the  data supplement

. Site and the interaction between site and diagnosis were not significant
predictors of age.
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The linear regression model was independently fitted to each voxel making up
the white matter skeleton to localize age-related reductions in fractional
anisotropy to specific white matter pathways.  Figure 4  presents clusters of
significantly reduced fractional anisotropy in schizophrenia relative to
comparison subjects (p<0.05, family-wise error corrected) at seven different
ages, ranging from 25 to 55 years, in increments of 5 years. Consistent with
total fractional anisotropy, significant fractional anisotropy reductions in
schizophrenia did not emerge until age 35. These reductions were primarily
localized to the genu and body of the corpus callosum as well as to temporal
aspects of the superior longitudinal fasciculus at age 35, and then the
reductions became more widespread, extending to white matter tracts of all
cortical lobes and the cerebellum, as age increased (see  Movie 2

in the online edition of this article).
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