Yuan Xiao1, Huaiqiang Sun1, Bo Tao1, Youjin Zhao1, Wenjing Zhang1, Qiyong Gong1, John Adrian Sweeney2, and Su Lui1
1Dept. of Radiology, West China Hospital of Sichuan University, Chengdu, China, 2Dept. of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, United States
Synopsis
Do white matter abnormalities increase over the long-term course of
schizophrenia, and is their trajectory influenced by antipsychotic treatment?
In this cross-sectional study, more alteration of white matter microstructure
were found in long-term but never-treated schizophrenia patients than
duration-matched chronically treated patients. In the genu of the corpus
callosum, there was an accelerated age-related reduction of fiber tract integrity
in the never-treated patients. The more attenuated white matter changes in the
treated patient group suggests that long-term antipsychotic treatment may have
a neuroprotective effect on white matter tracts.
Introduction
Abnormalities of cerebral white matter have been reported in
schizophrenia1-4. However, whether those changes are mainly due to
the disorder or are secondarily to antipsychotic treatment remains unclear, as
is the issue of whether they are progressive. Separating influences of these
two mechanisms remains challenging because nearly all patients are
appropriately treated following diagnosis, and antipsychotic drugs have robust
effects on brain anatomy5-7. Comparing never-treated and
antipsychotic-treated long term schizophrenia patients could shed light on
white matter changes over the longer term course of illness and whether these
affects are influenced by antipsychotic drugs.Methods
This study was IRB approved and written informed consent was obtained
from each participant. Thirty-one never-treated, long-term schizophrenia
patients with illness duration ranging from 5 to 47 years, 46 illness duration
matched schizophrenia patients who had received long-term
antipsychotic-treatment, and 58 healthy controls underwent DTI studies. Routine
DTI preprocessing were performed using FSL software. Then, we use Automatic
Fiber Quantification software to identify 20 white matter tracts (JHU white
matter tractography altas) in individual subjects. Tract profiles for
fractional anisotropy (FA) of white matter tracts were extracted and compared
among groups using two-way (3 groups × 20 regions) ANOVAs. Significant effects were followed
by post-hoc one way ANOVAs comparing groups on each tract separately, and then
pairwise post hoc tests to determine which of the 3 groups differed
significantly using 10000 permutation testing. Linear regression analyses were
used to explore the potential relationship between FA for tracts that showed
significant group differences and age among the three groups.Results
FA significantly differed among the three groups
in 14 of 20 white matter tracts defined in the JHU white-matter template
(P<0.05). Compared to antipsychotic-treated patients, untreated long term
schizophrenia patients displayed significantly reduced FA in bilateral anterior
thalamic radiation, left cingulum-hippocampus pathway, splenium and genu of
corpus callosum, left superior longitudinal fasciculus and left superior
longitudinal fasciculus-temporal part, and greater FA in right uncinate fasciculus
(P<0.05, Figure 1). Furthermore, untreated patients showed an accelerated age-related
reduction of FA in the genu of the corpus callosum relative to both treated
patients and controls (P<0.05, Figure 2).Conclusion
The current study revealed more alteration of
white matter microstructure in long-term never-treated schizophrenia patients
than chronically treated patients of similar illness duration. In the genu of
the corpus callosum, in which fibers connect left and right frontal cortex,
there was an accelerated age-related reduction of fiber tract integrity in the
long-term never-treated chronic schizophrenia patients not seen in treated
group. These findings provide insight into disease-related white matter
deficits in the years after illness onset in schizophrenia, and suggest that
long-term antipsychotic treatment may have a neuroprotective effect on white
matter tracts over the longer-term course of illness.
Acknowledgements
This
study was supported by the National Natural Science Foundation (grant numbers
81621003, 81671664 and 81371527), National Youth Top-notch Talent Support
Program of China and the Program for Changjiang Scholars and Innovative
Research Team in University (PCSIRT, IRT1272) of China.References
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