Lei Li1, Xinyu Hu1, Du Lei1, Xiaoqi Huang1, and Qiyong Gong1
1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of
Synopsis
The current
study used voxel-based morphometry (VBM)-diffeomorphic anatomical registration
through exponentiated lie algebra (DARTEL) algorithm to investigate the gray
matter abnormalities in drug-naïve first-episode pediatric patients with posttraumatic
stress disorder (PTSD) using high resolution structural MRI. Meanwhile, we
investigated the association between altered neural correlates and symptom
severity as measured by clinician-administered PTSD scale (CAPS) and PTSD
checklist (PCL) scores with the age as a covariate. The current study provided
the preliminary evidence that the intrinsic abnormalities of neural correlates in
pediatric PTSD patients were mainly in fear circuit and default mode network.PURPOSE
Posttraumatic stress disorder (PTSD) is a trauma- or
stressor-related disorder that is characterized by four clusters of symptoms:
reexperience, hyperarousal, avoidance and negative cognition and mood. Though
previous meta-analysis has indentified decreased gray matter volume (GMV) in
medial prefrontal cortex, left hippocampus, left middle temporal gyrus and
right superior frontal gyrus in adult PTSD patients compared with traumatic
exposed controls (TEC) [1], little is known regarding of pediatric PTSD
patients. The purpose of this study is to investigate brain structural
differences between drug-naïve
first episode pediatric PTSD patients and TEC
using voxel-based morphometry (VBM)-diffeomorphic anatomical registration
through exponentiated lie algebra (DARTEL) algorithm, and evaluate the
relationship between altered cerebral GMV and symptom severity.
METHODS
High-resolution 3-Dimensional
T1WI images were obtained from right-handed earthquake survivors, including 28
drug-naïve first episode pediatric PTSD patients and 26 age- and gender-matched
TEC within 7-15 months after the earthquake. All images were
preprocessed with VBM-DARTEL algorithm using SPM8
software running in Matlab 2012b. The GMV maps were compared between PTSD patients and TEC
by using the voxel-based two-sample t-test in SPM8 with the age as a covariate.
Partial pearson correlation analyses were performed to identify the
association between altered neural correlates and symptom severity as measured by
clinician-administered PTSD scale (CAPS) and PTSD checklist (PCL) scores with the age as a covariate.
RESULTS
Compared to TEC, pediatric PTSD patients showed GMV reductions in
the left inferior frontal gyrus (IFG), left precuneus, left supplementary motor
area (SMA), and bilateral cerebellum (P <0.05, AlphaSim corrected ) (Fig.1).
Correlation analysis showed that GMV of the left precuneus, SMA was positively
correlated with CAPS scores in PTSD patients group, respectively (Fig. 2 A
& B). In addition, GMV of the left SMA was positively correlated with PCL
scores in PTSD group (Fig. 2 C).
DISCUSSION
Pediatric PTSD showed reduced GMV in fear regulatory areas including
the left IFG, left precuneus and left SMA. These regions are important in the
process of fear extinction and attention control. Interestingly, positive
correlations were identified between the GMV of the left precuneus, left SMA
and the severity of PTSD symptoms. We speculated this phenomenon may indicate a
compensatory mechanism that a greater need for the recruitment of regions
implicated in top down attention. This is consistent with a previous PTSD study
reported greater blood oxygenation level dependent (BOLD) signals in the
dorsomedial frontal cortex in response to emotional relative to neutral stimuli
[2]. The precuneus is a core node in the default mode network
(DMN) and disrupted nodal properties of the functional connectome in the DMN were
reported in a recent graph theoretic study in PTSD children [3]. Reduced
bilateral cerebellar volume was not reported in previous neuroinaging
researches employing adult patients with PTSD. We suggested the abnormalities
in cerebellum may be specific in pediatric PTSD, and this notion is supported by
one structural research using region of interest (ROI) approach, which revealed
GMV reduction of cerebellum in pediatric PTSD [4].
CONCLUSION
The current study provided the preliminary evidence of intrinsic
abnormalities of neural correlates at whole-brain level in drug-naïve first
episode pediatric PTSD patients were mainly in fear circuit and DMN. Besides, our
study highlighted reductions of GMV in the cerebellum might be associated with pathophysiology
in youths with PTSD. The positive correlation between GMV abnormalities and
symptom severity suggests that VBM-DARTEL may be of clinical value in measuring
and following disability in pediatric PTSD patients.
Acknowledgements
This study was supported by the National
Natural Science Foundation (Grant No. 81171488,
81227002, and 81220108013), the National Key Technologies Research
and Development Program of China (Program No. 2012BAI01B03) and Program for Changjiang Scholars and
Innovative Research Team in University (PCSIRT, Grant No. IRT1272) of China.
Dr. Qiyong Gong would like to acknowledge his Visiting Adjunct Professor
appointment in the Department of Psychiatry at the Yale School of Medicine,
Yale University, USA.
The authors reported no biomedical financial
interests or potential conflicts of interest
References
[1] Li L, et.al.
(2014) Neurosci Biobehav Rev. 43: 163-172.
[2] White SF, et.al. (2014) Neuroimage Clin. 7: 19-27.
[3] Suo X, et al. (2015)
Hum Brain Mapp. 36: 3677-3686.
[4] Carrion V, et al. (2009) Psychiatry Res. 172: 226-234.