Alterations of neural correlates in drug-naïve first episode pediatric patients with posttraumatic stress disorder: An optimized voxel-based morphometry study
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.

Figures

Fig. 1: Gray matter reductions in pediatric PTSD patients compared with controls.

Fig. 2: Correlations of gray matter volume in the left precuneus with CAPS scores (A), left SMA with CAPS scores (B), left SMA with PCL scores (C).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
4153