Elsevier

Journal of Affective Disorders

Volume 190, 15 January 2016, Pages 714-722
Journal of Affective Disorders

Research report
Association of abnormal white matter integrity in the acute phase of motor vehicle accidents with post-traumatic stress disorder

https://doi.org/10.1016/j.jad.2015.09.044Get rights and content

Abstract

Background

A small portion of the Motor vehicle accidents (MVA) survivors would develop post-traumatic stress disorder (PTSD), which would cause substantial social function loss. How to identify those high-risk MVA survivors in the acute phase of the trauma is the first step to prevent the onset of PTSD. In the present study, we studied white matter integrity of subjects post to MVA by diffusional tensor imaging (DTI).

Methods

To investigate whether the integrity of the white matter was impaired in the acute phase of the MVA among survivors who later develop PTSD and whether it could predict the severity of PTSD while being diagnosed. MVA Survivors were recruited to get trauma-specific clinical assessments and received DTI scan within 2 days from the MVA. These survivors were divided into 2 groups, PTSD group and trauma control (TC) group based on the clinical follow-up interview. Tract-Based Spatial Statistics (TBSS) was carried out to investigate difference in white matter integrity between 2 groups within DTI parameter maps. White matter integrity was measured by using fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radical diffusivity (RD).

Results

Compared with TC group, PTSD group showed lower FA value in multiple regions of both hemispheres, mainly involving anterior thalamic radiation, cortico-spinal tract, forceps minor, uncinate, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, cingulum and superior longitudinal fasciculus. Increased RD was also detected in PTSD group in the posterior part of right hemisphere, involving forceps major, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, cingulum, hippocampus and superior longitudinal fasciculus. The baseline FA and RD values correlated with Clinician-Administered PTSD Scale scores at clinical follow up.

Conclusion

MVA survivors who later developed PTSD had more abnormalities in white matter integrity in the acute phase than those non-PTSD MVA survivors. Imaging markers of white matter integrity might be helpful in early identification of MVA survivors at high risk of PTSD.

Limitations

Larger sample size in our extensive study is needed to confer a robust inference and image data at follow up are needed to observe the longitudinal changes of white matter integrity.

Introduction

Motor vehicle accident (MVA), as a typical traumatic event in life, can greatly damage survivors' physical health. It is estimated that about 1.24 million people die of traffic accidents and 20–50 million are injured every year across the world (WHO, 2013). Previous works have proven that MVA survivors could suffer from various psychiatry diseases in the courses of their recovery. Researches focusing on the epidemiology of mental illnesses following MVA have become popular since the beginning of this century (Chossegros et al., 2011, Mirza et al., 1998, Murray et al., 2002). Among these mental illnesses, post-traumatic stress disorder (PTSD) is the leading and most harmful one. Compared with other traumatic events, the prevalence of MVA related PTSD is quite high among the MVA survivors. It was reported that approximately 23–25% MVA survivors would be diagnosed of PTSD within 3 to 6 months post to accidents (Heron-Delaney et al., 2013). The high prevalence of MVA-related PTSD is partially due to the fact that victims’ heads can easily get stricken in the accidents, resulting in minutes of loss of consciousness (LOC) which indicates mild traumatic brain injury (mTBI) and could further increase the prevalence rate of PTSD (Roitman et al., 2013).

Although the prevalence of PTSD is high in MVA survivors, it is not necessary for every survivor to develop the disease eventually. Thus, it is critical to identify those subjects with high PTSD risks at the acute phase of MVA. The identification may guide offering medical aids to the high-risk subjects, as a previous study reported that early detection and intervention in the acute phase of traumatic events could decrease the prevalence rate of PTSD in trauma victims (Freedman et al., 2015).

Recently, magnetic resonance imaging (MRI) has emerged as a reliable measure to yield the neurological biomarkers in PTSD patients, which can help identify high-risk PTSD subjects from trauma victims in the acute phase. That is, the characteristics of PTSD should be identified from MRI data, in order to screen potential PTSD patients. Several works in literatures have reported the features of the dysfunctional brains in PTSD patients with general traumas. For example, the frontal–limbic dysfunction model was used for describing PTSD (VanElzakker et al., 2014). Amygdala (Felmingham et al., 2014), insula (Nardo et al., 2011, Simmons et al., 2013), anterior cingulate cortex (ACC) (Moser et al., 2015), and hippocampus (Wang et al., 2010) , which were involved in the loop, were addressed due to their important roles in the prevalence of PTSD, respectively. It is known that the dysfunctional frontal–limbic loop is responsible for emotional regulation failure, which confers the hyper-arousal symptoms of PTSD. However, the stand-alone failure of only this loop cannot explain other symptom clusters (e.g. re-experiencing or avoidance), as well as several domains of cognition deficiency (Qureshi et al., 2011). Further, a large-scale network of brain regions, which consist of several neural loops, are disturbed in PTSD patients due to injuries that hamper normal integrity of white matter (Tursich et al., 2015). Meanwhile, functional MRI (fMRI) is also applied widely in PTSD studies as the technique providing indirect measure for the connectivity among cortices. Altered functional connectivity was reported between medial pre-frontal cortex (mPFC) and amygdala (Jin et al., 2014), between basolateral and centromedial amygdala complexes (Brown et al., 2014), and among the key nodes of the default mode network (DMN) (Sripada et al., 2012). In our previous work, abnormal functional connectivity was detected among several DMN regions within two days after MVA from those subjects who later developed PTSD (Wang et al., 2012). In summary, several neurological loops, e.g. a large network of neural nodes, may be altered in PTSD patients.

The abnormal functional connectivity could be explained by injured white matter fibers (Bruce et al., 2013), which is typically observed by diffusion tensor imaging (DTI). In particular, DTI can be used to reveal the injured regions of white matter, by examining the diffusion movement of water molecules within the white matter fiber bundles (Basser et al., 1994). Water molecules tend to diffuse along the axial direction of the white matter fibers, while the diffusion movement, in parallel with the radial direction, is restricted by the compact myelin. The pattern of water diffusion in axons, namely anisotropy, can reflect white matter integrity through several commonly used scalar measures, including mean diffusivity (MD), radical diffusivity (RD), axial diffusivity (AD), and fractional anisotropy (FA). MD measures the general displacement of water molecules and their abilities to penetrate the obstacles. RD measures the abilities of water molecules to move along the perpendicular directions of white matter fibers, thus reflecting the extent of myelin injury. AD measures the extent to which water molecules could move along the axial direction, and thus provides a natural description of the injury of axons. FA, ranging from 0 to 1, reflects myelination and axonal density of the white matter fibers.

Previous researches have already explored the white matter integrity in the subjects with PTSD. On one hand abnormal white matter integrity is observed within the frontal–limbic loop by different researchers focusing on different types of traumas (Fani et al., 2012, Kim et al., 2005, Schuff et al., 2011). Abnormal integrity in cingulum in PTSD is a common finding among different researches, reflecting inefficient communication between the frontal cortex and the limbic lobe. On the other hand, some researchers also described abnormal white matter integrity outside the frontal–limbic loop in PTSD subjects. Increased FA value was observed in the right precuneus and the right parietal sub-gyrus in a cohort of coalmine survivors with PTSD (Zhang et al., 2012). Schuff et al. (2011) found decreased FA value in the precentral gyrus, and the posterior internal capsule in war-related PTSD subjects. In additions, the severity of PTSD symptoms was associated with DTI scalar measures (FA, MD, etc.), which indicated that DTI scalar could be used to assess PTSD illness severity (Bierer et al., 2015).

However, the studies mentioned above were limited by the cross-sectional nature, as subjects were included only when PTSD was diagnosed. In this way, white matter integrity before the onset of PTSD cannot be known. With the DTI data collected around MVA, we have got the chance to probe the white matter integrity before subjects meet the diagnosis criterion of PTSD. In addition, it is interesting to predict the progress of the latent disease. For example, an fMRI study described the resting state functional connectivity between the posterior cingulate cortex and the amygdala, and then predicted future PTSD symptoms (Lanius et al., 2010). In this study, we also tried to explore possible associations between baseline DTI scalar measures and the PTSD severity scores at follow-ups, providing possible screening method for subjects with high risk for PTSD.

By statistical parametric mapping (SPM) and whole brain voxel based analysis (VBA), our group found (1) lower FA in the anterior cingulate cortex, ventromedial prefrontal cortex, temporal lobes, and midbrain; (2) increased MD in vmPFC, for patients within two days after the traumatic events (Sun et al., 2013). In this present work, we further examined our DTI data with Tract-Based Spatial Statistics (TBSS) (Smith et al., 2006). Compared with our previous analysis, TBSS projects the fiber tract representations of individual volumes to a single sample (i.e., the ‘‘mean FA skeleton’’) after non-linear registration. It is shown in the literature that TBSS can improve the statistic power of multi-subject study of DTI data (Smith et al., 2006).

In the present study, all patients underwent the baseline MRI scans within 48 h after they ran into traffic accidents. This study was conducted as an extension to our previous works on PTSD after MVA (Sun et al., 2013, Wang et al., 2012, Zhou et al., 2012), aiming to screen potential PTSD subjects by DTI technique. We further checked the correlation between the white matter integrity at baseline and the PTSD symptom scores acquired at follow-up interviews after MVA. We have two hypotheses in this work: (1) the abnormal integrity of white matter should be detected within the brain, indicating multiple altered neural loops; and (2) baseline imaging data (e.g., FA or RD measured from DTI) should be correlated with the severity of the follow-up PTSD symptoms.

Section snippets

Subjects

A cohort of participants was recruited among MVA survivors, who were admitted to neurosurgical emergency room between 2009 and 2011 and met Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) PTSD criterion A. Participants eligible for our study were all aged 18–60, right handed, with an education over nine years and enrolled in our study within two days after the accidents. Most of these subjects suffered serious somatic injuries or mild head traumas. Head CT

Demographic and clinical features

Details of the demographic and clinical data were shown in Table 1. As expected, there was no statistical significance observed for age, education and ASDI score between the two groups. ASDI score in both groups were much higher than 3. Compared with the trauma control, PDI scores and BDI scores in PTSD group were significantly higher. Significant difference also existed between the 2 groups in CAPS total score.

Diffusion parameters

No significant differences were detected in AD and MD parameter maps. Compared with

Discussions

Our series of studies (Sun et al., 2013, Wang et al., 2012, Zhou et al., 2012), are the first to conduct the MRI based researches on patients in acute phases of MVA. In particular, we collected baseline image data within two days after MVA exposure. To our knowledge, this study is the first to perform TBSS analysis of multiple DTI parameters such as FA, MD, RD and AD maps computed from DTI image acquired in acute phase of MVA.

In accordance with our original hypothesis, abnormal white matter

Conclusion

The findings of our study suggest that a large range of white matter could be injured both by the toxic chemicals induced by the high intense stress or by the direct knock upon victims' heads in MVA. Victims showing symptoms of mTBI following MVA, perhaps yielding a diffuse pattern of white matter injuries, would be at ultra high risk for developing PTSD during the progress of their recovery, whom should be given proper psychological aids by some special experts allocated in emergency room. If

Conflict of interests

No.

Author contributions

H.H analyzed the DTI data, did the statistical analysis and wrote the first manuscript. Y.Z and Q.W provided valuable advices on the protocols, helped the analysis of the DTI data and revised the manuscript. S.S Su and H.H recruited the MVA victims and interviewed them. YMQ and JWG helped recruit the patients and follow up them. ZPX and ZW designed the protocol of the study and acted to supervise the process of the study. All authors approved the final manuscript.

Role of funding sources

The research was supported by grants from the National Natural Science Foundation of China (No.81371486), the Shanghai Rising-Star Program (No.13QA1403200), and the Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared no conflict of interest.

Acknowledgments

The authors thank all participants of this study and all the staffs of emergency rooms of Renji Hospitals for helping recruiting the participants.

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