Research reportAssociation of abnormal white matter integrity in the acute phase of motor vehicle accidents with post-traumatic stress disorder
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.
References (60)
- et al.
MR diffusion tensor spectroscopy and imaging
Biophys. J.
(1994) - et al.
White matter abnormalities in Gulf War veterans with posttraumatic stress disorder: a pilot study
Psychoneuroendocrinology
(2015) - et al.
Altered emotional interference processing in the amygdala and insula in women with post-traumatic stress disorder
NeuroImage Clin.
(2013) - et al.
Predictive factors of chronic post-traumatic stress disorder 6 months after a road traffic accident
Accid. Anal. Prev.
(2011) - et al.
Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury
NeuroImage
(2012) - et al.
A systematic review of predictors of posttraumatic stress disorder (PTSD) for adult road traffic crash survivors
Injury
(2013) - et al.
Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification
Neuroimage
(2008) - et al.
Corpus callosum in maltreated children with posttraumatic stress disorder: a diffusion tensor imaging study
Psychiatry Res.: Neuroimaging
(2008) - et al.
The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI
Eur. Psychiatry
(1997) - et al.
Reduced white matter integrity in the cingulum and anterior corona radiata in posttraumatic stress disorder in male combat veterans: a diffusion tensor imaging study
Psychiatry Res.: Neuroimaging
(2013)
Patterns of altered cortical perfusion and diminished subcortical integrity in posttraumatic stress disorder: an MRI study
Neuroimage
The effects of temporal unpredictability in anticipation of negative events in combat veterans with PTSD
J. Affect. Disord.
Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data
Neuroimage
Advances in functional and structural MR image analysis and implementation as FSL
Neuroimage
Major depressive and post-traumatic stress disorder comorbidity in female victims of intimate partner violence
J. Affect. Disord.
From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders
Neurobiol. Learn. Mem.
Permutation inference for the general linear model
Neuroimage
Altered resting-state functional connectivity of basolateral and centromedial amygdala complexes in posttraumatic stress disorder
Neuropsychopharmacology
Assessing acute stress disorder: psychometric properties of a structured clinical interview
Psychol. Assess.
Statistical Power Analysis for the Behavioral Sciences
A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion
J. Neurotrauma
White matter integrity in highly traumatized adults with and without post-traumatic stress disorder
Neuropsychopharmacology
Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing
PLoS ONE
Early intervention for preventing posttraumatic stress disorder: an Internet-based virtual reality treatment
Eur. J. Psychotraumatology
Psychometric properties of the life events checklist
Assessment
The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD–a monozygotic twin study
Biol. Mood Anxiety Disord.
Mild traumatic brain injury in US soldiers returning from Iraq
New. Engl. J. Med.
Abnormalities in whole-brain functional connectivity observed in treatment-naive post-traumatic stress disorder patients following an earthquake
Psychol. Med.
Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex
Proc. Natl. Acad. Sci. United States Am.
Cited by (32)
Persistence of post-traumatic stress disorder in Chinese Shidu parents is associated with combined gray and white matter abnormalities
2023, Psychiatry Research - NeuroimagingCorrelates of dangerous driving among late adolescents: Evidence from American and Czech males
2023, Personality and Individual DifferencesFunctional neuro-anatomy of social cognition in posttraumatic stress disorder: A systematic review
2022, Psychiatry ResearchCitation Excerpt :DTI study (Koch et al., 2017) reported reduced interconnectivity between amygdala and vmPFC, in accordance with PTSD neuro-anatomical dysfunction model: the emotional undermodulation model (Lanius et al., 2010). Some DTI studies have reported decreased white matter tracts in PTSD (Hanson et al., 2015; Hu et al., 2016). Fiber tracts reduced integrity between limbic structures and PFC is a plausible explanation for PFC less control, and more particularly vmPFC, dedicated to behavioural/emotional control, over limbic structures such amygdala.
Racial Discrimination and White Matter Microstructure in Trauma-Exposed Black Women
2022, Biological PsychiatryCitation Excerpt :The CC is the major set of interhemispheric projections of the brain; the morphology of this tract is affected by early-life adversity and PTSD more generally (45,46); CC decrements were observed in a mega-analysis of PTSD studies (25). Further, the SLF is a major frontoparietal connection that supports a range of cognitive and emotional functions including attention and executive functioning, language, and social cognition (47) and is implicated in trauma-related responses/PTSD (24,48,49). Finally, the CB is a major association tract connecting parahippocampal regions with the parietal cortex and prefrontal cortex.
Acute Posttraumatic Symptoms Are Associated With Multimodal Neuroimaging Structural Covariance Patterns: A Possible Role for the Neural Substrates of Visual Processing in Posttraumatic Stress Disorder
2022, Biological Psychiatry: Cognitive Neuroscience and NeuroimagingTreatment outcome of posttraumatic stress disorder: A white matter tract analysis
2021, Journal of Anxiety Disorders
- 1
These authors contributed equally to the study.