Synopsis
This lecture will provide a brief review on the Post-Traumatic Stress Disorder （PTSD） in general，and an overview of the
PTSD related brain abnormalities discovered with the use of psychiatric MR,
with particular emphasis on the circuitry impairment as observed from the
circuit- and network-based analysis. Methodological challenges and opportunities will be discussed, along
with the assessment of the clinical usefulness of the research findings using psychiatric MR imaging into the objective diagnosis,
prognostic prediction and treatment evaluation of patients with PTSD.Specialty area
Psychiatric disease
Title of session
Weekend Educational Course: Neuro 2
Speaker Name
Qiyong Gong, M.D., Ph.D. (
qiyonggong@hmrrc.org.cn)
Highlights
1. MR Imaging
markers / "radiological signs" for PTSD provide clinically useful addition to the
currently symptom-based diagnoses.
2. Psychiatric
MR techniques in conjunction with the circuit-based analysis, provide useful tool
to study the disrupted brain circuitry of the PTSD.
3. Discoveries from
the MR imaging of the PTSD are of translational value for the patient care.
TALK TITLE
Psychiatric Disease:
Post-Traumatic Stress Disorder
TARGET AUDIENCE
Psychiatrists, clinical psychologists, neuroradiologists,
neurologists, neuroscientists, MR technologists and other researchers with an
interest in the technical and clinical aspects of psychological and
neuropsychiatric imaging.
OUTCOME/OBJECTIVES
1. Have a basic understanding
of the PTSD, the resilient characteristics in traumatic survivors without PTSD,
and the neurobiological underpinnings in the development of PTSD.
2. Update the most
reported imaging findings for PTSD.
3. Introduce
circuit-based analysis methods, and review the circuitry abnormalities related
to PTSD and the individuals at high risk.
4. Discuss
methodological challenges and opportunities provided by psychiatric MR, and the
potentials for its clinical applications in patient care.
PURPOSE
Post-traumatic
stress disorder (PTSD) is a highly disabling condition that can affect
individuals exposed to traumatic events. PTSD's psychological manifestations
are well characterized, such as the typical symptoms of re-experience,
avoidance, hyperarousal and negative mood and cognition. However, emerging evidence suggest that PTSD
patients also have clinically relevant changes in brain circuits and networks. In
particular, the fear circuit is vitally involved in the development of PTSD. Technically, the development of the multi-modal MRI
allows the quantification of brain tissue at the structural, functional and
molecular levels which allows the identification of the imaging markers for
PTSD. In conjunction with the circuit-based analysis methods, MRI can be utilized
to investigate the circuit abnormalities and it is capable
of giving us further insight into underlying psychopathology of the PTSD.
This lecture will provide an overview of the PTSD related brain abnormalities detected using psychiatric MR imaging,
with particular focus on the circuitry impairment, along with the potential clinical
translation of the research findings.
METHODS
1.Structural
imaging
1.1 Diffusion tensor imaging (DTI),
tractography, tract-based spatial statistics (TBSS), FMRIB Software Library
(FSL)
1.2 Cortical thickness analysis, Freesurfer
1.3 Voxel-based analysis (VBM), diffeomorphic
anatomical registration through exponentiated lie algebra (DARTEL)
2.Functional
imaging
2.1 Functional connectivity (FC)
2.2 Graph theory analysis, small-world
properties, network-based statistics (NBS)
3.Methods
for brain connectivity detection
3.1 Model-driven methods:
cross-correlation analysis, coherence analysis, analysis based on general
linear model (GLM) and Gaussian random field (GRF) theory
3.2 Data-driven methods:
decomposition-based methods, including principal component analysis, singular
value decomposition, and independent component analysis (ICA); clustering
analysis methods, including fuzzy clustering analysis, and hierarchical
clustering analysis
RESULTS
1. Multimodal
psychiatric MR reveals various promising biomarkers:
1.1 Psychiatric imaging and connectome studies based on structural and functional
imaging modalities reveal diagnostic biomarkers and identify potential therapeutic
targets for psychiatric disorders including PTSD.1-5
1.2 Structural
study of grey matter and white matter reveals
differentiated biomarkers for early-onset PTSD and resilient population.6
2. Most relevant circuits have been identified:
2.1 Fear circuit,
including the prefrontal cortex, hippocampus, amydala
● This circuit is implicated in the
processing of threat evaluation, fear condition, fear response and fear
extinction in PTSD.7,8 Studies supported this view with the
observation of decreased gray matter volume in medial prefrontal cortex and
hippocampus in PTSD.9,10
2.2. Prefrontal-limbic-striatal
circuit
● This circuit is essentially implicated in
the high-risk population for development of PTSD. Multi-modal MRI techniques,
including resting-state MRI, three-dimensional T1 -weighted imaging, and DTI, consistently found
prefrontal-limbic-striatal circuit abnormalities in trauma survivors.11-15
2.3.Triple network,
including central executive network (CEN), salience network (SN), default mode
network (DMN)
● Children are more vulnerable to develop
PTSD than adults. There may be different pathological mechanisms involved in pediatric
PTSD.
● Disequilibrium in the triple circuit has
been suggested in the pathophysiology of pediatric PTSD.3, 16
3. Prognostic prediction of individual psychopathology in trauma survivors :
The use of relevance vector regression (RVR) allowed quantitative
prediction of clinical scores of PTSD with statistically significant accuracy based on resting-state
fMRI in prefrontal, parietal, and occipital regions.17
DISCUSSION
1. Application of “radiological signs” (i.e.,
imaging biomarkers) of PTSD allows discrimination of PTSD patients from healthy
controls at the individual level, and also quantitative prediction of clinical
scores in patients with statistically significant accuracy.
2. Circuit and
network abnormalities, including fear circuit, OFC-visual occipital circuit,
prefrontal-limbic-striatal circuit and triple network have been identified in
PTSD and high-risk population.
3. Findings of the Circuit-based
analysis of the brain connectivity provide novel insight into psychopathological
mechanism of the mental disorders.
CONCLUSION
Psychiatric MRI hold the
promise not only to aid the clinical diagnose and therapeutic assessment of the
patient with PTSD, but also help studying the psychopathology of the mental illnesses.
Acknowledgements
The author would like to thank Dr Lei Li from
Huaxi MR Research Center (HMRRC) at West China Hospital of Sichuan University, for
her assistance in the preparation of this presentation. References
1. Gong Q, He Y (2015). Depression, Neuroimaging and
Connectomics: A Selective Overview. Biological Psychiatry, 77 (3), 223-35. [Invited Review]
2. Lei D, Li K, Li L, Chen F, Huang X, Lui S, Li J, Bi
F, Gong Q (2015). Disrupted Functional Brain connectome in Patients with Posttraumatic
stress Disorder. Radiology, 276(3):818-27.
3. Suo X, Lei D, Li K, Chen F, Li F, Li L,
Huang X, Lui S, Li L, Kemp GJ, Gong Q (2015). Disrupted Brain Network Topology in Pediatric Posttraumatic Stress Disorder: A Resting-state fMRI Study. Human Brain
Mapping, 36(9):3677-86.
4. Gong Q, Lui S, Sweeney JA (2016). A Selective Review of Cerebral Abnormalities in Patients with First-episode Schizophrenia Before and After Treatment. American Journal of Psychiatry. In press, online available and highlighted by AJP Podcast (ajp.psychiatryonline.org). [Invited Review]
5. Lui S, Zhou XJ, Sweeney J, Gong QY (2016).
Psychoradiology: The Frontier of Neuroimaging in Psychiatry. Radiology, In press. [Invited Review]
6. Li S, Huang X, Li L, Du F, Li J, Bi F,
Lui S, Turner J, Sweeney J, Gong Q (2016). Posttraumatic Stress Disorder: Structural
Characterization with 3-TMR Imaging, Radiology, In press.
7. Keding
TJ, Herringa RJ (2015). Abnormal Structure of Fear Circuitry in Pediatric Post-traumatic Stress Disorder. Neuropsychopharmacology, 40(3): 537-45.
8.
Rodrigues SM, LeDoux JE, Sapolsky RM (2009). The Influence of Stress Hormones on Fear Circuitry. Annual Review of Neuroscience, 32: 289-313.
9. Li L, Lei D, Li L, Huang X, Suo X, Xiao F, Kuang W, Li J, Bi F, Lui S, Kemp GJ, Sweeney
JA, Gong Q (2016). White Matter Abnormalities in Post-traumatic Stress Disorder
Following a Specific Traumatic Event. EbioMedicine, In press, online available.
10. Li L,
Wu M, Liao Y, Ouyang L, Du M, Lei D, Chen L,
Yao L, Huang X, Gong Q (2014). Grey Matter Reduction Associated with Posttraumatic Stress Disorder and Traumatic Stress. Neuroscience and Biobehavioral Reviews, 43: 163-72.
11. Lui S,
Huang X, Chen L, Tang H, Zhang T, Li X, Li D, Kuang W, Chan RC, Mechelli A, Sweeney
JA, Gong Q (2009). High-field MRI Reveals An Acute Impact on Brain Function in Survivors
of The Magnitude 8.0 Earthquake in China. Proceedings of the National Academy
of Sciences of the United States of America (PNAS), 106(36): 15412-7.
12. Lui S,
Chen L, Yao L, Xiao Y, Wu QZ, Zhang JR, Huang X, Zhang W, Wang YQ, Chen HF, Chan
RC, Sweeney JA, Gong Q (2013). Brain Structural Plasticity in Survivors of A Major Earthquake. Journal of Psychiatry & Neuroscience, 38(6):
381-7.
13. Chen L, Lui S, Wu Q, Zhang W, Zhou D, Chen H,
Huang X, Kuang W, Chan R, Mechelli A ,Gong Q (2013). Impact of Acute Stress on Human Brain Microstructure: An MR Diffusion Study of Earthquake Survivors. Human
brain mapping, 34(2): 367-73.
14. Du MY, Liao W, Lui S, Huang XQ, Li F, Kuang
WH, Li J, Chen HF, Kendrick KM, Gong Q (2015). Altered Functional Connectivity in The Brain Default-mode Network of Earthquake Survivors Persists after 2 Years Despite Recovery from Anxiety Symptoms. Social Cognitive and Affective Neuroscience, 10(11):1497-505.
15. Long J, Huang X, Liao Y, Hu X, Hu J, Lui S, Zhang
R, Li Y, Gong Q (2014). Prediction of Post-earthquake Depressive and Anxiety Symptoms:
a Longitudinal Resting-state fMRI Study. Scientific Reports, 4: 6423.
16. Lei D,
Li L, Suo X, Huang X, Lui S, Li J, Bi F , Kemp GJ , Gong Q (2015). Microstructural Abnormalities in Children with Post-traumatic Stress Disorder: A Diffusion Tensor Imaging Study at 3.0 T. Scientific Reports, 5: 8933.
17. Gong Q, Li L, Du M,
Pettersson-Yeo W, Crossley N, Yang X, Li J, Huang X, Mechelli A (2014). Quantitative Prediction of Individual Psychopathology in Trauma Survivors using Resting-state FMRI. Neuropsychopharmacology, 39(3): 681-7.