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Two-dimensional neuro MR spectroscopy to detect neurochemical changes in Post-traumatic stress disorder

Article: Post-traumatic stress disorder affects fucose-α(1–2)-glycans in the human brain: preliminary findings of neuro deregulation using in vivo two-dimensional neuro MR spectroscopy

Transl Psychiatry. 2019; 9: 27.

Published online 2019 Jan 18.

doi: 10.1038/s41398-018-0365-6

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338732/

 

Authors: Scott Quadrelli,1,2,3,4 Nathan Tosh,1,3 Aaron Urquhart,1 Katie Trickey,1 Rosanna Tremewan,1 Graham Galloway,1 Lisa Rich,1 Rodney Lea,3 Peter Malycha,1 and Carolyn Mountford1,2

Affiliations:

  1. Translational Research Institute, Woolloongabba, QLD 4024 Australia
  2. Center for MR in Health, University of Newcastle, Newcastle, NSW 2308 Australia
  3. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4000 Australia
  4. Radiology Department, Princess Alexandra Hospital, Woolloongabba, QLD 4024 Australia

Funders:

This study was funded by the Department of Defence of Australia and Department of Defence USA under the MOU and task plan PP-3664-9 concerning combating terrorism research and development and USA Departments of Defence; and the Advance Queensland funding initiative to establish The Translational Research Institute (TRI) Innovation and Translation Centre (IAT Centre) in co-operation with Siemens Healthcare.

Aim:

Post-traumatic stress disorder is prevalent in members of the front line and defence force with 8.3% vs general population. There is an alarming statistics report of 10 times more suicide attempts compared to the general public from a 4000 first responders survey.  Currently the condition is diagnosed with psychological evaluation, the aim of the this study is to present an objective evaluation of neurochemistry using 2D LCOSY (two-dimensional In vivo localized correlated spectroscopy) protocol.

Terminology/ Abbreviations:

  • Post-traumatic stress disorder (PTSD)- failure to recovery from traumatic event experiences
  • COSY- COrrelated SpectroscopY
  • 2D LCOSY(two-dimensional In vivo localized correlated spectroscopy)- In vivo localized correlated spectroscopy (L-COSY) of the human brain (posterior cingulate gyrus)
  • PCG – posterior cingulate gyrus is part of the posteromedial cortex and metabolically active region
  • MRS-Article: Post-traumatic stress disorder affects fucose-α(1–2)-glycans in the human brain: preliminary findings of neuro deregulation using in vivo two-dimensional neuro MR spectroscopyTransl Psychiatry. 2019; 9: 27.Published online 2019 Jan 18.doi: 10.1038/s41398-018-0365-6

    PMCID: PMC6338732

    PMID: 30659168

     

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338732/

     

    Authors: Scott Quadrelli,1,2,3,4 Nathan Tosh,1,3 Aaron Urquhart,1 Katie Trickey,1 Rosanna Tremewan,1 Graham Galloway,1 Lisa Rich,1 Rodney Lea,3 Peter Malycha,1 and Carolyn Mountford1,2

     

    Affiliations:

    1. Translational Research Institute, Woolloongabba, QLD 4024 Australia
    2. Center for MR in Health, University of Newcastle, Newcastle, NSW 2308 Australia
    3. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4000 Australia
    4. Radiology Department, Princess Alexandra Hospital, Woolloongabba, QLD 4024 Australia

    Funders:

    This study was funded by the Department of Defence of Australia and Department of Defence USA under the MOU and task plan PP-3664-9 concerning combating terrorism research and development and USA Departments of Defence; and the Advance Queensland funding initiative to establish The Translational Research Institute (TRI) Innovation and Translation Centre (IAT Centre) in co-operation with Siemens Healthcare.

    Aim:

    Post-traumatic stress disorder is prevalent in members of the front line and defence force with 8.3% vs general population. There is an alarming statistics report of 10 times more suicide attempts compared to the general public from a 4000 first responders survey.  Currently the condition is diagnosed with psychological evaluation, the aim of the this study is to present an objective evaluation of neurochemistry using 2D LCOSY (two-dimensional In vivo localized correlated spectroscopy) protocol.

    Terminology/ Abbreviations:

    • Post-traumatic stress disorder (PTSD)- failure to recovery from traumatic event experiences
    • COSY- COrrelated SpectroscopY
    • 2D LCOSY(two-dimensional In vivo localized correlated spectroscopy)- In vivo localized correlated spectroscopy (L-COSY) of the human brain (posterior cingulate gyrus)
    • PCG – posterior cingulate gyrus is part of the posteromedial cortex and metabolically active region
    • MRS- Neuro magnetic resonance spectroscopy

    Method:

    Collection of samples

    Ethics approval from obtained from the Queensland Metro North and Metro South Human Ethics Committees, the Hunter New England Area Health Ethics, the Australian Defence Health Research Ethics Committee. All collection was made after consent was given by the participants. 20 participants were selected, 10 with PTSD and 10 healthy controls. The two groups were matched based on age, gender and level of education.

    The Criteria for selection is listed below

    For the PTSD Precipitants  

    • Aged between 18 and 65 years.
    • Diagnosed with PTSD according to the DSM-V using the Clinician-Administered PTSD scale (CAPS)27
    • With no current or life-time substance use disorder
    • No current or past history of schizophrenia, bipolar or other psychotic disorder; major head injury,
    • No current or past history of neurological disease
    • No current pregnancy or any other contraindication to MRI scanning.

    For healthy control participants

    • aged between 18 and 65 years
    • no current DSM-V Axis I disorder, as assessed by the Structured Clinical Interview for DSM-V (SCID)28
    • With no history of a mood or anxiety disorder, major head injury
    • No current or past history of neurological disease
    • No current pregnancy or any other contraindication to MRI scanning.

     

    The following testing was undertaken on participants:

    • A Clinical interviews by clinical psychologist
    • A web-based neuro cognitive assessment
    • Magnetic resonance imaging and spectroscopy

    The following analytic information was collected

    • Structural imaging where three-plane localizer image used for MRS voxel placement and whole-brain morphometry.
    • Localized COSY 2D MR spectroscopy- In vivo localized correlated spectroscopy (L-COSY) of the human brain (posterior cingulate gyrus)

    The data from COSY were evaluated and statistical analysis were performed.

    Results:

    The statistically significant neurochemical changes comparing PTSD cohort vs healthy age-matched cohort from posterior cingulate cortex identified with 2D L-COSY were:

    • 12% IMI-1 imidazole
    • 31% fucose region , free substrate fucose and fucosylated glycans
    • 48% Fuc IV- fucosylated glycans
    • 41% Fuc VI- fucosylated glycans
    • 5% the lipid cross-peak B [ HC=CH–CH2–CH2–CH3 ] of lipid fatty acyl chain

    A positive correlation of clinical symptoms of IMI-1 levels in the PCG and severity was also reported.

    Conclusion:

    The ability to use 2D MR to identify statistically significant neurochemical changes is a new opportunity to monitor and observe the effect of altered neurochemistry in PTSD. All the changes can be further investigated, one of which is the two fucose-α(1–2)-glycans ( 48% Fuc IV and 41% Fuc VI) which have been previously been implicated in neuronal development, learning and memory. This research highlights the importance of addressing metal health not only for our local first responders (paramedic, police etc) but also high-risk defence force personal.

    Relevance:

    This pilot study shows great promise in understanding the neurochemical changes using human participants and utilising existing MR technology with many different layers and new protocols. The results of the study have allowed the researchers to hypothesis that the COSY method maybe used to monitor the interaction and communication between nerve cells at the level of atoms and molecules. This can potentially be part of diagnosis and treatment of PTSD in the future.

    HRA Comment:

    Mental health conditions are become more and more prevalent in our community. We commend development to better understand the long-time neurochemical changes through existing technology and advancements of human-relevant research.

Method:

Collection of samples

Ethics approval from obtained from the Queensland Metro North and Metro South Human Ethics Committees, the Hunter New England Area Health Ethics, the Australian Defence Health Research Ethics Committee. All collection was made after consent was given by the participants. 20 participants were selected, 10 with PTSD and 10 healthy controls. The two groups were matched based on age, gender and level of education.

The Criteria for selection is listed below

For the PTSD Precipitants  

  • Aged between 18 and 65 years.
  • Diagnosed with PTSD according to the DSM-V using the Clinician-Administered PTSD scale (CAPS)27
  • With no current or life-time substance use disorder
  • No current or past history of schizophrenia, bipolar or other psychotic disorder; major head injury,
  • No current or past history of neurological disease
  • No current pregnancy or any other contraindication to MRI scanning.

For healthy control participants

  • aged between 18 and 65 years
  • no current DSM-V Axis I disorder, as assessed by the Structured Clinical Interview for DSM-V (SCID)28
  • With no history of a mood or anxiety disorder, major head injury
  • No current or past history of neurological disease
  • No current pregnancy or any other contraindication to MRI scanning.

The following testing was undertaken on participants:

  • A Clinical interviews by clinical psychologist
  • A web-based neuro cognitive assessment
  • Magnetic resonance imaging and spectroscopy

The following analytic information was collected

  • Structural imaging where three-plane localizer image used for MRS voxel placement and whole-brain morphometry.
  • Localized COSY 2D MR spectroscopy- In vivo localized correlated spectroscopy (L-COSY) of the human brain (posterior cingulate gyrus)

The data from COSY were evaluated and statistical analysis were performed.

Results:

The statistically significant neurochemical changes comparing PTSD cohort vs healthy age-matched cohort from posterior cingulate cortex identified with 2D L-COSY were:

  • 12% IMI-1 imidazole
  • 31% fucose region , free substrate fucose and fucosylated glycans
  • 48% Fuc IV- fucosylated glycans
  • 41% Fuc VI- fucosylated glycans
  • 5% the lipid cross-peak B [ HC=CH–CH2–CH2–CH3 ] of lipid fatty acyl chain

A positive correlation of clinical symptoms of IMI-1 levels in the PCG and severity was also reported.

Conclusion:

The ability to use 2D MR to identify statistically significant neurochemical changes is a new opportunity to monitor and observe the effect of altered neurochemistry in PTSD. All the changes can be further investigated, one of which is the two fucose-α(1–2)-glycans ( 48% Fuc IV and 41% Fuc VI) which have been previously been implicated in neuronal development, learning and memory. This research highlights the importance of addressing metal health not only for our local first responders (paramedic, police etc) but also high-risk defence force personal.

Relevance:

This pilot study shows great promise in understanding the neurochemical changes using human participants and utilising existing MR technology with many different layers and new protocols. The results of the study have allowed the researchers to hypothesis that the COSY method maybe used to monitor the interaction and communication between nerve cells at the level of atoms and molecules. This can potentially be part of diagnosis and treatment of PTSD in the future.

HRA Comment:

Mental health conditions are become more and more prevalent in our community. We commend development to better understand the long-time neurochemical changes through existing technology and advancements of human-relevant research.

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