Mild traumatic brain injury impacts associations between limbic system microstructure and post-traumatic stress disorder symptomatology.


Journal

NeuroImage. Clinical
ISSN: 2213-1582
Titre abrégé: Neuroimage Clin
Pays: Netherlands
ID NLM: 101597070

Informations de publication

Date de publication:
2020
Historique:
received: 17 05 2019
revised: 16 01 2020
accepted: 19 01 2020
pubmed: 20 2 2020
medline: 27 3 2021
entrez: 20 2 2020
Statut: ppublish

Résumé

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that afflicts many individuals, yet the neuropathological mechanisms that contribute to this disorder remain to be fully determined. Moreover, it is unclear how exposure to mild traumatic brain injury (mTBI), a condition that is often comorbid with PTSD, particularly among military personnel, affects the clinical and neurological presentation of PTSD. To address these issues, the present study explores relationships between PTSD symptom severity and the microstructure of limbic and paralimbic gray matter brain regions, as well as the impact of mTBI comorbidity on these relationships. Structural and diffusion MRI data were acquired from 102 male veterans who were diagnosed with current PTSD. Diffusion data were analyzed with free-water imaging to quantify average CSF-corrected fractional anisotropy (FA) and mean diffusivity (MD) in 18 limbic and paralimbic gray matter regions. Associations between PTSD symptom severity and regional average dMRI measures were examined with repeated measures linear mixed models. Associations were studied separately in veterans with PTSD only, and in veterans with PTSD and a history of military mTBI. Analyses revealed that in the PTSD only cohort, more severe symptoms were associated with higher FA in the right amygdala-hippocampus complex, lower FA in the right cingulate cortex, and lower MD in the left medial orbitofrontal cortex. In the PTSD and mTBI cohort, more severe PTSD symptoms were associated with higher FA bilaterally in the amygdala-hippocampus complex, with higher FA bilaterally in the nucleus accumbens, with lower FA bilaterally in the cingulate cortex, and with higher MD in the right amygdala-hippocampus complex. These findings suggest that the microstructure of limbic and paralimbic brain regions may influence PTSD symptomatology. Further, given the additional associations observed between microstructure and symptom severity in veterans with head trauma, we speculate that mTBI may exacerbate the impact of brain microstructure on PTSD symptoms, especially within regions of the brain known to be vulnerable to chronic stress. A heightened sensitivity to the microstructural environment of the brain could partially explain why individuals with PTSD and mTBI comorbidity experience more severe symptoms and poorer illness prognoses than those without a history of brain injury. The relevance of these microstructural findings to the conceptualization of PTSD as being a disorder of stress-induced neuronal connectivity loss is discussed.

Sections du résumé

BACKGROUND
Post-traumatic stress disorder (PTSD) is a psychiatric disorder that afflicts many individuals, yet the neuropathological mechanisms that contribute to this disorder remain to be fully determined. Moreover, it is unclear how exposure to mild traumatic brain injury (mTBI), a condition that is often comorbid with PTSD, particularly among military personnel, affects the clinical and neurological presentation of PTSD. To address these issues, the present study explores relationships between PTSD symptom severity and the microstructure of limbic and paralimbic gray matter brain regions, as well as the impact of mTBI comorbidity on these relationships.
METHODS
Structural and diffusion MRI data were acquired from 102 male veterans who were diagnosed with current PTSD. Diffusion data were analyzed with free-water imaging to quantify average CSF-corrected fractional anisotropy (FA) and mean diffusivity (MD) in 18 limbic and paralimbic gray matter regions. Associations between PTSD symptom severity and regional average dMRI measures were examined with repeated measures linear mixed models. Associations were studied separately in veterans with PTSD only, and in veterans with PTSD and a history of military mTBI.
RESULTS
Analyses revealed that in the PTSD only cohort, more severe symptoms were associated with higher FA in the right amygdala-hippocampus complex, lower FA in the right cingulate cortex, and lower MD in the left medial orbitofrontal cortex. In the PTSD and mTBI cohort, more severe PTSD symptoms were associated with higher FA bilaterally in the amygdala-hippocampus complex, with higher FA bilaterally in the nucleus accumbens, with lower FA bilaterally in the cingulate cortex, and with higher MD in the right amygdala-hippocampus complex.
CONCLUSIONS
These findings suggest that the microstructure of limbic and paralimbic brain regions may influence PTSD symptomatology. Further, given the additional associations observed between microstructure and symptom severity in veterans with head trauma, we speculate that mTBI may exacerbate the impact of brain microstructure on PTSD symptoms, especially within regions of the brain known to be vulnerable to chronic stress. A heightened sensitivity to the microstructural environment of the brain could partially explain why individuals with PTSD and mTBI comorbidity experience more severe symptoms and poorer illness prognoses than those without a history of brain injury. The relevance of these microstructural findings to the conceptualization of PTSD as being a disorder of stress-induced neuronal connectivity loss is discussed.

Identifiants

pubmed: 32070813
pii: S2213-1582(20)30027-9
doi: 10.1016/j.nicl.2020.102190
pmc: PMC7026283
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

102190

Subventions

Organisme : NIBIB NIH HHS
ID : P41 EB015902
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD090641
Pays : United States

Informations de copyright

Copyright © 2020. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None.

Références

Mult Scler. 2016 Dec;22(14):1804-1811
pubmed: 26945031
Cereb Cortex. 2016 Oct 17;26(11):4381-4391
pubmed: 26405055
Curr Top Behav Neurosci. 2018;38:163-192
pubmed: 29285732
Psychiatry Res. 2012 Aug-Sep;203(2-3):139-45
pubmed: 23021615
PLoS One. 2012;7(11):e48298
pubmed: 23155380
Brain Imaging Behav. 2018 Feb;12(1):54-63
pubmed: 28102528
J Nerv Ment Dis. 1998 Nov;186(11):701-8
pubmed: 9824173
Biol Psychiatry. 2018 Feb 1;83(3):244-253
pubmed: 29217296
Neuroimage. 2018 Nov 15;182:184-206
pubmed: 29588229
Biol Psychiatry. 2009 Dec 15;66(12):1083-90
pubmed: 19640506
Clin Psychol Rev. 2009 Dec;29(8):674-84
pubmed: 19744760
J Trauma Stress. 2005 Dec;18(6):647-56
pubmed: 16382434
Trends Cogn Sci. 2013 Jul;17(7):337-47
pubmed: 23768722
Front Neurol. 2018 Aug 20;9:616
pubmed: 30177905
J Anxiety Disord. 2013 Jan;27(1):33-46
pubmed: 23247200
Brain Inj. 2017;31(5):674-685
pubmed: 28414250
Neuropsychologia. 2008 Sep;46(11):2836-44
pubmed: 18597797
Magn Reson Med. 2009 Sep;62(3):717-30
pubmed: 19623619
Am J Psychiatry. 2010 Jul;167(7):748-51
pubmed: 20595427
PLoS One. 2013 Jul 19;8(7):e69340
pubmed: 23894451
Brain Inj. 2014;28(3):261-70
pubmed: 24568300
Biol Psychiatry. 2013 Jan 1;73(1):70-4
pubmed: 22840760
Transl Psychiatry. 2013 Jun 04;3:e266
pubmed: 23736119
J Clin Psychiatry. 2013 Nov;74(11):1063-70
pubmed: 24330891
Front Neurosci. 2015 Apr 22;9:128
pubmed: 25954146
Neuroimage. 2013 Apr 1;69:87-100
pubmed: 23247190
J Trauma Stress. 2000 Apr;13(2):181-91
pubmed: 10838669
J Trauma Stress. 1999 Jan;12(1):155-65
pubmed: 10027149
Brain Res. 1992 Aug 21;588(2):341-5
pubmed: 1393587
Am J Epidemiol. 2008 Jun 15;167(12):1446-52
pubmed: 18424429
J Affect Disord. 2005 Sep;88(1):79-86
pubmed: 16033700
NMR Biomed. 2019 Apr;32(4):e3841
pubmed: 29193413
Biol Psychiatry. 2015 Aug 1;78(3):210-6
pubmed: 25818631
J Int Neuropsychol Soc. 2009 Nov;15(6):879-87
pubmed: 19703324
AJNR Am J Neuroradiol. 2002 Jun-Jul;23(6):985-8
pubmed: 12063230
Neuropsychobiology. 2006;54(2):120-5
pubmed: 17199097
Cereb Cortex. 2014 Feb;24(2):328-39
pubmed: 23099298
Pediatrics. 2007 Mar;119(3):509-16
pubmed: 17332204
Psychiatry Res Neuroimaging. 2017 Aug 30;266:1-9
pubmed: 28549317
Psychiatry Res Neuroimaging. 2018 Dec 30;282:110-125
pubmed: 30097168
Sci Rep. 2018 Mar 5;8(1):4011
pubmed: 29507311
Am J Psychiatry. 2007 Jan;164(1):150-3
pubmed: 17202557
J Anxiety Disord. 1998 Nov-Dec;12(6):605-12
pubmed: 9879039
Sci Rep. 2016 Sep 21;6:33748
pubmed: 27651030
Behav Brain Res. 2014 Aug 15;270:307-15
pubmed: 24859173
Neuropsychopharmacology. 2017 Jul;42(8):1739-1746
pubmed: 28272497
J Head Trauma Rehabil. 2014 Jan-Feb;29(1):89-98
pubmed: 23535389
J Clin Psychiatry. 2010 Aug;71(8):992-9
pubmed: 20051219
Psychiatry Res. 2013 Dec 30;214(3):260-8
pubmed: 24074963
Neuroscience. 2017 Apr 21;348:180-190
pubmed: 28196657
J Trauma Stress. 2015 Feb;28(1):25-33
pubmed: 25703936
Sci Transl Med. 2013 Jan 16;5(168):168ra7
pubmed: 23325800
Int J Methods Psychiatr Res. 2017 Sep;26(3):
pubmed: 28211592
Neuroscience. 1995 Nov;69(1):89-98
pubmed: 8637636
J Stud Alcohol. 1982 Nov;43(11):1157-70
pubmed: 7182675
Sci Rep. 2015 Mar 11;5:8933
pubmed: 25757374
Psychoneuroendocrinology. 2005 Nov;30(10):953-8
pubmed: 15963650
JAMA Psychiatry. 2014 Feb;71(2):149-57
pubmed: 24337530
Br J Psychiatry. 2002 Aug;181:102-10
pubmed: 12151279
J Head Trauma Rehabil. 2015 Jan-Feb;30(1):E15-25
pubmed: 24590156
Brain Res. 1990 Oct 29;531(1-2):225-31
pubmed: 1705153
Brain Res. 2013 Jan 15;1490:225-32
pubmed: 23122880
Biol Psychiatry. 2008 Mar 15;63(6):550-6
pubmed: 17825801
Neuroimage Clin. 2013 Apr 22;2:601-11
pubmed: 24179811
Trends Cogn Sci. 2011 Feb;15(2):85-93
pubmed: 21167765
Biol Psychiatry. 2013 Jun 15;73(12):1172-9
pubmed: 23726152
Hippocampus. 2005;15(6):798-807
pubmed: 15988763
Hum Brain Mapp. 2015 Mar;36(3):911-22
pubmed: 25366378
Synapse. 2000 May;36(2):85-94
pubmed: 10767055
Neurosci Lett. 2017 May 10;649:147-155
pubmed: 27916636
Am J Psychiatry. 2009 Jul;166(7):768-76
pubmed: 19448186
Brain Stimul. 2012 Jan;5(1):38-43
pubmed: 22264669
Arch Gen Psychiatry. 2012 Nov;69(11):1169-78
pubmed: 23117638
Science. 2010 Aug 20;329(5994):959-64
pubmed: 20724638
Neuroimage. 2018 Sep;178:104-118
pubmed: 29753105
Pers Individ Dif. 2015 Jul;80:107-112
pubmed: 30034067
Arch Phys Med Rehabil. 2009 Jul;90(7):1084-93
pubmed: 19577020
Neuroimage Clin. 2018 Mar 21;18:888-896
pubmed: 29876273
Neurosci Biobehav Rev. 2006;30(7):1004-31
pubmed: 16730374
J Psychiatr Res. 2010 May;44(7):477-85
pubmed: 19942229
J Neuropsychiatry Clin Neurosci. 2017 Summer;29(3):254-259
pubmed: 28121256
Alzheimers Res Ther. 2015 Jul 01;7(1):47
pubmed: 26136857
Trends Cogn Sci. 2000 Jun;4(6):215-222
pubmed: 10827444
Neuroimage. 2002 Oct;17(2):825-41
pubmed: 12377157
PLoS One. 2014 Sep 03;9(9):e103653
pubmed: 25184336
Neuropsychopharmacology. 2012 Nov;37(12):2740-6
pubmed: 22871912
Neuroimage. 2013 Dec;83:1081-7
pubmed: 23921100
Am J Psychiatry. 1997 Aug;154(8):1114-9
pubmed: 9247398
Neuroimage. 2009 Oct 15;48(1):63-72
pubmed: 19573611
Neuroimage Clin. 2017 Nov 21;17:642-649
pubmed: 29204342
Eur Neuropsychopharmacol. 2017 May;27(5):515-525
pubmed: 28279623
Psychiatry Res. 2015 Apr 30;232(1):1-33
pubmed: 25735885
J Abnorm Psychol. 2002 May;111(2):290-301
pubmed: 12003450
Brain. 2011 Aug;134(Pt 8):2248-60
pubmed: 21764818
Behav Ther. 2006 Dec;37(4):364-80
pubmed: 17071214
Hum Brain Mapp. 2014 Aug;35(8):3841-56
pubmed: 24382651
Cereb Cortex. 2007 Nov;17(11):2609-17
pubmed: 17259644
J Neurotrauma. 2017 Sep;34(S1):S53-S61
pubmed: 28486051
Arch Gen Psychiatry. 2010 Mar;67(3):296-303
pubmed: 20194830
J Rehabil Res Dev. 2008;45(3):437-49
pubmed: 18629752
Hippocampus. 2016 Dec;26(12):1618-1632
pubmed: 27657911
Biometrics. 1946 Dec;2(6):110-4
pubmed: 20287815
Nat Neurosci. 2002 Nov;5(11):1242-7
pubmed: 12379862
JAMA Psychiatry. 2014 Jun;71(6):681-8
pubmed: 24740528
Curr Biol. 2010 Aug 10;20(15):1336-44
pubmed: 20637623
Brain. 2015 Aug;138(Pt 8):2278-92
pubmed: 26033970
Brain Inj. 2012;26(3):201-10
pubmed: 22372408
J Psychosoc Nurs Ment Health Serv. 2010 Feb;48(2):22-8
pubmed: 20166653
Am J Psychiatry. 2004 Mar;161(3):515-24
pubmed: 14992978
CNS Spectr. 2017 Aug;22(4):363-372
pubmed: 27989265
PLoS One. 2013 Jun 11;8(6):e66205
pubmed: 23776631
Curr Psychiatry Rep. 2017 Aug 26;19(10):74
pubmed: 28844076
J Trauma Stress. 1999 Oct;12(4):701-7
pubmed: 10646188
Depress Anxiety. 2016 Apr;33(4):300-7
pubmed: 27038411
Cereb Cortex. 2002 Dec;12(12):1237-43
pubmed: 12427675
Neuroimage. 2018 Nov 15;182:259-282
pubmed: 29729390
Hum Brain Mapp. 2013 Nov;34(11):2808-16
pubmed: 22807242
J Anxiety Disord. 2015 Apr;31:98-107
pubmed: 25768399
J Affect Disord. 2015 Sep 01;183:210-20
pubmed: 26025367
J Nerv Ment Dis. 2005 Oct;193(10):658-64
pubmed: 16208161
N Engl J Med. 2008 Jan 31;358(5):453-63
pubmed: 18234750
J Trauma Stress. 1995 Jan;8(1):75-90
pubmed: 7712061
PLoS One. 2017 Jan 23;12(1):e0170564
pubmed: 28114393
Brain. 2014 Jan;137(Pt 1):12-32
pubmed: 23869106
Biol Psychiatry. 2011 Apr 15;69(8):754-61
pubmed: 21292242
Mol Psychiatry. 2013 May;18(5):618-23
pubmed: 22614289
Psychiatry Res. 2009 Dec 30;174(3):210-6
pubmed: 19914045
Nat Neurosci. 2000 Nov;3(11):1149-52
pubmed: 11036273
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1181-8
pubmed: 20600466
Curr Psychiatry Rep. 2017 Nov 8;19(12):104
pubmed: 29116470
Neuroimaging Clin N Am. 2007 Nov;17(4):523-38, ix
pubmed: 17983968
Front Neuroanat. 2015 Jul 23;9:98
pubmed: 26257612
Psychiatry Res. 2013 Sep 30;213(3):193-201
pubmed: 23816189
J Anxiety Disord. 2009 Jan;23(1):27-37
pubmed: 18434083
Front Syst Neurosci. 2010 Oct 15;4:149
pubmed: 21048904

Auteurs

Valerie J Sydnor (VJ)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Sylvain Bouix (S)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Ofer Pasternak (O)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Elisabeth Hartl (E)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Neurology, University Hospital, LMU Munich, Munich, Germany.

Laura Levin-Gleba (L)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, United States.

Benjamin Reid (B)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Yorghos Tripodis (Y)

Boston University School of Public Health, Boston University, Boston, MA, United States.

Jeffrey P Guenette (JP)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

David Kaufmann (D)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian University, Munich, Germany.

Nikos Makris (N)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Center for Morphometric Analysis, Departments of Psychiatry and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Catherine Fortier (C)

Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States.

David H Salat (DH)

Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, United States; Neuroimaging Research for Veterans (NeRVe) Center, VA Boston Healthcare System, Boston, MA, United States.

Yogesh Rathi (Y)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

William P Milberg (WP)

Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, United States.

Regina E McGlinchey (RE)

Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, United States; Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA, United States.

Martha E Shenton (ME)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; VA Boston Healthcare System, Brockton Division, Brockton, MA, United States.

Inga K Koerte (IK)

Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian University, Munich, Germany. Electronic address: ikoerte@bwh.harvard.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH