Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure

Samantha A Wong; Lauren A M Lebois; Timothy D Ely; Sanne J H van Rooij; Steven E Bruce; Vishnu P Murty; Tanja Jovanovic; Stacey L House; Francesca L Beaudoin; Xinming An; Donglin Zeng; Thomas C Neylan; Gari D Clifford; Sarah D Linnstaedt; Laura T Germine; Kenneth A Bollen; Scott L Rauch; John P Haran; Alan B Storrow; Christopher Lewandowski; Paul I Musey Jr; Phyllis L Hendry; Sophia Sheikh; Christopher W Jones; Brittany E Punches; Michael C Kurz; Robert A Swor; Lauren A Hudak; Jose L Pascual; Mark J Seamon; Claire Pearson; David A Peak; Roland C Merchant; Robert M Domeier; Niels K Rathlev; Brian J O'Neil; Paulina Sergot; Leon D Sanchez; Mark W Miller; Robert H Pietrzak; Jutta Joormann; Deanna M Barch; Diego A Pizzagalli; Steven E Harte; James M Elliott; Ronald C Kessler; Karestan C Koenen; Samuel A McLean; Kerry J Ressler; Jennifer S Stevens; Nathaniel G Harnett

doi:10.1038/s41380-023-02012-3

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure

Mol Psychiatry. 2023 Dec;28(12):5140-5149. doi: 10.1038/s41380-023-02012-3. Epub 2023 Mar 17.

Authors

Samantha A Wong¹, Lauren A M Lebois^{1

2}, Timothy D Ely³, Sanne J H van Rooij³, Steven E Bruce⁴, Vishnu P Murty⁵, Tanja Jovanovic⁶, Stacey L House⁷, Francesca L Beaudoin^{8

9}, Xinming An¹⁰, Donglin Zeng¹¹, Thomas C Neylan¹², Gari D Clifford^{13

14}, Sarah D Linnstaedt¹⁰, Laura T Germine^{2

15

16}, Kenneth A Bollen¹⁷, Scott L Rauch^{2

15

18}, John P Haran¹⁹, Alan B Storrow²⁰, Christopher Lewandowski²¹, Paul I Musey Jr²², Phyllis L Hendry²³, Sophia Sheikh²³, Christopher W Jones²⁴, Brittany E Punches^{25

26}, Michael C Kurz^{27

28

29}, Robert A Swor³⁰, Lauren A Hudak³¹, Jose L Pascual^{32

33}, Mark J Seamon^{33

34}, Claire Pearson³⁵, David A Peak³⁶, Roland C Merchant³⁷, Robert M Domeier³⁸, Niels K Rathlev³⁹, Brian J O'Neil⁴⁰, Paulina Sergot⁴¹, Leon D Sanchez^{37

42}, Mark W Miller^{43

44}, Robert H Pietrzak^{45

46}, Jutta Joormann⁴⁷, Deanna M Barch⁴⁸, Diego A Pizzagalli^{1

2}, Steven E Harte^{49

50}, James M Elliott^{51

52

53}, Ronald C Kessler⁵⁴, Karestan C Koenen⁵⁵, Samuel A McLean^{56

57}, Kerry J Ressler^{1

2}, Jennifer S Stevens^#⁵⁸, Nathaniel G Harnett^#^{59

60}

Affiliations

¹ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA.
² Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
³ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁴ Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, USA.
⁵ Department of Psychology, Temple University, Philadelphia, PA, USA.
⁶ Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA.
⁷ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Department of Epidemiology, Brown University, Providence, RI, USA.
⁹ Department of Emergency Medicine, Brown University, Providence, RI, USA.
¹⁰ Institute for Trauma Recovery, Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹¹ Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
¹² Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
¹³ Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.
¹⁴ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹⁵ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁶ The Many Brains Project, Belmont, MA, USA.
¹⁷ Department of Psychology and Neuroscience & Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁸ Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁹ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
²⁰ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, USA.
²² Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
²³ Department of Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
²⁴ Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
²⁵ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA.
²⁶ Ohio State University College of Nursing, Columbus, OH, USA.
²⁷ Department of Emergency Medicine, University of Alabama School of Medicine, Birmingham, AL, USA.
²⁸ Department of Surgery, Division of Acute Care Surgery, University of Alabama School of Medicine, Birmingham, AL, USA.
²⁹ Center for Injury Science, University of Alabama at Birmingham, Birmingham, AL, USA.
³⁰ Department of Emergency Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
³¹ Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
³² Department of Surgery, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
³³ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³⁴ Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, USA.
³⁵ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
³⁶ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
³⁷ Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³⁸ Department of Emergency Medicine, Saint Joseph Mercy Hospital, Ypsilanti, MI, USA.
³⁹ Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, USA.
⁴⁰ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
⁴¹ Department of Emergency Medicine, McGovern Medical School at UTHealth, Houston, TX, USA.
⁴² Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
⁴³ National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA.
⁴⁴ Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
⁴⁵ National Center for PTSD, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA.
⁴⁶ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
⁴⁷ Department of Psychology, Yale University, New Haven, CT, USA.
⁴⁸ Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA.
⁴⁹ Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵⁰ Department of Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵¹ Kolling Institute, University of Sydney, St Leonards, NSW, Australia.
⁵² Faculty of Medicine and Health, University of Sydney, Northern Sydney Local Health District, Camperdown, NSW, Australia.
⁵³ Physical Therapy & Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁵⁴ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
⁵⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁵⁶ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵⁷ Institute for Trauma Recovery, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵⁸ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. [email protected].
⁵⁹ Division of Depression and Anxiety, McLean Hospital, Belmont, MA, USA. [email protected].
⁶⁰ Department of Psychiatry, Harvard Medical School, Boston, MA, USA. [email protected].

^# Contributed equally.

Abstract

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Publication types

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

MeSH terms

Adult
Adult Survivors of Child Abuse* / psychology
Anisotropy
Anxiety
Brain / pathology
Child Abuse* / psychology
Depression
Diffusion Tensor Imaging* / methods
Female
Humans
Internal Capsule* / pathology
Male
Middle Aged
Self Report
Stress Disorders, Post-Traumatic* / physiopathology
Stress Disorders, Post-Traumatic* / psychology
White Matter* / pathology
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding