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White Matter Microstructure Is Associated with Serum Neuroactive Steroids and Psychological Functioning.

Lisa F Umminger^1,2, Philine Rojczyk^1,2, Johanna Seitz-Holland¹

¹Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Journal of Neurotrauma

|November 3, 2022

Summary

Military service members with comorbid PTSD and mild traumatic brain injury (mTBI) show altered neurosteroid allopregnanolone (ALLO) levels, impacting white matter integrity and psychological function. This suggests neurosteroid regulation could be key for brain health recovery.

Keywords:

diffusion tensor imaging mild traumatic brain injury military service members neuroactive steroids post-traumatic stress disorder psychological functioning

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Area of Science:

Neuroscience
Psychiatry
Military Medicine

Background:

Military service members face elevated risks for mental health conditions.
Comorbidity with mild traumatic brain injury (mTBI) is frequent, with overlapping symptoms suggesting shared underlying mechanisms.
Neuroactive steroids, like allopregnanolone (ALLO), are integral to the stress-response system and brain function.

Purpose of the Study:

To investigate the relationship between white matter microstructure, psychological functioning, and serum neurosteroid levels in military personnel.
To explore how mild traumatic brain injury (mTBI) and comorbid post-traumatic stress disorder (PTSD) influence these associations.
To identify potential shared pathophysiological pathways for mental health issues in service members.

Main Methods:

Acquired diffusion-weighted brain imaging from 163 participants (military and civilian).
Extracted free-water-corrected fractional anisotropy (FA_T) to assess white matter microstructure.
Utilized regression and moderation models to analyze associations between serum neurosteroid levels (ALLO, PREGNE), FA_T, and psychological functioning, considering mTBI and PTSD+mTBI comorbidity.

Main Results:

Serum allopregnanolone (ALLO) levels were significantly associated with whole-brain white matter FA_T.
This ALLO-FA_T association was significantly modulated by the comorbidity of PTSD and mTBI.
Lower FA_T, indicative of white matter changes, correlated with poorer psychological functioning.

Conclusions:

Neurosteroid dysregulation may represent a common pathophysiological mechanism contributing to mental health challenges in military service members.
The comorbidity of PTSD and mTBI might overwhelm the brain's stress response compensatory mechanisms.
Targeting neurosteroid regulation warrants further investigation as a potential therapeutic strategy for improving brain health and psychological outcomes.