Abstract
Background
Posttraumatic stress disorder (PTSD) is a debilitating disorder, and there is no current
accurate prediction of who develops it after trauma. Neurobiologically, individuals
with chronic PTSD exhibit aberrant resting-state functional connectivity (rsFC) between
the hippocampus and other brain regions (e.g., amygdala, prefrontal cortex, posterior
cingulate), and these aberrations correlate with severity of illness. Previous small-scale
research (n < 25) has also shown that hippocampal rsFC measured acutely after trauma is predictive
of future severity using a region-of-interest–based approach. While this is a promising
biomarker, to date, no study has used a data-driven approach to test whole-brain hippocampal
FC patterns in forecasting the development of PTSD symptoms.
Methods
A total of 98 adults at risk of PTSD were recruited from the emergency department
after traumatic injury and completed resting-state functional magnetic resonance imaging
(8 min) within 1 month; 6 months later, they completed the Clinician-Administered
PTSD Scale for DSM-5 for assessment of PTSD symptom severity. Whole-brain rsFC values
with bilateral hippocampi were extracted (using CONN) and used in a machine learning
kernel ridge regression analysis (PRoNTo); a k-folds (k = 10) and 70/30 testing versus training split approach were used for cross-validation
(1000 iterations to bootstrap confidence intervals for significance values).
Results
Acute hippocampal rsFC significantly predicted Clinician-Administered PTSD Scale for
DSM-5 scores at 6 months (r = 0.30, p = .006; mean squared error = 120.58, p = .006; R2 = 0.09, p = .025). In post hoc analyses, hippocampal rsFC remained significant after controlling
for demographics, PTSD symptoms at baseline, and depression, anxiety, and stress severity
at 6 months (B = 0.59, SE = 0.20, p = .003).
Conclusions
Findings suggest that functional connectivity of the hippocampus across the brain
acutely after traumatic injury is associated with prospective PTSD symptom severity.
Keywords
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Article Info
Publication History
Published online: August 31, 2021
Accepted:
August 22,
2021
Received in revised form:
July 18,
2021
Received:
March 14,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
