Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach
Biological Psychiatry : Cognitive Neuroscience and Neuroimaging
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. Prior small-scale research (n < 25) has also shown that hippocampal-rsFC measured acutely after trauma is predictive of future severity using an ROI-based approach. While a promising biomarker, to-date no study has employed a data-driven approach to test whole-brain hippocampal-FC patterns in forecasting the development of PTSD symptoms.
Methods: Ninety-eight adults at risk of PTSD were recruited from the emergency department following traumatic injury and completed resting functional magnetic resonance imaging (rsfMRI; 8min) within 1-month; 6-months later they completed the Clinician-Administered PTSD Scale (CAPS-5) for assessment of PTSD symptom severity. Whole-brain rsFC values with bilateral hippocampi were extracted (CONN) and used in a machine learning kernel ridge regression analysis (PRoNTo); both a k-folds (k=10) and 70/30 testing vs. training split approach were used for cross-validation (1,000 iterations to bootstrap confidence intervals for significance values).
Results: Acute hippocampal-rsFC significantly predicted CAPS-5 scores at 6-months (r=0.30, p=0.006; MSE=120.58, p=0.006; R2=0.09, p=0.025). 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=0.003).
Conclusions: Findings suggest functional connectivity of the hippocampus across the brain acutely after traumatic injury is associated with prospective PTSD symptom severity
Fitzgerald, Jacklynn M.; Webb, Elisabeth Kate; Weis, Carissa N.; Huggins, Ashley A.; Bennett, Kenneth P.; Miskovich, Tara A.; Krukowski, Jessica L.; deRoon-Cassini, Terri A; and Larson, Christine L., "Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach" (2022). Psychology Faculty Research and Publications. 542.
Accepted version. Biological Psychiatry : Cognitive Neuroscience and Neuroimaging, Vol. 7, No. 2 (February 2022): 139-149. DOI. © 2022 Elsevier. Used with permission.