Predictors of Neurocognitive Syndromes in Combat Veterans

Abstract

Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes.

Keywords: biomarkers; combat military veterans; depression; neuroimaging; posttraumatic stress disorder; traumatic brain injury.

Figure 1. Multivariate analysis using decision tree (CART). Visual representation of final result of the decision trees.

Figure 2. Resting state functional connectivity at baseline (2 months after deployment to Iraq or Afghanistan).

Plot of controls vs. cases from the homogeneous node defined by an SNP in the gene coding for MBP (rs1629089) and resting state connectivity functional connectivity between the right (R) amygdala and left (L) superior temporal gyrus (STG). Left panel is the Pearson’s correlation (Fisher’s z ) between these regions that was significantly associated with development of PTSD (PTSD) and those who did not develop PTSD (control) during 12 month longitudinal follow-up. The right panel illustrates the anatomical locations of the left STG (axial, z-axis MNI coordinate) and right amygdala (coronal, x-axis MNI coordinate).