Depressive Symptoms and Supraspinal Functional Connectivity in Veterans with Gulf War Illness-related Chronic Pain

Both chronic pain and depressive symptoms are highly prevalent in Veterans with Gulf War illness(GWI). This study assessed how the severity of depressive symptoms may correlate with pain symptomology and supraspinal pain modulatory functional connectivity(FC) in the Veterans with GWI-related chronic H eadache, A nd body muscle and joint P ain conditions(GWI-HAP). Resting state fMRI region of interest (ROI)-to-ROI FC analyses indicated the Veterans with GWI-HAP and moderate to severe depressive symptoms reflected by Hamilton Rating Scale for Depression score ≥14(GWI≥14) showed significantly enhanced FC with the adjacent frontal cortex(Brodmann Area[BA] 44; P < 0.001; t = 4.64) and the contralateral Insula(BA 13; P < 0.001; t = 7.14), and two regions of contralateral thalamus(P < 0.01, P < 0.001; t = 5.32, t = 5.25 respectively); and decreased FC with the ipsilateral premotor cortex(BA 6; P < 0.01; t = -3.34) and contralateral anterior cingulate cortex(BA 32; P < 0.001; t = -3.64) than their counterparts with no or mild depressive symptoms(GWI < 14). These findings are correlated with more pain symptomology, and functional and quality of life impairments found in the GWI≥14 group. Potential therapeutic interventions applicable for addressing both highly prevalent co-morbid conditions may utilize this mechanistic correlation.