Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort.

Mild traumatic brain injury (mTBI) is among the most common injuries sustained by post-9/11 veterans; however, these injuries often occur within the context of psychological trauma. Blast exposure, even in the absence of a diagnosable TBI, leads to changes in neural connectivity and congitive functioning. Therefore, considering clinical comorbidities and injury characteristics is critical to understanding the long-term effects of mTBI. Research is moving towards identifying diagnostic and prognostic blood-based biomarkers for TBI; however, few studies include other prevalent clinical and medical comorbidities related to deployment. Here, we present the initial cross-sectional relationships between plasma biomarkers, clinical, and medical comorbidities in a well-characterized longitudinal sample of 550 post-9/11 veteran men and women. We examined biomarkers associated with inflammation (interleukin 6 and 10, tumor necrosis factor α, and eotaxin) and neurodegeneration (neurofilament light, glial fibrillary acidic protein (GFAP), tau, brain derived neurotrophic factor, amyloid ß 40 and 42, phosphorylated neurofilament heavy chain, and neuron specific enolase). Univariate analyses of covariance (ANCOVA) were conducted to determine mean level differences between close blast (blasts that occur within 0-10 meters) and mTBI groups. Our primary findings were twofold: (1) Inflammatory markers were consistently higher in participants exposed to close blasts and were strongly related to deployment-related psychopathology. (2) GFAP was consistently lower in participants exposed to blast and mTBI and lower GFAP was associated with more severe psychological symptoms. More research is clearly needed; however, our findings indicate that chronic increased inflammation and decreased GFAP may be related to close blast exposure.

Cardiorespiratory Fitness Is Associated With Better Cardiometabolic Health and Lower PTSD Severity in Post-9/11 Veterans.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular and metabolic diseases and physical inactivity. Cardiorespiratory fitness (CRF), which is modifiable by physical activity, is a strong independent predictor of cardiometabolic health. However, the relationship between CRF and cardiometabolic health in veterans with PTSD is unknown. Thus, this study aimed to explore the cross-sectional relationships among CRF, indices of cardiometabolic health (ie, HbA1c, blood lipids, blood pressure, waist-hip ratio, and body mass index), and PTSD severity in veterans with PTSD. MATERIALS AND METHODS: This study was approved by the local Institutional Review Board. All participants were informed of the study risks and provided consent prior to participation. Participants (n = 13) completed a cardiopulmonary exercise test, a fasting blood draw, and the Clinician Administered PTSD Scale. Correlations between CRF and cardiometabolic health were examined with Spearman's rank correlations, and differences in PTSD symptom severity were explored as a function of CRF (ie, low-to-moderate vs. high CRF), using multiple linear regression. RESULTS: Peak oxygen uptake ($\dot{\mathrm{V}}$O2peak) was correlated with high-density lipoproteins rho = 0.60, P = 0.04 and diastolic blood pressure rho = -0.56, P = 0.05. Ventilatory threshold was correlated with HbA1c rho = -0.61, P = 0.03 and diastolic blood pressure rho = -0.56, P = 0.05. Higher CRF was associated with lower total PTSD severity standardized ß = -0.84, P = 0.01, adjusted R2 = 0.47, total Cluster C symptoms (avoidance/numbing) ß = -0.71, P = 0.02, adjusted R2 = 0.49, and total Cluster D symptoms (hyperarousal) ß = -0.89, P = 0.01, adjusted R2 = 0.41, while adjusting for age and smoking status. CONCLUSIONS: These preliminary findings suggest that CRF and by proxy physical activity may be important factors in understanding the increased risk of cardiovascular and metabolic disease associated with PTSD.

Tobacco dependence is associated with increased risk for multi-morbid clustering of posttraumatic stress disorder, depressive disorder, and pain among post-9/11 deployed veterans.

RATIONALE: Tobacco use is highly prevalent among individuals with posttraumatic stress disorder (PTSD), depressive disorders, and pain. Research has revealed pairwise relationships among these conditions but has not examined more complex relationships that may influence symptom severity, chronicity, and treatment outcome. OBJECTIVE: To examine the clustering of current PTSD, depressive disorders, and clinically significant pain according to current tobacco use and dependence among post-9/11 deployed veterans. METHODS: Logistic regression was used to examine the clustering of these conditions in relationship to current tobacco use/dependence, while adjusting for age and total combat exposure, in 343 post-9/11 deployed veterans enrolled in the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort (Mage = 32.1 + 8.3 years; 38% current tobacco use; 25% low and 12% moderate/high tobacco dependence). RESULTS: A three-way clustering of PTSD, depressive disorder, and pain was more likely than any single or pairwise combination of these conditions in moderate/high tobacco-dependent veterans compared to tobacco non-users (adjusted ORs = 3.50 to 4.18). This multi-morbidity cluster also was associated with increased PTSD severity. CONCLUSIONS: Moderate to high dependence on tobacco is associated with substantially increased clustering of PTSD, depression, and clinically significant pain in veterans. Research examining synergistic interactions among these conditions, biological vulnerabilities shared among them, and the direct impact of tobacco use on the pathophysiology of PTSD, depression, and pain is needed. The results of such work may spur development of more effective integrated treatments to reduce the negative impact of these multi-morbid conditions on veterans' wellbeing and long-term health.