Previous work identified a cognitive subtype of PTSD with impaired executive function (i.e., impaired EF-PTSD subtype) and aberrant resting-state functional connectivity between frontal parietal control (FPCN) and limbic (LN) networks. To better characterize this cognitive subtype of PTSD, this study investigated (1) alterations in specific FPCN and LN subnetworks and (2) chronicity of PTSD symptoms. In a post-9/11 veteran sample (N = 368, 89% male), we identified EF subgroups using a standardized neuropsychological battery and a priori cutoffs for impaired, average, and above-average EF performance. Functional connectivity between two subnetworks of the FPCN and three subnetworks of the LN was assessed using resting-state fMRI (n = 314). PTSD chronicity over a 1–2-year period was assessed using a reliable change index (n = 175). The impaired EF-PTSD subtype had significantly reduced negative functional connectivity between the FPCN subnetwork involved in top-down control of emotion and two LN subnetworks involved in learning/memory and social/emotional processing. This impaired EF-PTSD subtype had relatively chronic PTSD, while those with above-average EF and PTSD displayed greater symptom reduction. Lastly, FPCN-LN subnetworks partially mediated the relationship between EF and PTSD chronicity (n = 121). This study reveals (1) that an impaired EF-PTSD subtype has a specific pattern of FPCN-LN subnetwork connectivity, (2) a novel above-average EF-PTSD subtype displays reduced PTSD chronicity, and (3) both cognitive and neural functioning predict PTSD chronicity. The results indicate a need to investigate how individuals with this impaired EF-PTSD subtype respond to treatment, and how they might benefit from personalized and novel approaches that target these neurocognitive systems.

Maladaptive anger and aggression are common in US military veterans and increase risk for impaired social relationships and functioning, justice-involvement and violence. Early life (before age 18) adversity predisposes veterans to later life psychopathology, though the link to increased later life anger is unclear. We analysed cross-sectional data of 158 post-9/11 veterans from the Translational Research Center for Traumatic Brain Injury and Stress Disorders study with and without a history of early life adversity (ns = 109 and 49, respectively). We explored the relationship among major clinical variables and current veteran anger (Dimensions of Anger Reactions) and whether the associations with these variables differed among participants with and without a history of retrospective self-reported early life adversity (Childhood Trauma Questionnaire). In the overall sample, posttraumatic stress disorder (PTSD) and depression severities had the strongest associations with current veteran anger (βs = 0.261 and 0.263; p-values = 0.0022 and 0.0103, respectively). In the subsample without early life adversity, only PTSD severity was significantly associated with anger (β = 0.577, p = 0.0004). In the early life adversity subsample, this strong association weakened and was no longer significant (β = 0.168, p = 0.1007); instead, anxiety and depression severities showed moderate associations with anger (βs = 0.243 and 0.287, p-values = 0.0274 and 0.0130, respectively). Findings suggest that clinicians should screen veterans with history of early life adversity for depression and anxiety when anger is present.

Veterans who deployed in support of Operation Enduring Freedom (OEF), Iraqi Freedom (OIF), and New Dawn (OND) commonly experience severe psychological trauma, often accompanied by physical brain trauma resulting in mild traumatic brain injury (mTBI). Prior studies of individuals with posttraumatic stress disorder (PTSD) have revealed alterations in brain structure, accelerated cellular aging, and impacts on cognition following exposure to severe psychological trauma and potential interactive effects of military-related mTBI. To date, however, little is known how such deployment-related trauma changes with time and age of injury of the affected veteran. In this study, we explored changes in cortical thickness, volume, and surface area after an average interval of approximately 2 years in a cohort of 254 OEF/OIF/OND Veterans ranging in age from 19 to 67 years. Whole-brain vertex-wise analyses revealed that veterans who met criteria for severe PTSD (Clinician-Administered PTSD Scale ≥60) at baseline showed greater negative longitudinal changes in cortical thickness, volume, and area over time. Analyses also revealed a significant severe-PTSD by age interaction on cortical measures with severe-PTSD individuals exhibiting accelerated cortical degeneration with increasing age. Interaction effects of comorbid military-related mTBI within the severe-PTSD group were also observed in several cortical regions. These results suggest that those exhibiting severe PTSD symptomatology have accelerated atrophy that is exacerbated with increasing age and history of mTBI.

Cross-sectional work suggests that deployment-related posttraumatic sequelae are associated with increased disability in U.S. veterans deployed following the September 11, 2001 (9/11), terrorist attacks. However, few studies have examined the psychiatric and somatic variables associated with changes in functional disability over time. A total of 237 post-9/11 veterans completed comprehensive assessments of psychiatric and cognitive functioning, as well as a disability questionnaire, at baseline and 2-year follow-up. At baseline, higher levels of PTSD, depressive, and pain-related symptoms were associated with baseline global functional disability, semipartial r(2) = .036-.044. Changes in symptoms of PTSD, depression, pain, and sleep, but not anxiety or alcohol use, were independently associated with changes in functional disability, semipartial r(2) = .017-.068. Baseline symptoms of these conditions were unrelated to changes in disability, and cognitive performance was unrelated to disability at any assessment point. Together, this suggests that changes in psychiatric and somatic symptoms are tightly linked with changes in functional disability and should be frequently monitored, and even subclinical symptoms may be a target of intervention.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with inflammation and various forms of chronic disease. The Absent in Melanoma 2 (AIM2) gene has been implicated in mechanisms of inflammation and anxiety, and methylation at a particular locus in this gene (cg10636246) has previously been shown to influence the association between PTSD and elevated C-reactive protein levels in blood. METHOD: We tested if this association might extend to other indicators of inflammation and to plasma-based measures of neuropathology in a cohort of post-9/11 US military veterans. Using a Bayesian approach, mediation models were tested cross-sectionally (n = 478) and longitudinally (n = 298). Peripheral markers of inflammation and neuropathology were measured with ultra-sensitive Single Molecule Array (Simoa®) technology. RESULTS: Analyses revealed indirect effects of PTSD symptom severity on peripheral indices of both inflammation (interleukin [IL]6, IL-10, tumor necrosis factor-α; indirect standardized [std.] ß range = 0.018-0.023, all p-values adjusted for multiple testing [p(adj) ]  0.05) and neuropathology (neurofilament light [NFL]; indirect std. ß = -0.018, p(adj)  = 0.02) via AIM2 methylation. This indirect effect was also evident when predicting IL-10 at a follow-up assessment (indirect std. ß = -0.018, p(adj)  = 0.04) controlling for baseline IL-10. CONCLUSIONS: Given that AIM2 methylation mediated the association between PTSD symptoms and multiple inflammatory and neuropathology markers, our results suggest that AIM2 methylation may offer clinical utility for indexing risk for adverse health outcomes associated with these peripheral indices of inflammation and neuropathology. Results also suggest a possible shared etiology underlying the frequent co-occurrence of inflammation and neuropathology.

Military service members returning from theaters of war are at increased risk for mental illness, but despite high prevalence and substantial individual and societal burden, the underlying pathomechanisms remain largely unknown. Exposure to high levels of emotional stress in theaters of war and mild traumatic brain injury (mTBI) are presumed factors associated with risk for the development of mental disorders.To investigate (1) whether war zone–related stress is associated with microstructural alterations in limbic gray matter (GM) independent of mental disorders common in this population, (2) whether associations between war zone–related stress and limbic GM microstructure are modulated by a history of mTBI, and (3) whether alterations in limbic GM microstructure are associated with neuropsychological functioning.This cohort study was part of the TRACTS (Translational Research Center for TBI and Stress Disorders) study, which took place in 2010 to 2014 at the Veterans Affair Rehabilitation Research and Development TBI National Network Research Center. Participants included male veterans (aged 18-65 years) with available diffusion tensor imaging data enrolled in the TRACTS study. Data analysis was performed between December 2017 to September 2021.The Deployment Risk and Resilience Inventory (DRRI) was used to measure exposure to war zone–related stress. The Boston Assessment of TBI-Lifetime was used to assess history of mTBI. Stroop Inhibition (Stroop-IN) and Inhibition/Switching (Stroop-IS) Total Error Scaled Scores were used to assess executive or attentional control functions.Diffusion characteristics (fractional anisotropy of tissue [FAT]) of 16 limbic and paralimbic GM regions and measures of functional outcome.Among 384 male veterans recruited, 168 (mean [SD] age, 31.4 [7.4] years) were analyzed. Greater war zone–related stress was associated with lower FAT in the cingulate (DRRI-combat left: P = .002, partial r = −0.289; DRRI-combat right: P = .02, partial r = −0.216; DRRI-aftermath left: P = .004, partial r = −0.281; DRRI-aftermath right: P = .02, partial r = −0.219), orbitofrontal (DRRI-combat left medial orbitofrontal cortex: P = .02, partial r = −0.222; DRRI-combat right medial orbitofrontal cortex: P = .005, partial r = −0.256; DRRI-aftermath left medial orbitofrontal cortex: P = .02, partial r = −0.214; DRRI-aftermath right medial orbitofrontal cortex: P = .005, partial r = −0.260; DRRI-aftermath right lateral orbitofrontal cortex: P = .03, partial r = −0.196), and parahippocampal (DRRI-aftermath right: P = .03, partial r = −0.191) gyrus, as well as with higher FAT in the amygdala-hippocampus complex (DRRI-combat: P = .005, partial r = 0.254; DRRI-aftermath: P = .02, partial r = 0.223). Lower FAT in the cingulate-orbitofrontal gyri was associated with impaired response inhibition (Stroop-IS left cingulate: P  .001, partial r = −0.440; Stroop-IS right cingulate: P  .001, partial r = −0.372; Stroop-IS left medial orbitofrontal cortex: P  .001, partial r = −0.304; Stroop-IS right medial orbitofrontal cortex: P  .001, partial r = −0.340; Stroop-IN left cingulate: P  .001, partial r = −0.421; Stroop-IN right cingulate: P  .001, partial r = −0.300; Stroop-IN left medial orbitofrontal cortex: P = .01, partial r = −0.223; Stroop-IN right medial orbitofrontal cortex: P  .001, partial r = −0.343), whereas higher FAT in the mesial temporal regions was associated with improved short-term memory and processing speed (left amygdala-hippocampus complex: P  .001, partial r = −0.574; right amygdala-hippocampus complex: P  .001, partial r = 0.645; short-term memory left amygdala-hippocampus complex: P  .001, partial r = 0.570; short-term memory right amygdala-hippocampus complex: P  .001, partial r = 0.633). A history of mTBI did not modulate the ass ciation between war zone–related stress and GM diffusion.This study revealed an association between war zone–related stress and alteration of limbic GM microstructure, which was associated with cognitive functioning. These results suggest that altered limbic GM microstructure may underlie the deleterious outcomes of war zone–related stress on brain health. Military service members may benefit from early therapeutic interventions after deployment to a war zone.

Veterans who served in post-9/11 conflicts and experience deployment trauma sequelae frequently endorse disability and dissatisfaction with life. Although correlated, disability and life dissatisfaction represent distinct constructs with separate implications for quality of life. We examined associations between deployment trauma sequelae, disability and life dissatisfaction in 288 post-9/11 Veterans. Participants completed assessments of psychiatric, somatic and social functioning. Self-reports evaluating disability and life dissatisfaction were used to group participants based on established criteria (i.e., Disability and Dissatisfaction, Disability Only, Dissatisfaction Only, or No Disability or Dissatisfaction). Multinomial logistic regressions revealed that greater post-traumatic stress disorder (PTSD) and depressive symptom severity were independently associated with increased odds of being in the Disability and Dissatisfaction group, the Disability Only group and the Dissatisfaction Only group, relative to the No Disability or Dissatisfaction group. Number of prior mild traumatic brain injuries (mTBI) was not associated with disability or dissatisfaction after accounting for other trauma sequelae. Social support attenuated the relationship between depression and membership in the Disability and Dissatisfaction group. Participants who reported greater dissatisfaction than disability endorsed greater depression and mTBI frequency. Overall, PTSD and depression convey a heightened risk of both disability and life dissatisfaction, while social support may be protective.

The Clinician-Administered PTSD Scale (CAPS) is used to measure posttraumatic stress symptoms (PTSS) and diagnose posttraumatic stress disorder (PTSD). However, its use, particularly in settings involving longitudinal assessment, has been complicated by changes in the diagnostic criteria between the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (i.e., DSM-IV and DSM-5, respectively). The current sample included trauma-exposed U.S. veterans who were deployed in support of military operations following the September 11, 2001, terrorist attacks (N = 371) and were enrolled in a longitudinal study focused on deployment-related stress and traumatic brain injury. A hybrid clinical interview using item wording from the CAPS for DSM-IV (CAPS-IV) with the addition of items unique to the CAPS for DSM-5 (CAPS-5) was used to assess both DSM-IV and DSM-5 PTSD diagnostic criteria, allowing for the calculation of separate total scores and diagnoses. Diagnostic agreement, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and interrater reliability between CAPS-IV and CAPS-5 were evaluated for the entire sample and stratified by gender. We found high diagnostic agreement (92.9%-95.4%), sensitivity (94.4%-98.2%), specificity (91.7%-92.8%), PPV (89.5%-93.0%), NPV (95.7%-98.1%), and interrater reliability,κ = 0.86-0.91,) for both men and women. The current study supports the use of a hybrid PTSD diagnostic interview assessing both DSM-IV and DSM-5 diagnostic criteria, particularly in situations such as longitudinal studies that may require a feasible method of incorporating changes in diagnostic criteria from the DSM-IV to the DSM-5.