Traumatic Brain Injury and Posttraumatic Stress Disorder Are Associated with Physical Health Burden among Post-9/11 Women Veterans.

Background: Little research focuses on physical health outcomes of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) among post-9/11 women veterans (WVs). This study examined lifetime TBI, current PTSD, and their associations with biomarkers of cardiometabolic health, sleep, pain, and functional disability among post-9/11 WVs. Methods: WVs (n = 90) from the Translational Research Center for TBI and Stress Disorders longitudinal cohort study were included in this study. Gold standard clinician administered interviews assessed lifetime TBI (Boston Assessment of TBI-Lifetime) and current PTSD symptoms (Clinician-Administered PTSD Scale-IV). Objective measures of health included waist-hip ratio (WHR) and fasted blood biomarker (high density lipoprotein [HDL], low density lipoprotein [LDL], blood glucose, triglycerides) levels. Self-reported surveys assessed sleep, pain, and functional disability. Results: Just under two-thirds (58.9%) of WVs experienced a lifetime TBI, and just over half (53.3%) of this sample had a current PTSD diagnosis at the time of testing. Lifetime TBI was significantly associated with higher WHR, triglycerides levels, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.01 to 1.12). Current PTSD was significantly associated with higher WHR, lower HDL, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.009 to 1.19). PTSD was significantly associated with lower total functioning and each of its subdomains (ßs = -0.58 to 0.63; ps = <0.001 to 0.02). Lifetime TBI was significantly associated with total functioning, mobility, and life/work (ßs = -0.20 to 0.30; ps = <0.01 to 0.02). Conclusions: These findings highlight the importance of screening for lifetime TBI and cardiovascular disease for WVs and support transdiagnostic treatment approaches targeting physical health outcomes.

Intimate partner violence perpetration among veterans: associations with neuropsychiatric symptoms and limbic microstructure.

Background: Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration. Methods: Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA. Results: Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex (r = 0.400, p = 0.005). Conclusion: Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.

Posttraumatic survivor guilt is associated with white matter microstructure alterations.

BACKGROUND: Military veterans with posttraumatic stress disorder (PTSD) commonly experience posttraumatic guilt. Guilt over commission or omission evolves when responsibility is assumed for an unfortunate outcome (e.g., the death of a fellow combatant). Survivor guilt is a state of intense emotional distress experienced by the weight of knowing that one survived while others did not. METHODS: This study of the Translational Research Center for TBI and Stress Disorders (TRACTS) analyzed structural and diffusion-weighted magnetic resonance imaging data from 132 male Iraq/Afghanistan veterans with PTSD. The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) was employed to classify guilt. Thirty (22.7 %) veterans experienced guilt over acts of commission or omission, 34 (25.8 %) experienced survivor guilt, and 68 (51.5 %) had no posttraumatic guilt. White matter microstructure (fractional anisotropy, FA), cortical thickness, and cortical volume were compared between veterans with guilt over acts of commission or omission, veterans with survivor guilt, and veterans without guilt. RESULTS: Veterans with survivor guilt had significantly lower white matter FA compared to veterans who did not experience guilt (p < .001), affecting several regions of major white matter fiber bundles. There were no significant differences in white matter FA, cortical thickness, or volumes between veterans with guilt over acts of commission or omission and veterans without guilt (p > .050). LIMITATIONS: This cross-sectional study with exclusively male veterans precludes inferences of causality between the studied variables and generalizability to the larger veteran population that includes women. CONCLUSION: Survivor guilt may be a particularly impactful form of posttraumatic guilt that requires specific treatment efforts targeting brain health.

STEP-Home transdiagnostic group reintegration workshop to improve mental health outcomes for post-9/11 Veterans: Design, methods, and rationale for a randomized controlled behavioral trial.

BACKGROUND: Many post-9/11 U.S. combat Veterans experience difficulty readjusting to civilian life after military service, including relationship problems, reduced work productivity, substance misuse, and increased anger control problems. Mental health problems are frequently cited as causing these difficulties, driven by unparalleled rates of mild traumatic brain injury, posttraumatic stress, and other co-occurring emotional and physical conditions. Given the high prevalence of multimorbidity in this cohort, acceptable, non-stigmatizing, transdiagnostic interventions targeting reintegration are needed. The STEP-Home reintegration workshop has the potential to significantly improve skills to foster civilian reintegration, increase engagement in VA services, and improve mental health outcomes in Veterans with and without diagnosed clinical conditions. METHODS/DESIGN: Ongoing from 2019, a prospective, two-site, randomized trial of 206 post-9/11 U.S. military Veterans randomized to receive either 12 sessions of the STEP-Home transdiagnostic reintegration workshop (SH; Active Intervention) or Present Centered Reintegration Group Therapy (PCRGT; Active Control Intervention). Primary outcomes are reintegration, anger, and emotional regulation post-intervention and at 3-months post-intervention. Secondary outcomes include measures of mental health, functional and vocational status, and cognition. CONCLUSION: This study addresses an important gap in transdiagnostic interventions to improve civilian reintegration in post-9/11 Veterans. STEP-Home is designed to promote treatment engagement and retention, opening the door to critically needed VA care, and ultimately reducing long-term healthcare burden of untreated mental health illness in U.S. Veterans. TRIAL REGISTRATION: Clinicaltrials.gov: D2907-R.

Association of mild traumatic brain injury, post-traumatic stress disorder, and other comorbidities on photosensitivity.

SIGNIFICANCE: Photosensitivity is common after mild traumatic brain injury. However, this study demonstrates that photosensitivity is also impacted by common comorbidities that often occur with mild traumatic brain injury. Understanding how physical and psychological traumas impact photosensitivity can help improve provider care to trauma survivors and guide novel therapeutic interventions. PURPOSE: This study aimed to characterize the association between mild traumatic brain injury and common comorbidities on photosensitivity in post-9/11 veterans. METHODS: Existing data from the Translational Research Center for TBI and Stress Disorders cohort study were analyzed including traumatic brain injury history and post-traumatic stress disorder clinical diagnostic interviews; sleep quality, anxiety, and depression symptoms self-report questionnaires; and photosensitivity severity self-report from the Neurobehavioral Symptom Inventory. Analysis of covariance and multiple ordinal regression models were used to assess associations between mild traumatic brain injury and common comorbidities with photosensitivity severity. RESULTS: Six hundred forty-one post-9/11 veterans were included in this study. An initial analysis showed that both mild traumatic brain injury and current post-traumatic stress disorder diagnosis were independently associated with higher photosensitivity ratings compared with veterans without either condition, with no interaction observed between these two conditions. Results of the ordinal regression models demonstrated positive associations between degree of photosensitivity and the number of mild traumatic brain injuries during military service and current post-traumatic stress disorder symptom severity, particularly hyperarousal symptoms, even when controlling for other factors. In addition, the degree of sleep disturbances and current anxiety symptoms were both positively associated with photosensitivity ratings, whereas depression symptoms, age, and sex were not. CONCLUSIONS: Repetitive mild traumatic brain injury, post-traumatic stress disorder, anxiety, and sleep disturbances were all found to significantly impact photosensitivity severity and are therefore important clinical factors that eye care providers should consider when managing veterans with a history of deployment-related trauma reporting photosensitivity symptoms.

Importance of validity testing in psychiatric assessment: evidence from a sample of multimorbid post-9/11 veterans.

OBJECTIVE: Performance validity (PVTs) and symptom validity tests (SVTs) are necessary components of neuropsychological testing to identify suboptimal performances and response bias that may impact diagnosis and treatment. The current study examined the clinical and functional characteristics of veterans who failed PVTs and the relationship between PVT and SVT failures. METHOD: Five hundred and sixteen post-9/11 veterans participated in clinical interviews, neuropsychological testing, and several validity measures. RESULTS: Veterans who failed 2+ PVTs performed significantly worse than veterans who failed one PVT in verbal memory (Cohen's d = .60-.69), processing speed (Cohen's d = .68), working memory (Cohen's d = .98), and visual memory (Cohen's d = .88-1.10). Individuals with 2+ PVT failures had greater posttraumatic stress (PTS; ß = 0.16; p = .0002), and worse self-reported depression (ß = 0.17; p = .0001), anxiety (ß = 0.15; p = .0007), sleep (ß = 0.10; p = .0233), and functional outcomes (ß = 0.15; p = .0009) compared to veterans who passed PVTs. 7.8% veterans failed the SVT (Validity-10; ≥19 cutoff); Multiple PVT failures were significantly associated with Validity-10 failure at the ≥19 and ≥23 cutoffs (p's < .0012). The Validity-10 had moderate correspondence in predicting 2+ PVTs failures (AUC = 0.83; 95% CI = 0.76, 0.91). CONCLUSION: PVT failures are associated with psychiatric factors, but not traumatic brain injury (TBI). PVT failures predict SVT failure and vice versa. Standard care should include SVTs and PVTs in all clinical assessments, not just neuropsychological assessments, particularly in clinically complex populations.

Associations Between Head Injury, Strangulation, Cardiometabolic Health, and Functional Disability Among Female Survivors of Intimate Partner Violence.

OBJECTIVE: Head injury and strangulation are highly prevalent in intimate partner violence (IPV) contexts, but there is little research examining the potential implications of these injuries on physical health and functional status. This pilot study explored the extent to which injury type (head injury, strangulation) and severity (no injury, subconcussive head injury, traumatic brain injury; no strangulation, strangulation, strangulation with loss of consciousness) were associated with biomarkers of cardiometabolic health and self-reported functioning among female survivors of IPV. METHODS: Participants were 51 individuals assigned female at birth who experienced IPV during their lifetime and screened positive for probable posttraumatic stress disorder (PTSD) on the PTSD Checklist for DSM-5 (average age = 32.6 years, SD = 7.1). RESULTS: Head injury was associated with statistically significant increases in blood glucose levels (p = .01, d = 1.10). Shifts toward more high-risk values with moderate-strong effect sizes were also found in high-density lipoprotein, low-density lipoprotein, and waist-to-hip ratio (ps: .06-.13; ds: 0.51-1.30). Strangulation was associated with increased cholesterol levels, with a moderate effect size (p = .20, d = 0.59). Regression models accounting for age, education, PTSD symptoms, childhood trauma, strangulation, and head injuries predicted functional disability status (R2 = 0.37, p < .01) and several of its associated domains: cognition (R2 = 0.34, F(8,42) = 2.73, p = .01), mobility (R2 = 0.47, F(8,42) = 4.82, p < .001), and participation in society (R2 = 0.33, F(8,42) = 2.59, p = .02). CONCLUSIONS: Findings suggest the need to develop integrated treatments that address physical health comorbidities among female survivors of IPV with a history of head injury to improve daily function and quality of life.

Early onset adolescent binge drinking is associated with reduced white matter integrity in post-9/11 adult veterans.

Adolescence represents a critical period of neural development during which binge drinking (BD) is prevalent. Though prior work has shown that white matter (WM) integrity is susceptible to damage from excessive alcohol intake in adults, the effect of early adolescent BD on WM health in adulthood remains unknown. Veterans with a history of BD onset before age 15 [n = 49; mean age = 31.8 years; early-onset adolescent binge drinkers (EBD)] and after age 15 [n = 290; mean age = 32.2 years; late-onset adolescent binge drinkers (LBD)] were studied with diffusion tensor imaging. Group differences in fractional anisotropy (FA; movement of water molecules along the WM) and mean diffusivity (MD; average movement of water molecules) were examined as indices of WM integrity using FreeSurfer and FMRIB Software Library (FSL) processing streams. Lower FA and higher MD are thought to represent degradations in WM integrity. A reference group (RG) of social drinkers with no history of BD (n = 31) was used to provide comparative normative data. We observed widespread decreased FA and increased MD in EBDs, compared to LBDs, as well as decreased FA in the pars triangularis, lateral orbitofrontal cortex, superior frontal cortex, isthmus cingulate, and genu and splenium of the corpus callosum EBDs also had lower WM integrity compared to the RG. Adults who initiated BD during early adolescence demonstrated decreased FA and increased MD throughout the frontostriatal circuits that mediate inhibitory control and thus may result in impulsive behavior and a predisposition for developing alcohol use disorder during adulthood.

Inhibitory control and alcohol use history predict changes in posttraumatic stress disorder symptoms.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with significant disability and can become chronic. Predictors of PTSD symptom changes over time, especially in those with a PTSD diagnosis, remain incompletely characterized. METHOD: In the present study, we examined 187 post-9/11 veterans (Mage = 32.8 years, 87% male) diagnosed with PTSD who performed two extensive clinical and cognitive evaluations approximately 2 years apart. RESULTS: We found that greater PTSD symptom reductions over time were related to lower lifetime drinking history and better baseline inhibitory control ability (Color-Word Inhibition and Inhibition/Switching), though not performance on other executive function tasks. Further, groups with reliably Improved, Worsened, or Chronic PTSD symptoms demonstrated significant differences in baseline inhibitory control and lifetime drinking history, with marked drinking differences starting in the early-to-mid 20s. We also found that PTSD symptom changes showed little-to-no associations with changes in inhibitory control or alcohol consumption. CONCLUSIONS: Together, these findings suggest that, in those diagnosed with PTSD, inhibitory control and alcohol use history reflect relatively stable risk/resiliency factors predictive of PTSD chronicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.

Approximately 10%-30% of individuals with posttraumatic stress disorder (PTSD) exhibit a dissociative subtype of the condition defined by symptoms of depersonalization and derealization. This study examined the psychometric evidence for the dissociative subtype of PTSD in a sample of young, primarily male post-9/11-era Veterans (n = 374 at baseline and n = 163 at follow-up) and evaluated its biological correlates with respect to resting state functional connectivity (default mode network [DMN]; n = 275), brain morphology (hippocampal subfield volume and cortical thickness; n = 280), neurocognitive functioning (n = 337), and genetic variation (n = 193). Multivariate analyses of PTSD and dissociation items suggested a class structure was superior to dimensional and hybrid ones, with 7.5% of the sample comprising the dissociative class; this group showed stability over 1.5 years. Covarying for age, sex, and PTSD severity, linear regression models revealed that derealization/depersonalization severity was associated with: decreased DMN connectivity between bilateral posterior cingulate cortex and right isthmus (p = .015; adjusted-p [padj] = .097); increased bilateral whole hippocampal, hippocampal head, and molecular layer head volume (p = .010-.034; padj = .032-.053); worse self-monitoring (p = .018; padj = .079); and a candidate genetic variant (rs263232) in the adenylyl cyclase 8 gene (p = .026), previously associated with dissociation. Results converged on biological structures and systems implicated in sensory integration, the neural representation of spatial awareness, and stress-related spatial learning and memory, suggesting possible mechanisms underlying the dissociative subtype of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Impact of Blast Exposure-With or Without Traumatic Brain Injury-on Metabolic Abnormalities in Post-9/11 Veterans.

OBJECTIVE: The primary aim included explorations of: (1) the associations between the history of blast exposure (BE), close blast exposure (CBE), and blast-related traumatic brain injury (bTBI) and metabolic abnormality; and (2) the potential mediating effect of comorbid psychological and somatic conditions on these associations. The secondary aim explored the association of dose-response impact of BE, CBE, and bTBI and metabolic abnormality. SETTING: Data were collected by the Translational Research Center for TBI and Stress Disorders (TRACTS). PARTICIPANTS: Post-9/11 veterans from the TRACTS baseline sample who had conflict-zone deployment experience ( N = 734). DESIGN: Cross-sectional secondary data analysis. We computed relative risks (RRs) and 95% CI using modified Poisson regression. We quantified the impact of co-occurring psychological and somatic conditions on this association using mediation analyses. MAIN MEASURES: Exposures included BE (<100 m), CBE (<10 m), and bTBI. Metabolic abnormality outcomes included (1) overweight/obesity (defined by abnormal waist-hip ratio [WHR] and abnormal waist circumference [WC]); (2) glucose dysregulation; and (3) meeting criteria for cardiometabolic syndrome (defined by guidelines). RESULTS: The sample was majority male (91%) and White (68%), with a mean age of 34.6 years (SD = 8.99). Most participants had 1 or more BE (83%); 48% experienced 1 or more CBE. Overweight/obesity was highly prevalent in the sample (51% had abnormal WHR and 60% abnormal WC). There was no significant direct or indirect association between BE, CBE, and bTBI and metabolic abnormalities (RRs: 0.70-1.51; P 's > .05). CONCLUSION: Future research is needed to investigate the association of BE with metabolic abnormalities with larger, more targeted sample selection, and longer follow-up. Effective and sustainable weight management and metabolic health prevention interventions for this veteran cohort are needed.

Sleep Quality Disturbances Are Associated with White Matter Alterations in Veterans with Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury.

Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (n = 38), (2) mTBI (n = 25), (3) comorbid PTSD+mTBI (n = 94), and (4) a control group with neither PTSD nor mTBI (n = 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (p = 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (p < 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (p < 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions.

Intimate partner violence and brain imaging in women: A neuroimaging literature review.

PRIMARY OBJECTIVE: Despite a high prevalence of intimate partner violence (IPV) and its lasting impacts on individuals, particularly women, very little is known about how IPV may impact the brain. IPV is known to frequently result in traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). In this overview of literature, we examined literature related to neuroimaging in women with IPV experiences between the years 2010-2021. RESEARCH DESIGN: Literature overview. METHODS AND PROCEDURES: A total of 17 studies were included in the review, which is organized into each imaging modality, including magnetic resonance imaging (structural, diffusion, and functional MRI), Electroencephalography (EEG), proton magnetic resonance spectroscopy (pMRS), and multimodal imaging. MAIN OUTCOMES AND RESULTS: Research has identified changes in brain regions associated with cognition, emotion, and memory. Howeverto date, it is difficult to disentangle the unique contributions of TBI and PTSD effects of IPV on the brain. Furthermore, experimental design elements differ considerably among studies. CONCLUSIONS: The aim is to provide an overview of existing literature to determine commonalities across studies and to identify remaining knowledge gaps and recommendations for implementing future imaging studies with individuals who experience IPV.

Poorer Inhibitory Control Uniquely Contributes to Greater Functional Disability in Post-9/11 Veterans.

OBJECTIVE: Post-9/11 Veterans endorse greater self-reported functional disability than 80% of the adult population. Previous studies of trauma-exposed populations have shown that increased post-traumatic stress disorder (PTSD) and depressive symptoms are consistently associated with greater disability. Additionally, poorer cognitive performance in the domain of executive functions, particularly inhibitory control, has been associated with disability, though it is unclear if this effect is independent of and/or interacts with PTSD and depression. METHOD: Three overlapping samples of n = 582, 297, and 183 combat-deployed post-9/11 Veterans completed comprehensive assessments of executive functions, PTSD and depressive symptoms, and self-reported World Health Organization Disability Assessment Schedule-II (WHODAS II). RESULTS: Poorer performance on measures of inhibitory control (Delis-Kaplan Executive Functioning System Color-Word Interference-CWI Test and gradual-onset Continuous Performance Test-gradCPT), but not other executive functions, were significantly associated with greater disability on the WHODAS II (ρ's = -.13 and -.13, p = .002 and .026, respectively). CWI inhibitory control measures accounted for unique variance in disability after controlling for PTSD and depressive symptoms (R2 change = 0.02, p < .001). Further, CWI significantly moderated the effect of depressive symptoms on disability, such that better inhibitory control weakened the relationship between depression and disability. CONCLUSIONS: Inhibitory control deficits are uniquely associated with increased disability in combat-deployed post-9/11 Veterans, and better inhibitory control abilities may serve as a protective factor for depressive symptoms leading to increased disability.

Diagnostic Accuracy of the Boston Assessment of Traumatic Brain Injury-Lifetime Clinical Interview Compared to Department of Defense Medical Records.

INTRODUCTION: Since 2006, efforts have been made to increase the accurate identification of traumatic brain injuries (TBIs) in post-9/11 military personnel. The Boston Assessment of TBI-Lifetime (BAT-L) is the first validated instrument designed specifically to diagnose TBIs throughout the life span in post-9/11 Veterans. The objective was to compare the diagnostic accuracy of the BAT-L with medical records from the Department of Defense (DoD). MATERIAL AND METHODS: Traumatic brain injury diagnosis for 153 Veterans deployed in 2011 enrolled in the Translational Research Center for TBI and Stress Disorder longitudinal cohort study from the BAT-L clinical interview was compared to DoD online medical records to determine diagnostic prevalence and injury severity for all head injury cases during deployment. Sensitivity, specificity, Cohen's kappa, and Kendall's tau-b were calculated for TBI diagnosis and severity. Concordant TBI cases and discordant TBI cases were compared using chi-square and t-test analyses. This study has been approved by VA Boston by Institutional Review Boards for human participants' protection. RESULTS: Correspondence of TBI diagnoses from the BAT-L with DoD records was fair (κ = 0.42; sensitivity = 72.7%; specificity = 82.8%). Comparison of injury severity also showed fair correspondence (κ = 0.41). Missing TBI diagnostic data from DoD records were frequent; 43% of TBIs reported on the BAT-L did not have any documentation of assessment or diagnoses in DoD records. CONCLUSION: This study addresses a critical gap in research by comparing the diagnostic accuracy of a validated, semi-structured clinical interview with available medical records. Diagnosis of TBIs via the BAT-L was both sensitive and specific when compared to DoD records, supporting the validity of the BAT-L for retrospective assessment of military TBI. However, diagnostic correspondence was only fair. This lack of diagnostic agreement was related to multiple factors including lack of documentation at the time of injury by DoD, differences in assessment and goals, and other combat-related motivational factors associated with failure to report injuries while deployed. Several policies have been implemented to address underreporting and under-documentation of TBIs, yet challenges remain. Recommendations for evaluating TBI are presented. Accurate diagnosis of TBI is necessary for appropriate treatment planning, as well as service-related compensation.

Depressive symptoms exacerbate disability in older adults: A prospective cohort analysis of participants in the MemAID trial.

BACKGROUND: Maintaining independence in older age is an important aspect of quality of life. We investigated depressive symptoms as an important modifiable risk factor that may mediate the effects of physical and cognitive decline on disability. METHODS: We prospectively analyzed data from 223 adults (age 50-85; 117 controls and 106 with type-2 diabetes) over 48 weeks who were participating in a clinical trial "Memory Advancement by Intranasal Insulin in Type 2 Diabetes." Data from self-reported disability (World Health Organization Disability Assessment Schedule) and depressive symptoms (Geriatric Depression Scale) were obtained from baseline, week 25, and week 48 visits. Cognition (Mini-mental status examination) and medical comorbidities (Charlson Comorbidity Index) were assessed at baseline. Longitudinal analysis assessed the extent to which change in depressive symptoms predicted worsening disability. Mediation analyses were performed to determine the extent to which depressive symptoms accounted for disability associated with worse cognition, walking speed, and comorbidities. RESULTS: At baseline, depressive symptoms, cognition, and walking speed were within normal limits, but participants had a high 10-year risk of cardiovascular mortality. Depressive symptoms were related to disability at baseline (p<0.001), and longitudinally (p<0.001). Cognition, walking speed, and comorbidities were associated with disability at baseline (p-values = 0.027-0.001). Depressive symptoms had a large mediating effect on disability longitudinally: the indirect effect on disability via depression accounts for 51% of the effect of cognition, 34% of the effect of mobility, and 24% of the effect of comorbidities. CONCLUSIONS: Depressive symptoms substantially exacerbated the effects of worsening cognition, gait speed, and comorbidities on disability. In our sample, most individuals scored within the "normal" range of the Geriatric Depression Scale, suggesting that even subclinical symptoms can lead to disability. Treating subclinical depression, which may be under-recognized in older adults, should be a public health priority to help preserve independence with aging.

Association of War Zone-Related Stress With Alterations in Limbic Gray Matter Microstructure.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Exposures: 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. Main Outcomes and Measures: Diffusion characteristics (fractional anisotropy of tissue [FAT]) of 16 limbic and paralimbic GM regions and measures of functional outcome. Results: 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 association between war zone-related stress and GM diffusion. Conclusions and Relevance: 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.

PTSD symptomatology is selectively associated with impaired sustained attention ability and dorsal attention network synchronization.

Posttraumatic Stress Disorder (PTSD) symptomatology is associated with dysregulated sustained attention, which produces functional impairments. Performance on sustained attention paradigms such as continuous performance tasks are influenced by both the ability to sustain attention and response strategy. However, previous studies have not dissociated PTSD-related associations with sustained attention ability and strategy, which limits characterization of neural circuitry underlying PTSD-related attentional impairments. Therefore, we characterized and replicated PTSD-related associations with sustained attention ability and response strategy in trauma-exposed Veterans, which guided characterization of PTSD-related differences in neural circuit function. In Study 1, PTSD symptoms were selectively associated with reduced sustained attention ability, but not more impulsive response strategies. In Study 2, we utilized task and resting-state fMRI to characterize neural circuitry underlying PTSD-related differences in sustained attention ability. Both PTSD symptomatology and sustained attention ability exhibited converging associations with reduced dorsal attention network (DAN) synchronization to endogeneous attentional fluctuations. Post-hoc time course analyses demonstrated that PTSD symptoms were most accurately characterized by delayed, rather than globally reduced, DAN synchronization to endogenous attentional fluctuations. Together, these findings suggest that PTSD symptomatology may selectively impair sustained attention ability by disrupting proactive engagement of attentional control circuitry.

Network analysis of mild traumatic brain injury, persistent neurobehavioral and psychiatric symptoms, and functional disability among recent-era United States veterans.

Recent-era U.S. veterans are clinically complex, with a high prevalence of co-occurring mild traumatic brain injury (mTBI), psychiatric conditions, and behavioral dysfunction. The current study examined the direct and indirect associations between mTBI and persistent neurobehavioral, psychiatric, and functional disability symptoms among recent-era U.S. veterans and service members (n = 648). We evaluated the postconcussive syndrome (PCS) potential causal model with two network analysis modeling approaches. Separate analyses were conducted for military mTBI and lifetime mTBI. An exploratory factor analysis was conducted to limit topological overlap in the network analysis. The most influential symptoms (i.e., the unique variables most strongly associated with the rest of the network) in the military mTBI network were behavioral disengagement, expected influence (EI) = 1.10; cognitive difficulties, EI = 1.08; agitation/irritability, EI = 1.05; and PTSD-related reexperiencing and avoidance symptoms, EI = 0.98. After accounting for other symptoms, mTBI was only minimally informative, EI = 0.34. Additionally, military mTBI did not moderate the association between symptoms or the overall connectivity of the network. The results for lifetime mTBI were consistent with those for military mTBI. The present analyses identified a variety of behavioral, cognitive, and emotional symptoms that play an important role in understanding comorbidity and daily functioning among recent-era U.S. veterans. Associations between cumulative mTBI that occurred in civilian or military settings were indirect and relatively small in magnitude. The current results add to a growing literature raising doubts about the PCS model.

Contributory Etiologies to Cognitive Performance in Multimorbid Post-9/11 Veterans: The Deployment Trauma Phenotype.

OBJECTIVE: This study examined cognitive functioning in post-9/11 Veterans with the deployment trauma phenotype (DTP), comprised of co-occurring diagnoses of depressive disorder (major depressive disorder and or persistent depressive disorder/dysthymia), posttraumatic stress disorder (PTSD), and mild traumatic brain injury (mTBI), using objective neuropsychological measures. METHOD: Participants included a cross-sectional sample of 399 post-9/11 Veterans who completed clinical interviews and neuropsychological tests as part of a larger study at VA Boston Healthcare System. Confirmatory factor analysis identified four cognitive domains: attention, cognitive control/processing speed, episodic memory, and cognitive flexibility. Veterans with DTP and its constituent diagnoses in isolation, two-way diagnostic combinations, and no constituent diagnoses were compared. RESULTS: Veterans with DTP had a twofold increased prevalence for below average performance in cognitive control/processing speed compared with those with no constituent diagnoses (prevalence ratios [PRs] = 2.04; 95% confidence interval [CI]: 1.03-4.05). The PTSD + depressive disorder group also had a twofold increased prevalence for below average performance in episodic memory (PR = 2.16; 95% CI: 1.05-4.43). CONCLUSIONS: The deployment trauma phenotype is associated with clinically significant decrease in cognitive control/processing speed in post-9/11 Veterans. Comorbid PTSD and depressive disorder negatively impacted performances in episodic memory. Mild TBI alone showed no cognitive deficits. Clinical interventions should target psychiatric symptoms with a transdiagnostic approach to address this multimorbid population.