Associations Between Traumatic Brain Injury and Severity of Tinnitus-Related Functional Impairment Among US Military Veterans: A National, Population-Based Study.

OBJECTIVE: To describe associations between a history of traumatic brain injury (TBI) and the severity of tinnitus-related functional impairment among a national, stratified random sample of veterans diagnosed with tinnitus by the Department of Veterans Affairs (VA) healthcare system. SETTING: A multimodal (mailed and internet) survey administered in 2018. Participants: VA healthcare-using veterans diagnosed with tinnitus; veterans with comorbid TBI diagnosis were oversampled. DESIGN: A population-based survey. MAIN MEASURES: TBI history was assessed using International Classification of Diseases (ICD) diagnosis codes in veterans' VA electronic health records. The severity of participants' overall tinnitus-related functional impairment was measured using the Tinnitus Functional Index. Population prevalence and 95% confidence intervals (CIs) were estimated using inverse probability weights accounting for sample stratification and survey nonresponse. Veterans' relative risk ratios of very severe or moderate/severe tinnitus-related functional impairment, versus none/mild impairment, were estimated by TBI history using bivariable and multivariable multinomial logistic regression. RESULTS: The population prevalence of TBI was 5.6% (95% CI: 4.8-6.4) among veterans diagnosed with tinnitus. Veterans with a TBI diagnosis, compared with those without a TBI diagnosis, had 3.6 times greater likelihood of rating their tinnitus-related impairment as very severe (95% CI: 2.1-6.3), and 1.5 times greater likelihood of rating their impairment as moderate/severe (95% CI: 1.0-2.4), versus none/mild. CONCLUSIONS: These findings suggest an important role of TBI in the severity of tinnitus-related functional impairment among veterans. This knowledge can help inform the integration of tinnitus management services into the care received by veterans with TBI.

Prevalence and Correlates of VA-Purchased Community Care Use Among Post-9/11-Era Veterans With Traumatic Brain Injury.

OBJECTIVE: Post-9/11-era veterans with traumatic brain injury (TBI) have greater health-related complexity than veterans overall, and may require coordinated care from TBI specialists such as those within the Department of Veterans Affairs (VA) healthcare system. With passage of the Choice and MISSION Acts, more veterans are using VA-purchased care delivered by community providers who may lack TBI training. We explored prevalence and correlates of VA-purchased care use among post-9/11 veterans with TBI. SETTING: Nationwide VA-purchased care from 2016 through 2019. PARTICIPANTS: Post-9/11-era veterans with clinician-confirmed TBI based on VA's Comprehensive TBI Evaluation (N = 65 144). DESIGN: This was a retrospective, observational study. MAIN MEASURES: Proportions of veterans who used VA-purchased care and both VA-purchased and VA-delivered outpatient care, overall and by study year. We employed multivariable logistic regression to assess associations between veterans' sociodemographic, military history, and clinical characteristics and their likelihood of using VA-purchased care from 2016 through 2019. RESULTS: Overall, 51% of veterans with TBI used VA-purchased care during the study period. Nearly all who used VA-purchased care (99%) also used VA-delivered outpatient care. Veterans' sociodemographic, military, and clinical characteristics were associated with their likelihood of using VA-purchased care. Notably, in adjusted analyses, veterans with moderate/severe TBI (vs mild), those with higher health risk scores, and those diagnosed with posttraumatic stress disorder, depression, anxiety, substance use disorders, or pain-related conditions had increased odds of using VA-purchased care. Additionally, those flagged as high risk for suicide also had higher odds of VA-purchased care use. CONCLUSIONS: Veterans with TBI with greater health-related complexity were more likely to use VA-purchased care than their less complex counterparts. The risks of potential care fragmentation across providers versus the benefits of increased access to care are unknown. Research is needed to examine health and functional outcomes among these veterans.

Harmonizing federal interagency traumatic brain injury research data to examine depression and suicide-related outcomes.

OBJECTIVE: This proof-of-concept study was conducted to establish the feasibility of compiling Federal Interagency Traumatic Brain Injury Research (FITBIR) data pertaining to depression and suicide risk, with the secondary goal of improving understanding regarding these outcomes. FITBIR is a national repository of participant-level traumatic brain injury (TBI) data designed to address methodological limitations (e.g., small sample size, heterogeneity of injuries). METHOD: FITBIR studies with TBI severity and measures related to depression and suicidal ideation were identified. Data were harmonized across relevant studies and grouped to identify "probable depression" and suicidal ideation, resulting in a large, combined sample. Rates of probable depression and suicidal ideation were described across the available studies, considering the influence of demographic and/or injury-related factors on outcomes. RESULTS: Cross-sectional studies meeting criteria included four studies with depression outcomes and two with suicidal ideation outcomes. Two studies reported data appropriate for comparative analyses on depression. Combined results suggested that approximately 71% of participants were categorized as having probable depression. Participants with a history of mild TBI had 2.54 greater odds of probable depression (95% confidence interval [1.93, 3.34]) than those without a history of TBI. CONCLUSIONS: Methods, harmonization code, and meta-databases related to TBI, probable depression, and suicidal ideation are now publicly available on the FITBIR website. Even with limited data, harmonization of FITBIR studies can serve as the basis for ongoing TBI and mental health research. Analyses will be more robust in the future as more studies with relevant outcome data are added to the FITBIR database. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Characterizing and Comparing Evidence-Based Psychotherapy Utilization Among Veterans with Co-occurring PTSD and Substance Use Disorder.

Objective: The current study sought to describe a nationally representative sample of Veterans diagnosed with co-occurring PTSD and substance use disorder (SUD) who initiated and completed evidence-based psychotherapy (EBP) for PTSD, and explored whether completion rates differed by SUD subtype. Methods: Using electronic health record data from the Veterans Health Administration (VHA) Corporate Data Warehouse, Veterans with a dual diagnosis of PTSD and SUD who initiated either Cognitive Processing Therapy (CPT) or Prolonged Exposure (PE) between January 01, 2019 and July 16, 2019 were identified (N = 2,996). Logistic analyses were employed to determine whether there were differences in EBP completion rates among Veterans with an alcohol use disorder (AUD; n = 1,383) versus all other SUDs (n = 1,613). Results: On average, Veterans were 45 years old, and identified as male, White, and non-Hispanic. Logistic regression analyses revealed there was not a significant difference between Veterans with AUD only and other SUDs in the probability of completing EBP treatment, OR = 1.02, 95% CI =0.87, 1.17, p = 0.79. Conclusions: No differences in EBP completion rates were observed between SUD subtypes, indicating that EBPs for PTSD are tolerated well for individuals with various types of SUDs and may be offered as treatment options.

Phenotyping Depression After Mild Traumatic Brain Injury: Evaluating the Impact of Multiple Injury, Gender, and Injury Context.

The chronic mental health consequences of mild traumatic brain injury (TBI) are a leading cause of disability. This is surprising given the expectation of significant recovery after mild TBI, which suggests that other injury-related factors may contribute to long-term adverse outcomes. The objective of this study was to determine how number of prior injuries, gender, and environment/context of injury may contribute to depressive symptoms after mild TBI among deployed United States service members and veterans (SMVs). Data from the Long-term Impact of Military-Relevant Brain Injury Consortium Prospective Longitudinal Study was used to assess TBI injury characteristics and depression scores previously measured on the Patient Health Questionnaire-9 (PHQ-9) among a sample of 1456 deployed SMVs. Clinical diagnosis of mild TBI was defined via a multi-step process centered on a structured face-to-face interview. Logistical and linear regressions stratified by gender and environment of injury were used to model depressive symptoms controlling for sociodemographic and combat deployment covariates. Relative to controls with no history of mild TBI (n = 280), the odds ratios (OR) for moderate/severe depression (PHQ-9 ≥ 10) were higher for SMVs with one mild TBI (n = 358) OR: 1.62 (95% confidence interval [CI] 1.09-2.40, p = 0.016) and two or more mild TBIs (n = 818) OR: 1.84 (95% CI 1.31-2.59, p < 0.001). Risk differences across groups were assessed in stratified linear models, which found that depression symptoms were elevated in those with a history of multiple mild TBIs compared with those who had a single mild TBI (p < 0.001). Combat deployment-related injuries were also associated with higher depression scores than injuries occurring in non-combat or civilian settings (p < 0.001). Increased rates of depression after mild TBI persisted in the absence of post-traumatic stress disorder. Both men and women SMVs separately exhibited significantly increased depressive symptom scores if they had had combat-related mild TBI. These results suggest that contextual information, gender, and prior injury history may influence long-term mental health outcomes among SMVs with mild TBI exposure.

Neuropsychological Correlates of PTSD and Depressive Symptom Improvement in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury.

INTRODUCTION: Mild traumatic brain injury (mTBI), depression, and PTSD are highly prevalent in post-9/11 veterans. With the comorbidity of depression and PTSD in post-9/11 veterans with mTBI histories and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. We sought to examine neuropsychological correlates of PTSD and depressive symptom improvement in veterans with a history of mTBI who received CCT. MATERIALS AND METHODS: Thirty-seven post-9/11 veterans with mTBI histories and cognitive complaints received 10 weekly 120-minute CCT group sessions. Participants completed a baseline neuropsychological assessment, including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD and depression) at baseline, post-treatment, and a 5-week follow-up. Paired samples t-tests were used to examine statistically significant changes in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson's correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores were entered as independent variables in multivariable regression analyses to examine their association with symptom change at post-treatment and follow-up. RESULTS: Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (≥17.5% score reduction), and over 20% had clinically meaningful improvement in PTSD symptoms (≥10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on Trail-Making Number-Letter Switching was also associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed that worse processing speed and worse aspects of executive functioning at baseline were associated with depressive symptom improvement at post-treatment and follow-up. CONCLUSIONS: Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve.

Inactivation of high-risk flags for suicide in the Veterans Health Administration: Association of documentation variation with suicide attempts.

Medical record high-risk flags for suicide indicate patients are receiving enhanced care and alert treating providers to patients' high-risk status. Risk of suicide mortality remains high after flag inactivation, suggesting a need to improve inactivation determinations. This study describes variation in flag inactivation documentation, examines whether documentation varies by patient or facility characteristics, and explores the association between inactivation documentation type and subsequent suicide attempts. In a national sample of veterans with a documented suicide attempt who received a high-risk flag for suicide (n = 224), medical record review was used to categorize provider documentation of the rationale and procedures for high-risk flag inactivation. Mixed-effects logistic regression models were used to examine patient and facility characteristics associated with flag inactivation documentation type and to examine the association between documentation type and subsequent suicide attempts. Flag inactivation documentation fell into one of two categories: documentation stating the patient no longer met criteria for the high-risk flag (minimal documentation; n = 98, 43.8%); and documentation that included a review of one or more criteria for high-risk flag inactivation (more than minimal documentation; n = 126, 56.3%). Flag inactivation documentation was not associated with patient or facility characteristics. Veterans with minimal documentation (vs. more than minimal) were more likely to have a suicide attempt after flag inactivation (adjusted odds ratio, AOR = 2.20; 95% CI [1.01, 4.78]; p = .046). Findings suggest a need to better understand flag inactivation procedures in place and to develop a set of standardized procedures to reduce risk of premature high-risk flag inactivation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Factors Associated with Engaging in Evidence-Based Psychotherapy During the First Year of Posttraumatic Stress Disorder Treatment Between 2017 and 2019.

To address the burden of posttraumatic stress disorder (PTSD), the Veterans Health Administration (VHA) implemented evidence-based psychotherapies (EBPs) for PTSD at all VHA medical centers. Prior investigations show EBP utilization has increased following the initial nationwide implementation. However, most patients still do not engage in EBPs and those who do often have substantial delays between diagnosis and treatment which is associated with poorer treatment outcomes. The goal of the current study is to identify patient and clinical factors associated with initiating EBP and completing a minimally adequate dose of treatment within the first year of a new PTSD diagnosis. Overall, 263,018 patients started PTSD treatment between 2017 and 2019 and 11.6% (n = 30,462) initiated EBP during their first year of treatment. Of those who initiated EBP, 32.9% (n = 10,030) received a minimally adequate dose. Older patients were less likely to initiate EBP, but more likely to receive an adequate dose when they did initiate. Black, Hispanic/Latino/a, and Pacific Islander patients' likelihood of initiating EBP was not significantly different than White patients, but these patients were less likely to receive an adequate dose. Patients with comorbid depressive disorders, bipolar disorder, psychotic disorders, or substance use disorders were less likely to initiate EBP, while patients reporting MST were more likely to initiate EBP. This study identifies several patient-level disparities that could be prioritized to increase EBP utilization. In our evaluation, most patients did not engage in EBP during their first year of PTSD treatment, which is consistent with previous evaluations of EBP utilization. Future research should focus on understanding the flow of patients from PTSD diagnosis to treatment to support effective PTSD care delivery.

Differences in rates of impairment in adults who use methamphetamine using two sets of demographically corrected norms.

Neuropsychologists can expect to meet with increasing rates of patients who use methamphetamine (MA), as MA use is on the rise, often comorbid with other substance use disorders, and frequently accompanied by changes in cognitive functioning. To detect impairment, neuropsychologists must apply the appropriate normative data according to important demographic factors such as age, sex, and education. This study involved 241 adults with and without MA dependence who were administered the Neuropsychological Assessment Battery. Given the high rates of polysubstance use among adults who use MA, we included adults with mono-dependence and poly-dependence on MA and at least one other substance. We compared the rates of adults with and without previous MA dependence classified as impaired on neurocognitive testing when using norms corrected for age, education, and sex versus norms corrected only for age. Norms corrected for age, education, and sex resulted in less frequent identification of impairment compared to norms corrected only for age, but both sets of norms appeared sufficient and similar enough to warrant their use with this population. It may be appropriate to explore the possible implications of discrepancies between education-corrected and non-education corrected sets of scores when assessing impairment in individuals who use MA.

Can mild traumatic brain injury alter cognition chronically? A LIMBIC-CENC multicenter study.

OBJECTIVE: While outcome from mild traumatic brain injury (mTBI) is generally favorable, concern remains over potential negative long-term effects, including impaired cognition. This study examined the link between cognitive performance and remote mTBIs within the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) multicenter, observational study of Veterans and service members (SMs) with combat exposure. METHOD: Baseline data of the participants passing all cognitive performance validity tests (n = 1,310) were used to conduct a cross-sectional analysis. Using multivariable regression models that adjusted for covariates, including age and estimated preexposure intellectual function, positive mTBI history groups, 1-2 lifetime mTBIs (nonrepetitive, n = 614), and 3 + lifetime mTBIs (repetitive; n = 440) were compared to TBI negative controls (n = 256) on each of the seven cognitive domains computed by averaging Z scores of prespecified component tests. Significance levels were adjusted for multiple comparisons. RESULTS: Neither of the mTBI positive groups differed from the mTBI negative control group on any of the cognitive domains in multivariable analyses. Findings were also consistently negative across sensitivity analyses (e.g., mTBIs as a continuous variable, number of blast-related mTBIs, or years since the first and last mTBI). CONCLUSIONS: Our findings demonstrate that the average veteran or SM who experienced one or more mTBIs does not have postacute objective cognitive deficits due to mTBIs alone. A holistic health care approach including comorbidity assessment is indicated for patients reporting chronic cognitive difficulties after mTBI(s), and strategies for addressing misattribution may be beneficial. Future study is recommended with longitudinal designs to assess within-subjects decline from potential neurodegeneration. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Randomized controlled trials of mind-body interventions for posttraumatic stress disorder: a systematic review.

Mind-body interventions (MBIs) include mindfulness-based interventions (MiBIs), meditation- and mantra-based interventions (MMIs), and movement-based interventions (MoBIs). These approaches have demonstrated preliminary efficacy in improving posttraumatic stress disorder (PTSD) symptoms. However, previous systematic reviews and meta-analyses have noted that this area of research is limited by inadequate comparator conditions, heterogeneity of measurement, and absence of objective outcome measures. For these reasons, an updated review of the highest-quality evidence available is warranted. We used the Agency for Healthcare Research and Quality (AHRQ)-funded evidence tables for the PTSD-Repository to identify relevant studies and assess the risk of bias as follows: The search was conducted between June 2018 and June 2022, and databases included PTSDpubs (formerly PILOTS), Ovid® MEDLINE®, Cochrane CENTRAL, Embase®, the Cumulative Index to Nursing and Allied Health Literature (CINAHL®), SCOPUS, and PsycINFO®. Twenty-six randomized controlled trials met our inclusion criteria. After identifying studies and retrieving risk of bias information from the PTSD-Repository evidence tables, we extracted additional data and synthesized the evidence. The strength of evidence was rated as low for MiBIs and MMIs, largely due to contradicting results, inconsistent use of active versus passive comparators, and high risk of bias. The strength of evidence for MoBIs was rated as moderate due to individual studies consistently favoring the intervention and a relatively large number of studies and participants. Of the 26 included studies, only two included objective outcome measures. Implications for future MBI research and clinical applications for treating PTSD are discussed.

Mild traumatic brain injury, PTSD symptom severity, and behavioral dyscontrol: a LIMBIC-CENC study.

Background: Behavioral dyscontrol occurs commonly in the general population and in United States service members and Veterans (SM/V). This condition merits special attention in SM/V, particularly in the aftermath of deployments. Military deployments frequently give rise to posttraumatic stress disorder (PTSD) and deployment-related mild TBI traumatic brain injury (TBI), potentially leading to manifestations of behavioral dyscontrol. Objective: Examine associations among PTSD symptom severity, deployment-related mild traumatic brain injury, and behavioral dyscontrol among SM/V. Design: Secondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium prospective longitudinal study among SM/V (N = 1,808). Methods: Univariable and multivariable linear regression models assessed the association and interaction effects between PTSD symptom severity, as assessed by the PTSD Checklist for the Diagnostic and Statistical Manual, 5th edition (PCL-5), and deployment-related mild TBI on behavioral dyscontrol, adjusting for demographics, pain, social support, resilience, and general self-efficacy. Results: Among the 1,808 individuals in our sample, PTSD symptom severity (B = 0.23, 95% CI: 0.22, 0.25, p < 0.001) and deployment-related mild TBI (B = 3.27, 95% CI: 2.63, 3.90, p < 0.001) were significantly associated with behavioral dyscontrol in univariable analysis. Interaction effects were significant between PTSD symptom severity and deployment mild TBI (B = -0.03, 95% CI: -0.06, -0.01, p = 0.029) in multivariable analysis, indicating that the effect of mild TBI on behavioral dyscontrol is no longer significant among those with a PCL-5 score > 22.96. Conclusion: Results indicated an association between PTSD symptom severity, deployment-related mild TBI, and behavioral dyscontrol among SM/V. Notably, the effect of deployment-related mild TBI was pronounced for individuals with lower PTSD symptom severity. Higher social support scores were associated with lower dyscontrol, emphasizing the potential for social support to be a protective factor. General self-efficacy was also associated with reduced behavioral dyscontrol.

Neuropsychological Performance and Functional Capacity Following Mild Traumatic Brain Injury in Veterans.

OBJECTIVE: To examine the relationship between neuropsychological functioning and performance-based functional capacity in veterans with a history of mild traumatic brain injury (mTBI), as well as the moderating effects of age and psychiatric symptoms on this relationship. SETTING: Three Veterans Affairs medical centers. PARTICIPANTS: One hundred nineteen Iraq/Afghanistan veterans with a history of mTBI and self-reported cognitive difficulties. DESIGN: Cross-sectional, secondary data analysis of baseline measures in a randomized controlled trial. MAIN MEASURES: The main outcome measure, functional capacity, was assessed using the objective and performance-based University of California San Diego Performance-based Skills Assessment-Brief. A global deficit score (GDS) was created as a composite score for performance on a battery of neuropsychological measures assessing domains of attention, processing speed, executive functioning, and verbal memory performance. Posttraumatic stress disorder (PTSD) symptom severity was assessed using the PTSD Checklist-Military Version, and depressive symptom severity was assessed using the Beck Depression Inventory, Second Edition. RESULTS: Bivariate analyses indicated that worse neuropsychological performance (ie, higher GDS) and greater PTSD symptom severity were associated with worse communication abilities and worse overall functional capacity. Multiple linear regressions demonstrated that GDS and PTSD symptom severity explained 9% of the variance in communication and 10% of the variance in overall functional capacity; however, GDS emerged as the only significant predictor in both regressions. Age, PTSD, and depressive symptom severity did not moderate the relationship between GDS and overall functional capacity. Performance in the verbal learning and memory domain emerged as the strongest neuropsychological predictor of communication and overall functional capacity. CONCLUSIONS: Worse neuropsychological functioning was moderately associated with worse performance-based functional capacity, even when accounting for PTSD symptom severity. Verbal learning and memory was the primary neuropsychological domain driving the relationship with functional capacity; improvement in verbal learning and memory may translate into improved functional capacity.

Formal mindfulness practice predicts reductions in PTSD symptom severity following a mindfulness-based intervention for women with co-occurring PTSD and substance use disorder.

BACKGROUND: Women with co-occurring posttraumatic stress disorder (PTSD) and substance use disorder (SUD) experience systemic barriers that place them in danger of poorer treatment outcomes. Some mindfulness-based interventions (MBIs) have demonstrated efficacy in reducing PTSD and SUD symptoms. Mindfulness practice is a core component of MBIs, thought to elicit and maintain positive behavioral change; however, no research to our knowledge has assessed the role of mindfulness practice on sustained treatment gains among women with co-occurring PTSD-SUD. Such research is necessary to better inform MBIs for dually diagnosed women. METHODS: This secondary analysis assessed whether post-intervention formal and informal mindfulness practice predicted reductions in PTSD symptoms and substance craving 6 months following an 8-session mindfulness-based relapse prevention intervention for women diagnosed with co-occurring PTSD-SUD (N = 23). Data were derived from a pilot randomized controlled trial evaluating the feasibility and preliminary efficacy of a trauma-integrated mindfulness-based relapse prevention program for women with co-occurring PTSD-SUD. RESULTS: Greater duration of formal mindfulness practice (i.e., minutes per practice) predicted reduced total PTSD symptoms ([Formula: see text] = - .670, p < .00), trauma-related avoidance ([Formula: see text] = - .564, p = .01), arousal and reactivity ([Formula: see text] = - .530, p = .02), and negative cognitions and mood ([Formula: see text] = - .780, p < .01) six months following treatment. Informal practice did not predict any outcomes. CONCLUSIONS: This research highlights the potential role of formal mindfulness practice in sustaining reductions in PTSD symptoms over time among women with co-occurring PTSD-SUD. Further study of strategies to promote ongoing formal mindfulness practice in this population following a MBI are warranted. Trial registration The parent trial was registered with ClinicalTrials.gov (Identifier: NCT03505749).

Dietary Supplementation With Branched Chain Amino Acids to Improve Sleep in Veterans With Traumatic Brain Injury: A Randomized Double-Blind Placebo-Controlled Pilot and Feasibility Trial.

Study Objectives: Traumatic brain injury (TBI) is associated with chronic sleep disturbances and cognitive impairment. Our prior preclinical work demonstrated dietary supplementation with branched chain amino acids (BCAA: leucine, isoleucine, and valine), precursors to de novo glutamate production, restored impairments in glutamate, orexin/hypocretin neurons, sleep, and memory in rodent models of TBI. This pilot study assessed the feasibility and preliminary efficacy of dietary supplementation with BCAA on sleep and cognition in Veterans with TBI. Methods: Thirty-two Veterans with TBI were prospectively enrolled in a randomized, double-blinded, placebo-controlled trial comparing BCAA (30 g, b.i.d. for 21-days) with one of two placebo arms (microcrystalline cellulose or rice protein, both 30 g, b.i.d. for 21-days). Pre- and post-intervention outcomes included sleep measures (questionnaires, daily sleep/study diaries, and wrist actigraphy), neuropsychological testing, and blood-based biomarkers related to BCAA consumption. Results: Six subjects withdrew from the study (2/group), leaving 26 remaining subjects who were highly adherent to the protocol (BCAA, 93%; rice protein, 96%; microcrystalline, 95%; actigraphy 87%). BCAA were well-tolerated with few side effects and no adverse events. BCAA significantly improved subjective insomnia symptoms and objective sleep latency and wake after sleep onset on actigraphy. Conclusion: Dietary supplementation with BCAA is a mechanism-based, promising intervention that shows feasibility, acceptability, and preliminary efficacy to treat insomnia and objective sleep disruption in Veterans with TBI. A larger scale randomized clinical trial is warranted to further evaluate the efficacy, dosing, and duration of BCAA effects on sleep and other related outcome measures in individuals with TBI. Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03990909].

Sleep quality: A common thread linking depression, post-traumatic stress, and post-concussive symptoms to biomarkers of neurodegeneration following traumatic brain injury.

OBJECTIVE: Following mild traumatic brain injury (mTBI), many individuals suffer from persistent post-concussive, depressive, post-traumatic stress, and sleep-related symptoms. Findings from self-report scales link these symptoms to biomarkers of neurodegeneration, although the underlying pathophysiology is unclear. Each linked self-report scale includes sleep items, raising the possibility that despite varied symptomology, disordered sleep may underlie these associations. To isolate sleep effects, we examined associations between post-mTBI biomarkers of neurodegeneration and symptom scales according to composite, non-sleep, and sleep components. METHODS: Plasma biomarkers and self-report scales were obtained from 143 mTBI-positive warfighters. Pearson's correlations and regression models were constructed to estimate associations between total, sleep, and non-sleep scale items with biomarker levels, and with measured sleep quality. RESULTS: Symptom severity positively correlated with biomarker levels across scales. Biomarker associations were largely unchanged when sleep items were included, excluded, or considered in isolation. Pittsburgh Sleep Quality Index demonstrated strong correlations with sleep and non-sleep items of all scales. CONCLUSION: The congruency of associations raises the possibility of a common pathophysiological process underlying differing symptomologies. Given its role in neurodegeneration and mood dysregulation, sleep physiology seems a likely candidate. Future longitudinal studies should test this hypothesis, with a focus on identifying novel sleep-related therapeutic targets.

Demographic, military, and health comorbidity variables by mild TBI and PTSD status in the LIMBIC-CENC cohort.

OBJECTIVE: To describe associations of demographic, military, and health comorbidity variables between mild traumatic brain injury (mTBI) history and posttraumatic stress disorder (PTSD) status in a sample of Former and current military personnel. SETTING: Participants recruited and tested at seven VA sites and one military training facility in the LIMBIC-CENC prospective longitudinal study (PLS), which examines the long-term mental health, neurologic, and cognitive outcomes among previously combat-deployed U.S. Service Members and Veterans (SM/Vs). PARTICIPANTS: A total of 1,540 SM/Vs with a history of combat exposure. Data were collected between 1/1/2015 through 3/31/2019. DESIGN: Cross-sectional analysis using data collected at enrollment into the longitudinal study cohort examining demographic, military, and health comorbidity variables across PTSD and mTBI subgroups. MAIN MEASURES: PTSD Checklist for DSM-5 (PCL-5), mTBI diagnostic status, Patient Health Questionnaire 9-item (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), AUDIT-C, and other self-reported demographic, military, and health comorbidity variables. RESULTS: Ten years following an index date of mTBI exposure or mid-point of military deployment, combat-exposed SM/Vs with both mTBI history and PTSD had the highest rates of depression symptoms, pain, and sleep apnea risk relative to SM/Vs without both of these conditions. SM/Vs with PTSD, irrespective of mTBI history, had high rates of obesity, sleep problems, and pain. CONCLUSION: The long-term symptom reporting and health comorbidities among SM/Vs with mTBI history and PTSD suggest that ongoing monitoring and intervention is critical for addressing symptoms and improving quality of life.

Mental health outcomes of adults hospitalized for COVID-19: A systematic review.

BACKGROUND: Patients hospitalized for COVID-19 may be at high risk of mental health (MH) disorders. This systematic review assesses MH outcomes among adults during and after hospitalization for COVID-19 and ascertains MH care utilization and resource needs. METHODS: We searched multiple medical literature databases for studies published December 2019 to March 2021. Studies of ≥ 200 participants were synthesized. One reviewer completed article selection, data abstraction and assessed study quality and strength of evidence, with verification by a second. RESULTS: Fifty articles met preliminary inclusion criteria; 19 articles that included ≥ 200 participants were synthesized. Evidence from these primarily fair-quality studies suggests many patients experience symptoms of depression (9-66%), anxiety (30-39%), and insomnia (24-40%) during and 3 months after hospitalization for COVID-19. However, patients infrequently receive a new MH disorder diagnosis 6 months after hospitalization (5% are diagnosed with a new mood disorder, 7% anxiety disorder, and 3% insomnia). Some hospitalized patients - including women and those with more severe COVID-19 - may be at higher risk of poor MH outcomes. Data on MH care utilization and resource needs are currently limited. LIMITATIONS: Most included studies were small, did not report the proportion of participants with preexisting MH disorders, and did not use comparison groups. CONCLUSIONS: While many patients experience MH symptoms after hospitalization for COVID-19, most do not go on to develop a new MH disorder. Future studies should report whether participants have preexisting MH disorders and compare patients hospitalized for COVID-19 to patients hospitalized for other causes.

Opioid and Sedative-Hypnotic Prescriptions Among Post-9/11 Veteran VA Users Nationwide With Traumatic Brain Injury, 2012-2020.

OBJECTIVE: Many post-9/11 Veterans have received Department of Veterans Affairs (VA) healthcare for traumatic brain injury (TBI). Pain conditions are prevalent among these patients and are often managed with opioid analgesics. Opioids may impose unique risks to Veterans with a history of TBI, especially when combined with other psychotropic medications. We examined receipt of opioid and sedative-hypnotic prescriptions among post-9/11 Veterans with TBI who received VA care nationally between 2012 and 2020. SETTING: Nationwide VA outpatient care. PARTICIPANTS: Veterans with, versus without, clinician-confirmed TBI based on the VA's Comprehensive TBI Evaluation (CTBIE) were followed up for subsequent years in which they received VA care. DESIGN: A historical cohort study. MAIN MEASURES: Proportions of Veterans who received opioid, benzodiazepine, and nonbenzodiazepine sedative-hypnotic prescriptions were compared by CTBIE outcome (TBI yes/no) and by year; overlaps between medication classes, long-term opioid therapy, and high-dose opioid therapy were also examined. Among those with confirmed TBI, logistic regression was used to examine associations between veteran characteristics and likelihood of these potentially high-risk opioid use outcomes. RESULTS: Among 69 752 Veterans with clinician-confirmed TBI, 26.9% subsequently received opioids. The prevalence receiving opioids each year increased from 2012 (16.7%) to 2014 (17.7%), and then decreased each of the following years through 2020 (5.8%). Among Veterans with TBI who received opioids, large proportions also received benzodiazepine (30.1%) and nonbenzodiazepine (36.0%) sedative-hypnotic prescriptions; these proportions also decreased in recent years. In both bivariable and multivariable regression models, Veterans' demographic, TBI, and clinical characteristics were associated with likelihood of potentially high-risk opioid use. CONCLUSIONS: VA opioid prescribing to Veterans with TBI has decreased in recent years but remains an important source of risk, particularly when considering coprescriptions of sedative-hypnotic medication. Understanding patterns of psychotropic prescription use among Veterans with TBI can highlight important healthcare and rehabilitation needs in this large patient cohort.

Change in Learning and Memory Partially Mediates Effects of Compensatory Cognitive Training on Self-Reported Cognitive Symptoms.

OBJECTIVE: To examine associations among compensatory cognitive training (CCT), objective cognitive functioning, and self-reported cognitive symptoms. We examined whether change in objective cognitive functioning associated with participation in CCT at 10-week follow-up mediates change in self-reported cognitive symptoms associated with CCT at 15-week follow-up. SETTING: Three VA outpatient mental health clinics. PARTICIPANTS: Veterans with a history of mild traumatic brain injury who reported cognitive deficits. DESIGN: Randomized controlled trial post hoc causal mediation analysis. MAIN MEASURES: Self-reported cognitive symptoms were measured by the Prospective-Retrospective Memory Questionnaire and the Multiple Sclerosis Neuropsychological Screening Questionnaire. Objective cognitive functioning was measured using a battery of neuropsychological tests. RESULTS: Improvement on the Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall test mediated the association between participation in CCT and decrease in the Prospective-Retrospective Memory Questionnaire total score. Improvement on the HVLT-R Total Recall and HVLT-R Delayed Recall tests both meditated the association between participation in CCT and decrease in the Multiple Sclerosis Neuropsychological Screening Questionnaire total score. No other measures of objective cognitive functioning were significant mediators. CONCLUSION: Patients' perceptions of cognitive symptom improvement due to CCT are partially mediated by learning and memory, though these subjective improvements occur regardless of other changes in objective cognitive functioning associated with CCT.