Shannon B. Juengst

Exploratory associations with tumor necrosis factor-α, disinhibition and suicidal endorsement after traumatic brain injury.

PURPOSE To examine the relationship of Tumor Necrosis Factor (TNF)-α to disinhibition and suicidal endorsement after traumatic brain injury (TBI). PARTICIPANTS Adults with moderate to severe TBI (acute serum levels: n=48, n=543 samples; acute CSF levels: n=37, n=389 samples; chronic serum levels: n=48, n=326 samples). MAIN MEASURES TNFα levels (CSF, Serum) from time of injury to 12 months post-injury; Frontal Systems Behavior Scale - Disinhibition Subscale at 6 and 12 months post-injury; Patient Health Questionnaire at 6 and 12 months post-injury. RESULTS Participants with TBI had significantly higher CSF and serum TNFα levels than healthy controls (p<0.05). Acute and chronic serum TNFα was significantly associated with disinhibition at 6 months post-injury (p=0.009, p=0.029 respectively), and 6 month disinhibition was associated with suicidal endorsement at both 6 and 12 months (p=0.045, p=0.033 respectively) and disinhibition at 12 months post-injury (p<0.001). CONCLUSION These preliminary data suggest a biological to behavioral pathway of suicidality after TBI, from TNFα to disinhibition to suicidal endorsement. Future investigation is warranted to validate these findings and clarify what biological mechanisms might underlie these relationships.

Unique Contribution of Fatigue to Disability in Community-Dwelling Adults With Traumatic Brain Injury

OBJECTIVE To examine the unique contribution of fatigue to self-reported disability in community-dwelling adults with traumatic brain injury (TBI). DESIGN A cross-sectional cohort design. SETTING Community dwellings. PARTICIPANTS Adults (N=50) with a history of mild to severe TBI were assessed. INTERVENTION Not applicable. MAIN OUTCOME MEASURES This study assessed the contribution of fatigue (Modified Fatigue Impact Scale) to disability (Mayo-Portland Adaptability Inventory), controlling for executive functions (Frontal Systems Behavior Scale), depression status (major depression in partial remission/current major depression/depressive symptoms or no history of depression), and initial injury severity (uncomplicated mild, complicated mild, moderate, or severe). RESULTS Fatigue was found to contribute uniquely to the variance in self-reported disability (β=.47, P<.001) after controlling for injury severity, executive functions, and depression status. The overall model was significant (F(4,45)=17.32, P<.001) and explained 61% of the variance in self-reported disability, with fatigue alone accounting for 12% of the variance in self-reported disability (F(1,45)=13.97, P<.001). CONCLUSIONS Fatigue contributes uniquely to disability status among community-dwelling adults with chronic TBI, independent of injury severity, executive functions, and depression. Addressing fatigue through targeted interventions may help to improve self-perceived disability in this population.

Alterations in the hemodynamic response function in cognitively impaired HIV/AIDS subjects

Functional magnetic resonance imaging (fMRI) has revealed much about altered CNS function in HIV/AIDS. In this study, we compared the blood oxygen level dependent hemodynamic response function (BOLD HRF) signal in HIV/AIDS and control subjects as a necessary pre-condition for fMRI studies of higher level cognitive function. Using event-related fMRI, subjects performed a simple sensory-motor activity allowing the measurement of the BOLD HRF in the precentral gyrus. There were no significant differences in the HRF when viewed as a function of age, hemisphere, or HIV serostatus. However, significant results were found after dividing the subjects by NIMH impairment classifications. There were 16 control subjects, 19 Normal/Asymptomatic Neuropsychological Impairment (ANI), and 11 Minor Neurocognitive Disorder (MNCD)/HIV-Associated Dementia (HAD) subjects. The HRF of MNCD/HAD subjects did not return to baseline after 16s, suggesting subtle alterations in neuronal function, which may affect event-related fMRI studies.

Preliminary associations between brain derived neurotrophic factor, memory impairment, functional cognition, and depressive symptoms following severe TBI

Background. Traumatic brain injury (TBI) often leads to mood and cognitive complications, affecting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective. To evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods. Participants with TBI (n = 113) were evaluated for PTD (Patient Health Questionnaire-9 [PHQ-9]), cognitive impairment (cognitive composite score), and functional cognition (Functional Independence Measure–Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid and serum at 0 to 6 days postinjury and in serum at 6 and 12 months postinjury. Results. Serum BDNF was reduced after TBI versus controls at all time points. Acute serum BDNF positively correlated with memory composites (6 months: r = 0.43, P = .019, n = 30; 12 months: r = 0.53, P = .005, n = 26) and FIM-Memory scores (6 months: r = 0.35, P = .019, n = 45; 12 months: r = 0.38, P = .018, n = 38). Acute serum BDNF negatively correlated with 12-month PHQ-9 scores (r = −0.38; P = .044; n = 29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (P = .07) and correlated with PHQ-9 scores (r = −0.41; P = .019; n = 32). Conclusions. Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI.

Trajectories of Life Satisfaction After Traumatic Brain Injury: Influence of Life Roles, Age, Cognitive Disability, and Depressive Symptoms

OBJECTIVES (a) Identify life satisfaction trajectories after moderate to severe traumatic brain injury (TBI); (b) establish a predictive model for these trajectories across the first 5 years postinjury; and (c) describe differences in these life satisfaction trajectory groups, focusing on age, depressive symptoms, disability, and participation in specific life roles. RESEARCH METHOD Analysis of the longitudinal TBI Model Systems National Database was performed on data collected prospectively at 1-, 2-, and 5-years post-TBI. Participants (n = 3,012) had a moderate to severe TBI and were 16 years old and older. RESULTS Four life satisfaction trajectories were identified across the first 5 years postinjury, including: stable satisfaction, initial satisfaction declining, initial dissatisfaction improving, and stable dissatisfaction. Age, depressive symptoms, cognitive disability, and life role participation as a worker, leisure participant, and/ or religious participant at 1-year postinjury significantly predicted trajectory group membership. Life role participation and depressive symptoms were strong predictors of life satisfaction trajectories across the first 5 years post-TBI. CONCLUSIONS The previously documented loss of life roles and prevalence of depression after a moderate to severe TBI make this a vulnerable population for whom low or declining life satisfaction is a particularly high risk. Examining individual life role participation may help to identify relevant foci for community-based rehabilitation interventions or supports.

Strategy Training Shows Promise for Addressing Disability in the First 6 Months After Stroke

Background. Cognitive impairments occur frequently after stroke and contribute to significant disability. Strategy training shows promise but has not been examined in the acute phase of recovery. Objective. We conducted a single-blind randomized pilot study estimating the effect of strategy training, relative to reflective listening (attention control), for reducing disability and executive cognitive impairments. Methods. Thirty participants with acute stroke who were enrolled in inpatient rehabilitation and had cognitive impairments were randomized to receive strategy training (n = 15, 10 sessions as adjunct to usual inpatient rehabilitation) or reflective listening (n = 15, same dose). The Functional Independence Measure assessed disability at baseline, rehabilitation discharge, 3, and 6 months. The Color Word Interference Test of the Delis–Kaplan Executive Function System assessed selected executive cognitive impairments (inhibition, flexibility) at baseline, 3, and 6 months. Results. Changes in Functional Independence Measure scores for the 2 groups over 6 months showed significant effects of group (F1,27 = 9.25, P = .005), time (F3,74 = 96.00, P < .001), and group * time interactions (F3,74 = 4.37, P < .007) after controlling for baseline differences in stroke severity (F1,27 = 6.74, P = .015). Color Word Interference Inhibition scores showed significant effects of group (F1,26 = 6.50, P = .017) and time (F2,34 = 4.74, P = .015), but the group * time interaction was not significant (F2,34 = 2.55, P = .093). Color Word Interference Cognitive Flexibility scores showed significant effects of group (F1,26 = 23.41, P < .001), time (F2,34 = 12.77, P < .001), and group * time interactions (F2,34 = 7.83, P < .002). Interaction effects suggested greater improvements were associated with strategy training. Conclusions. Strategy training shows promise for addressing disability in the first 6 months after stroke. Lessons from this pilot study may inform future clinical trials.

Pilot feasibility of an mHealth system for conducting ecological momentary assessment of mood-related symptoms following traumatic brain injury.

Abstract Objective: This study assessed pilot feasibility and validity of a mobile health (mHealth) system for tracking mood-related symptoms after traumatic brain injury (TBI). Design: A prospective, repeated measures design was used to assess compliance with daily ecological momentary assessments (EMA) conducted via a smartphone application over an 8-week period. Methods: An mHealth system was developed specifically for individuals with TBI and utilized previously validated tools for depressive and anxiety symptoms (Patient Health Questionnaire-9, Generalized Anxiety Disorder-7). Feasibility was assessed in 20 community-dwelling adults with TBI via an assessment of compliance, satisfaction and usability of the smartphone applications. The authors also developed and implemented a clinical patient safety management mechanism for those endorsing suicidality. Results: Participants correctly completed 73.4% of all scheduled assessments, demonstrating good compliance. Daily assessments took <2 minutes to complete. Participants reported high satisfaction with smartphone applications (6.3 of 7) and found them easy to use (6.2 of 7). Comparison of assessments obtained via telephone-based interview and EMA demonstrated high correlations (r = 0.81–0.97), supporting the validity of conducting these assessments via smartphone application in this population. Conclusions: EMA conducted via smartphone demonstrates initial feasibility among adults with TBI and presents numerous opportunities for long-term monitoring of mood-related symptoms in real-world settings.

COMT and ANKK1 Genetics Interact With Depression to Influence Behavior Following Severe TBI An Initial Assessment

Objective. Genetic variations in the dopamine (DA) system are associated with cortical-striatal behavior in multiple populations. This study assessed associations of functional polymorphisms in the ankyrin repeat and kinase domain (ANKK1; Taq1a) and catechol-O-methyltransferase (COMT; Val158Met) genes with behavioral dysfunction following traumatic brain injury (TBI). Participants. This was a prospective study of 90 survivors of severe TBI recruited from a level 1 trauma center. Main measures. The Frontal Systems Behavior Scale, a self- or family report questionnaire evaluating behavior associated with frontal lobe dysfunction, was completed 6 and 12 months postinjury. Depression was measured concurrently with the Patient Health Questionnaire-9. Study participants were genotyped for Val158Met and Taq1a polymorphisms. Results. No statistically significant behavioral differences were observed by Taq1a or Val158Met genotype alone. At 12 months, among those with depression, Met homozygotes (Val158Met) self-reported worse behavior than Val carriers (P = .015), and A2 homozygotes (Taq1a) self-reported worse behavior than A1 carriers (P = .028) in bivariable analysis. Multivariable models suggest an interaction between depression and genetic variation with behavior at 12 months post-TBI, and descriptive analysis suggests that carriage of both risk alleles may contribute to worse behavioral performance than carriage of either risk allele alone. Conclusion. In the context of depression, Val158Met and Taq1a polymorphisms are individually associated with behavioral dysfunction 12 months following severe TBI, with preliminary evidence suggesting cumulative, or perhaps epistatic, effects of COMT and ANKK1 on behavioral dysfunction.

Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury.

Introduction: Traumatic brain injury (TBI) frequently results in impaired cognition, a function that can be modulated by monoaminergic signaling. Genetic variation among monoaminergic genes may affect post-TBI cognitive performance. The vesicular monoamine transporter-2 (VMAT2) gene may be a novel source of genetic variation important for cognitive outcomes post-TBI given VMAT2s role in monoaminergic neurotransmission. Objective: To evaluate associations between VMAT2 variability and cognitive outcomes post-TBI. Methods: We evaluated 136 white adults with severe TBI for variation in VMAT2 using a tagging single nucleotide polymorphism (tSNP) approach (rs363223, rs363226, rs363251, and rs363341). We show genetic variation interacts with assessed cognitive impairment (cognitive composite [Comp-Cog] T-scores) to influence functional cognition (functional independence measure cognitive [FIM-Cog] subscale] 6 and 12 months postinjury. Results: Multivariate analyses at 6 months postinjury showed rs363226 genotype was associated with Comp-Cog (P = .040) and interacted with Comp-Cog to influence functional cognition (P < .001). G-homozygotes had the largest cognitive impairment, and their cognitive impairment had the greatest adverse effect on functional cognition. Discussion: We provide the first evidence that genetic variation within VMAT2 is associated with cognitive outcomes after TBI. Further work is needed to validate this finding and elucidate mechanisms by which genetic variation affects monoaminergic signaling, mediating differences in cognitive outcomes.

Brief report of affective state and depression status after traumatic brain injury.

OBJECTIVE To examine the relationship between affective state (positive and negative affect) and depression status among adults with chronic traumatic brain injury (TBI). RESEARCH METHOD This is a cross-sectional cohort study of community-dwelling adults with chronic TBI (n = 64) that assesses the relationship between affective state (positive and negative affect), using the Positive and Negative Affect Schedule (PANAS), and depression status, categorized as no depression, history of depressive episode, and current depressive episode, using the Primary Care Evaluation of Mental Disorders (PRIME-MD). RESULTS Affective state differed significantly across depression status groups for both positive affect (F (2, 61) = 5.10, p = .009) and negative affect (F ( 2, 61) = 8.19, p = .001). Participants with no depression reported higher positive affect (M = 35.67, SD = 9.08) than those with a current depressive episode (M = 27.64, SD = 8.59, p = .007) and lower negative affect (M = 14.52, SD = 5.08) than those with a history of a depressive episode (M = 20.21, SD = 5.08, p = .006) and those with a current depressive episode (M = 22.29, SD = 6.21, p = .001). CONCLUSIONS Poor affective state, including both low positive affect and high negative affect, is associated with depression diagnosis. High negative affect is present, even in the absence of a current depressive episode, after TBI. These data highlight the need to assess affective state in addition to screening for mood disorders among adults with chronic TBI.