Acute Inflammatory Biomarker Profiles Predict Depression Risk Following Moderate to Severe Traumatic Brain Injury

Juengst, Shannon B.; Kumar, Raj G.; Failla, Michelle D.; Goyal, Arun; Wagner, Amy K.

doi:10.1097/htr.0000000000000031

Cited by 79 publications

(75 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the candidate inflammatory markers not included in the ILS, IL-12 is modulated by neurotransmitters like epinephrine and norepinephrine to a much greater degree compared to cortisol (Elenkov, 2008). Further, our previously published work suggests that CSF IL-4, IL-7, and IL-12 are not elevated above controls (Juengst, et al 2014). IL-7 has some capacity for involvement with autoimmunity (Dooms, 2013; Wang et al, 2013) without much yet known about its potential function in TBI.…”

Section: Discussionmentioning

confidence: 79%

“…IL-7 has some capacity for involvement with autoimmunity (Dooms, 2013; Wang et al, 2013) without much yet known about its potential function in TBI. IL-5 is predominantly synthesized by eosinophils and mast cells (Yu et al, 2014), with no known specific functioning in the context of clinical TBI (Kumar et al, 2014; Juengst et al, 2014; Helmy et al, 2011). While sVCAM was associated with cortisol TRAJ membership, there was no association with outcome.…”

Section: Discussionmentioning

confidence: 99%

“…For the purposes of this analysis, we used quartiles in order to simultaneously compare several markers without losing interpretability by log-transforming the data (Grund and Sabin, 2010). Several other clinical research studies have generated similar aggregate scores to evaluate inflammatory load by establishing 1) a cut-point above and below the 75 th percentile (Andaluz-Ojeda et al, 2012; Correia et al, 2010; Juengst et al 2014), 2) cut-points below the 25 th , between 25 th –75 th percentile, and greater than 75 th percentile (Wakelkamp et al, 2003; Boelen et al, 1995), or 3) quartiles (Kumar et al 2014). …”

Section: Methodsmentioning

confidence: 99%

“…Therefore, recent research has begun to examine biomarker profiles to characterize unique injury responses (Jain, 2008). At present, research suggests that both inflammatory markers and hormones may serve as reliable indicators of acute injury pathology and outcome, findings that may eventually aid in the development of individualized treatment plans (Dash et al, 2010; Kochanek et al, 2008; Wagner et al, 2011; Santarsieri et al, 2014; Juengst et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Variable neuroendocrine–immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury

Santarsieri

Kumar

Kochanek

et al. 2015

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0–6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). Group-based trajectory analysis (TRAJ) delineated subpopulations with similar longitudinal CSF cortisol profiles (high vs. low cortisol). Glasgow Outcome Scale (GOS) scores at 6 months served as the primary outcome measure reflecting global outcome. Inflammatory markers that displayed significant bivariate associations with both GOS and cortisol TRAJ (interleukin [IL]-6, IL-10, soluble Fas [sFas], soluble intracellular adhesion molecule [sICAM]-1, and tumor necrosis factor alpha [TNF]-α) were used to generate a cumulative inflammatory load score (ILS). Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS effects on outcome (indirect effect estimate= −0.253, 95% CI (−0.481, −0.025), p=0.03). Correlational analysis between mean cortisol levels and ILS were examined separately within each cortisol TRAJ group and by outcome. Within the low cortisol TRAJ group, subjects with unfavorable 6-month outcome displayed a negative correlation between ILS and mean cortisol (r=−0.562, p=0.045). Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group displayed a positive correlation between ILS and mean cortisol (r=0.391, p=0.006). Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of neuroendocrine-immune dysfunction differs between cortisol TRAJ groups. These results present a novel biomarker-based index from which to discriminate outcome and emphasize the need for evaluating tailored treatments targeting inflammation early after injury.

show abstract

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Variable neuroendocrine–immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury

Santarsieri

Kumar

Kochanek

et al. 2015

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

show abstract

“…Elevations in sICAM-1 have further been observed in patients with chronic stress as a risk factor for both immune activation and depressive mood changes [11]. Finally, higher sICAM-1 levels in the cerebrospinal fluid were very recently shown to be predictive for depression in individuals with traumatic brain injuries [12]. Taken together, ICAM-1 might be involved in the pathophysiology of vascular- and immune-associated mood changes.…”

Section: Introductionmentioning

confidence: 99%

Soluble Intracellular Adhesion Molecule-1 in Patients with Unipolar or Bipolar Affective Disorders: Results from a Pilot Trial

et al. 2016

View full text Add to dashboard Cite

Background: Immunological and vascular markers may play a role in the pathophysiology of mood disorders and mood changes. Aim: To test whether the cell adhesion molecule soluble intracellular adhesion molecule-1 (sICAM-1) may serve as a biomarker for patients with unipolar or bipolar affective disorders when compared to a healthy control group, and whether sICAM-1 blood levels change during different mood states. Methods: sICAM-1 serum concentrations were compared between 20 healthy controls and 48 patients with affective disorders (unipolar, bipolar II and bipolar I disorder) during different mood states (euthymic mood state, depression or mania). Results: When compared to healthy controls, patients with affective disorders had significantly higher sICAM-1 levels during the euthymic state (p = 0.015). Differences became more pronounced during depression (p = 0.013). When unipolar and bipolar patients were analyzed separately, unipolar patients significantly differed from controls during the euthymic and depressive mood state, while bipolar II patients showed a trend towards higher sICAM-1 levels during depression. Patients with bipolar I disorders had significantly higher sICAM-1 levels during manic states when compared to controls (p = 0.007). Conclusions: sICAM-1 elevation in unipolar and bipolar patients, independent of mood changes, might support the hypothesis of chronic immune activation and endothelial dysfunction in patients with affective disorders.

show abstract

Investigating whole‐brain metabolite abnormalities in the chronic stages of moderate or severe traumatic brain injury

Lin

Mueller

Campbell

et al. 2021

PM&R

View full text Add to dashboard Cite

Background: Evidence suggests that neurometabolic abnormalities can persist after traumatic brain injury (TBI) and drive clinical symptoms such as fatigue and cognitive disruption. Magnetic resonance spectroscopy has been used to investigate metabolite abnormalities following TBI, but few studies have obtained data beyond the subacute stage or over large brain regions. Objective: To measure whole-brain metabolites in chronic stages of TBI. Design: Observational study. Setting: University. Participants: Eleven men with a moderate or severe TBI more than 12 months prior and 10 age-matched healthy controls completed whole-brain spectroscopic imaging. Main Measures: Ratios of N-acetylaspartate (NAA), choline (CHO), and myoinositol (MI) to creatine (CR) were measured in whole-brain gray and white matter as well as 64 brain regions of interest. Arterial spin labeling (ASL) data were also collected to investigate whether metabolite abnormalities were accompanied by differences in cerebral perfusion. Results: There were no differences in metabolite ratios within whole-brain gray and white matter regions of interest (ROIs). Linear regression showed lower NAA/CR in the white matter of the left occipital lobe but higher NAA/CR in the gray matter of the left parietal lobe. Metabolite abnormalities were observed in several brain regions in the TBI group including the corpus callosum, putamen, and posterior cingulate. However, none of the findings survived correction for multiple comparison. There were no differences in cerebral blood flow between patients and controls. Conclusion: Higher MI/CR may indicate ongoing gliosis, and it has been suggested that low CHO/CR at chronic time points may indicate cell death or lack of healthy turnover and repair. However, with the small sample size of this study, we caution against the over interpretation of our results. None of the findings within ROIs survived correction for multiple comparison. Thus, they may be considered possible avenues for future research in this area.

show abstract

Acute Inflammatory Biomarker Profiles Predict Depression Risk Following Moderate to Severe Traumatic Brain Injury

Cited by 79 publications

References 12 publications

Variable neuroendocrine–immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury

Variable neuroendocrine–immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury

Soluble Intracellular Adhesion Molecule-1 in Patients with Unipolar or Bipolar Affective Disorders: Results from a Pilot Trial

Investigating whole‐brain metabolite abnormalities in the chronic stages of moderate or severe traumatic brain injury

Contact Info

Product

Resources

About