Depressive symptoms and white matter dysfunction in retired NFL players with concussion history

Department of Neurology and Neurotherapeutics (C.M.C., J.H., K.B.W.), University of Texas Southwestern Medical Center, Dallas
Neurology (Impact Factor: 8.29). 05/2013; 81(1). DOI: 10.1212/WNL.0b013e318299ccf8
Source: PubMed


To determine whether correlates of white matter integrity can provide general as well as specific insight into the chronic effects of head injury coupled with depression symptom expression in professional football players.

We studied 26 retired National Football League (NFL) athletes who underwent diffusion tensor imaging (DTI) scanning. Depressive symptom severity was measured using the Beck Depression Inventory II (BDI-II) including affective, cognitive, and somatic subfactor scores (Buckley 3-factor model). Fractional anisotropy (FA) maps were processed using tract-based spatial statistics from FSL. Correlations between FA and BDI-II scores were assessed using both voxel-wise and region of interest (ROI) techniques, with ROIs that corresponded to white matter tracts. Tracts demonstrating significant correlations were further evaluated using a receiver operating characteristic curve that utilized the mean FA to distinguish depressed from nondepressed subjects.

Voxel-wise analysis identified widely distributed voxels that negatively correlated with total BDI-II and cognitive and somatic subfactors, with voxels correlating with the affective component (p < 0.05 corrected) localized to frontal regions. Four tract ROIs negatively correlated (p < 0.01) with total BDI-II: forceps minor, right frontal aslant tract, right uncinate fasciculus, and left superior longitudinal fasciculus. FA of the forceps minor differentiated depressed from nondepressed athletes with 100% sensitivity and 95% specificity.

Depressive symptoms in retired NFL athletes correlate negatively with FA using either an unbiased voxel-wise or an ROI-based, tract-wise approach. DTI is a promising biomarker for depression in this population.

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Available from: Jeremy F Strain, Mar 24, 2014
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    • "Therefore, whole-brain white matter anomalies patterns affecting specific tracts can be related to particular cognitive/motor impairments in clinical populations. Multiple groups trying to uncover the nature of acute and chronic symptoms in concussed athletes have applied this technique (Zhang et al., 2010; Cubon et al., 2011; Koerte et al., 2012; Chamard et al., 2013; Hart et al., 2013; Strain et al., 2013) or older techniques (Zhang et al., 2003, 2006; Chappell et al., 2006; Henry et al., 2011; Bazarian et al., 2012; Marchi et al., 2013; Virji-Babul et al., 2013). Diffuse anomalies during the acute and sub-acute periods are described in most cases along various major interhemispheric, associative, and projection fibre tracts, although no consistent spatial pattern of injury seems to emerge from those studies (Gardner et al., 2012). "
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    ABSTRACT: Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.
    Full-text · Article · Sep 2014 · Brain
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    • "mTBI cases constitute approximately 85% of reported TBI cases [4], and the incidence of MD after mTBI is reported to range from 10% to 77% [17]. Our group and others have found that white matter integrity was compromised in a number of regions in patients who developed MD after mTBI [5] [6] [7] [8]. Those regions included the dorsolateral prefrontal cortex (DLPFC), CC, nucleus accumbens, and temporo-parietal regions [5]. "
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    ABSTRACT: Previous research suggests that many people who sustain a traumatic brain injury (TBI), even of the mild form, will develop major depression (MD). We previously reported white matter integrity differences between those who did and did not develop MD after mild TBI. In this current paper, we aimed to investigate whether there were also volumetric differences between these groups, as suggested by previous volumetric studies in mild TBI populations. A sample of TBI-with-MD subjects (N = 14), TBI-without-MD subjects (N = 12), MD-without-TBI (N = 26) and control subjects (no TBI or MD, N = 23), received structural MRI brain scans. T1-weighted data were analysed using the Freesurfer software package which produces automated volumetric results. The findings of this study indicate that (1) TBI patients who develop MD have reduced volume in temporal, parietal and lingual regions compared to TBI patients who do not develop MD, and (2) MD patients with a history of TBI have decreased volume in the temporal region compared to those who had MD but without a history of TBI. We also found that more severe MD in those with TBI-with-MD significantly correlated with reduced volume in anterior cingulate, temporal lobe and insula. These findings suggest that volumetric reduction to specific regions, including parietal, temporal and occipital lobes, after a mild TBI may underlie the susceptibility of these patients developing major depression, in addition to altered white matter integrity.
    Full-text · Article · Sep 2014 · Behavioural Brain Research
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    ABSTRACT: Concussion has been in the medical lexicon since Hippocrates,(1) and widespread viewing of sports concussion is now commonplace. This mildest form of traumatic brain injury (TBI) has obvious acute effects, but motor symptoms seem to abate quickly as the concussed player leaves the contest. The prompt return to baseline in most sports concussions could be considered as evidence for the transient nature of the injury, with the brain's homeostatic equilibrium temporarily disrupted and then restored, but this view may be changing. With 1.6-3.8 million sports-related concussions annually in the United States (, the possible long-term consequences of concussion clearly merit attention.
    No preview · Article · May 2013 · Neurology
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