Neural substrates of symptoms of depression following concussion in male athletes with persisting postconcussion symptoms

Context: Depressed mood is frequently reported by individuals who have sustained cerebral concussion but little is known about the nature of this alteration in mood state. Objective: To investigate whether the symptoms of depression reflect an ongoing pathophysiological change following concussion. Design: Cohort study with male athletes using functional and structural neuroimaging. Setting: Hospital laboratory and imaging facility. Participants: Fifty-six male athletes with and without concussion were divided into (1) a no depression symptom, concussed group, (2) a mild depression symptom, concussed group, (3) a moderate depression symptom, concussed group, and (4) a healthy control group. Interventions: All athletes filled out a postconcussive symptoms checklist and the Beck Depression Inventory II and underwent a magnetic resonance imaging session, which included T1, T2, and fluid-attenuated inversion recovery sequences, as well as functional magnetic resonance imaging (fMRI), during which they performed a working memory task. Main Outcome Measures: (1) Behavioral: response speed and accuracy on the working memory task performed during the fMRI session; (2) functional imaging: brain activation patterns associated with the working memory task obtained using blood oxygen level dependent fMRI; and (3) structural imaging: voxel-based morphometry examining gray matter concentration. Results: (1) Behavioral: there was no performance difference between the groups; and (2) imaging: athletes with concussion with depression symptoms showed reduced activation in the dorsolateral prefrontal cortex and striatum and attenuated deactivation in medial frontal and temporal regions. The severity of symptoms of depression correlated with neural responses in brain areas that are implicated in major depression. Voxel-based morphometry confirmed gray matter loss in these areas. Conclusions: The results suggest that depressed mood following a concussion may reflect an underlying pathophysiology consistent with a limbic-frontal model of depression. Given that depression is associated with considerable functional disability, this finding has important clinical implications for the management of individuals with a cerebral concussion.