Context: Alcohol abuse and/or dependence (AA/D) and mood disturbance are co-occurring conditions among patients who have had a traumatic brain injury (TBI). However, the relationship between these disorders has not been extensively studied.Objective: To examine the relationship of AA/D and post-TBI mood disorders and the effect of these conditions on psychosocial outcome.Design: Prospective, case-control surveillance study conducted during the first year following trauma.Settings: University hospital level I trauma centers and specialized rehabilitation units.Patients: One hundred fifty-eight TBI patients with closed head injury with and without a history of AA/D.Methods: We prospectively compared psychiatric, neuropsychological, and psychosocial outcomes among the patients, who were evaluated at baseline and at 3, 6, and 12 months after trauma. Psychiatric diagnosis was made using a structured clinical interview and DSM-IV criteria. Neuropsychological testing results and quantitative magnetic resonance images were obtained at the 3-month follow-up.Results: A history of AA/D was significantly more frequent among patients who developed mood disorders during the first year following TBI. There was also a significantly higher frequency of mood disorders among patients with alcohol abuse relapse. Patients with a history of AA/D had significantly reduced frontal gray matter volumes than did patients without a history of alcohol abuse. in addition, patients who resumed alcohol abuse had decreased medial frontal gray matter volumes and impaired performance in executive tasks. Both AA/D and mood disorders following TBI were associated with a poor vocational outcome.Conclusions: Previous alcohol abuse increases the risk of developing mood disorders after TBI, and emotional disturbance, in turn, increases the risk of alcohol abuse relapse. Alcohol's neurotoxic effects and TBI likely interact to produce greater disruption of the neural circuits that modulate reward, mood, and executive function. Patients with a history of AA/D who also developed mood disorders following TBI had major difficulties resuming a productive life.