Risky alcohol use predicts temporal mismatch negativity impairments in young people with bipolar disorder

Alcohol misuse in bipolar disorder (BD) has a negative impact on illness progression. The NMDA/glutamatergic system is implicated in BD pathophysiology and is critically involved in the effects of alcohol on the brain. Mismatch negativity (MMN) is purported to reflect NMDA receptor output, providing a measure for investigating this association. Forty-two patients and 34 controls (16-30 years) were split into low and high-risk drinkers (based on the Alcohol Use Disorders Identification Test) and underwent a two-tone passive auditory oddball, duration deviant MMN paradigm. Multiple regression models revealed risky drinking and BD diagnosis were predictors of impaired temporal MMN. Potentially reflecting an additive effect of alcohol on a perturbed NMDA/glutamatergic system in BD, these findings highlight alcohol as both a modifiable risk factor of neurobiological impairments and as a potential confounder in MMN studies. Given the increasing use of glutamatergic agents for BD treatment, this finding is important clinically.