The N-Methyl-D-Aspartate Receptor as a Neurobiological Intersection Between Bipolar Disorder and Alcohol Use: A Longitudinal Mismatch Negativity Study

BACKGROUND: Comorbid risky alcohol use in bipolar disorder (BD) is recognized for its high prevalence and clinical relevance, though understanding of its neurobiological underpinning is limited. The N-methyl-D-aspartate (NMDA) receptor has recognized alterations in BD and is a major site of ethanol’s effects in the brain. The present study aimed to examine the NMDA receptor system in adolescents and young adults with BD by evaluating the longitudinal changes in a robust marker of NMDA function, mismatch negativity (MMN), in relation to changes in alcohol use patterns. METHODS: Forty-six BD patients (aged 16–30) were recruited at baseline and 59% (n = 27) returned for follow-up 17.9 +/- 7.3 months later. At both time-points a two-tone, passive, duration-deviant MMN paradigm was conducted and alcohol measures were collected. Pearson’s correlations were performed between changes in MMN amplitudes and changes in alcohol use. Multiple regression was used to assess whether MMN amplitudes at baseline could predict alcohol use at follow-up. RESULTS: Reduction in risky drinking patterns was associated with increased temporal MMN and decreased fronto-central MMN. Larger temporal MMN at baseline was a significant predictor of greater alcohol use at follow-up. CONCLUSIONS: Results suggest risky alcohol use in BD may further compound pre-existing NMDA receptor abnormalities and, importantly, reducing alcohol use early in stages of illness is associated with changes in MMN. This highlights the importance of monitoring alcohol use from first presentation. In addition, preliminary results present an exciting potential for utility of MMN as a neurobiological marker used to determine risk for alcohol misuse in BD.