Mismatch negativity in subjects at high risk for alcoholism

Alcohol Clin Exp Res. 2001 Mar;25(3):330-7. doi: 10.1097/00000374-200103000-00003.


Background: Evidence from P300 studies in both alcohol-dependent and high-risk (HR) individuals suggests that the reduced P300 amplitudes that often characterize these individuals may reflect a deficit in inhibition (hyperexcitability) in the central nervous system. In this context, the mismatch negativity (MMN) was investigated in the male and female HR offspring of alcohol-dependent fathers and a mixed-sex, low-risk (LR) control group.

Methods: As subjects read popular materials, they received a random sequence of 500 binaurally presented tones of 600 Hz and 1600 Hz. The designation of the rare stimulus (n = 60 trials) and frequent stimulus (n = 440 trials) was alternated across subjects. Recordings of MMN were made from 61 electrodes; risk group comparisons were restricted to the five frontal midline electrodes: Fpz, Afz, Fz, Fcz, and Cz. The MMN was obtained by calculating the integral of the area under the curve for both the frequent and rare waveforms over an interval from 100 to 190 msec and then subtracting the former from the latter.

Results: The primary observation was that MMN responses in the HR group were significantly larger than those in the LR group. In addition, both LR and HR individuals manifested differential responses to the rare and frequent stimuli, and MMN responses in both groups were largest at Fcz and smallest at Fpz.

Discussion: The results indicate that individuals at high risk for alcoholism differ electrophysiologically from LR controls. These differences were manifested as larger magnitudes of the MMN. The findings suggest the possibility that as measured by the MMN, individuals at high risk for alcoholism may be characterized by a deficit in inhibition (excessive neural excitation). The presence of these preexisting central nervous system states may lead to ethanol use for self-medication, which then may facilitate the development of both tolerance to and dependence on ethanol.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alcoholism / genetics
  • Alcoholism / physiopathology*
  • Analysis of Variance
  • Disease Susceptibility / physiopathology
  • Evoked Potentials, Auditory / physiology*
  • Female
  • Humans
  • Male
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Risk Factors
  • Serotonin / metabolism


  • Receptors, N-Methyl-D-Aspartate
  • Serotonin