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Introduction The mismatch negativity (MMN) represents one of the major paradigms in cognitive neurophysiology. The attenuation of this subtraction wave of auditory event-related potentials (being a marker of discrimination of rare deviant stimuli among a series of standard stimuli) is well established in schizophrenia research. Moreover, first MMN results in patients with alcohol dependence mostly indicated an enhanced MMN though heterogeneously. In contrast to this “traditional” oddball MMN an optimized MMN including a higher number of deviants but within the same time interval was deficient in schizophrenia patients as shown by our group. Interestingly, the two clinical entities (schizophrenia, alcohol dependence) are in a close connection to glutamate neurotransmitter system underlying the generation of MMN. Methods 25 inpatients with alcohol dependence received a multichannel EEG with auditory MMN in i) oddball (20% deviants) as well as optimized MMN (50% standards, five deviants with 10% each). 25 healthy subjects without harmful use of alcohol served as controls. Results Following alcohol withdrawal patients showed decreased MMN amplitudes in the fronto-central region and increased latencies as compared to controls. Especially when taking the optimized MMN, the amplitudes of the cortico-central region significantly correlated positively (deviants: duration, intensity, localization: 0.001 > p ’s) with length of time of alcohol abstinence. Conclusion Attenuation of optimized MMN might indicate down-regulation of glutamatergic systems after withdrawal. Further, this study confirms the alteration of latencies representing delay of early auditory information processing in alcohol patients. Efficient neurospychobiological monitoring could improve diagnostic evaluation and potentially prediction of effects of psychotropic agents in patients with substance dependence. [ABSTRACT FROM AUTHOR]