Impaired Mismatch Negativity Generation in Prodromal Subjects and Patients with Schizophrenia

Background: Mismatch negativity (MMN) specifically the response to tone duration deviants has consistently been shown to be reduced in schizophrenia suggesting dysfunction in auditory sensory memory. As part of a multidimensional approach to the early recognition of psychosis, MMN was investigated as a possible risk factor for later development of psychosis in subjects with a prodromal syndrome. Forty-three prodromal subjects, 31 neuroleptic-free inpatients with schizophrenia and 33 healthy controls were studied. A prodromal state was defined by a cluster 'Cognitive Disturbances' as defined by the 'Bonn Scale for the Assessment of Basic Symptoms' (BSABS), which was found highly predictive of first-episode schizophrenia. To elicit MMN, a three-tone auditory oddball paradigm with 10% 'duration deviants' and 10% 'frequency deviants' was used.

Results: MMN amplitudes to tone duration deviants were significantly reduced in the patients with schizophrenia compared to controls. The putatively prodromal subjects also showed a slight, though non-significant reduction of the MMN amplitude that was intermediate between normal controls and patients with schizophrenia, and with a larger within-group variance.

Conclusion: These results support the view that abnormalities in temporal processing are particularly pronounced in patients with schizophrenia. Prodromal subjects are a heterogeneous group with regard to outcome and time until transition to a first psychotic episode. Follow-up of these putatively prodromal subjects will show whether MMN amplitudes further reduce over time in those developing psychosis and if a reduction is state-dependent.