Serotonergic dysfunction in schizophrenia assessed by the loudness dependence measure of primary auditory cortex evoked activity.

Increased serotonergic activity is discussed as an important pathogenetic factor in schizophrenia. Further support for this hypothesis is difficult to obtain due to the lack of valid indicators of the brain's serotonin system. A great deal of evidence discovered through human and animal studies suggests that a weak loudness dependence of auditory evoked potentials (LDAEP) indicates high serotonergic activity and vice versa. The LDAEP is a measure of auditory cortex activity, reflecting increase or decrease of auditory evoked potential amplitudes with increasing tone loudness, which is probably modulated by the serotonergic innervation there. This is true only for the LDAEP of the primary auditory cortex, since this region is more highly innervated by serotonergic fibers than the secondary auditory cortex. The LDAEP (N1/P2 component) of 25 inpatients with schizophrenia free of medication and 25 healthy controls matched by age and gender, were recorded. Using dipole source analysis, the LDAEP of primary (tangential dipole) and this of secondary auditory cortex (radial dipole) was separately analyzed. Following a 4-week treatment with the 5-HT(2) antagonists clozapine or olanzapine, patients were once again studied. The LDAEP of the primary, but not of the secondary auditory cortex, was significantly weaker in the patients with schizophrenia than in healthy volunteers, indicating enhanced serotonergic neurotransmission. After treatment with the 5-HT(2) antagonists, the LDAEP (of the right hemisphere) tended to be increased, indicating normalization of serotonergic function in the patients with schizophrenia. These results suggest that the loudness dependence of primary auditory cortex evoked activity is well suitable to assess serotonergic dysfunction in schizophrenia.