Alterations of the early auditory evoked gamma-band response in first-degree relatives of patients with schizophrenia: Hints to a new intermediate phenotype

Background: There is growing evidence of abnormalities of high-frequency oscillations in the gamma-range of the electroencephalography in schizophrenia. The generation of neural activity in the gamma-band was shown to be critically related to a glutamatergic and GABAergic microcircuit which is also known to be involved in the pathophysiology of schizophrenia. Recently, a reduction of the early auditory evoked gamma-band response (eGBR) in schizophrenic patients was reported. In order to investigate the possible applicability of this neurophysiological marker as an intermediate phenotype for schizophrenia, this is the main question of our investigation: Is the early eGBR decreased regarding evoked power and phase locking in first-degree relatives of patients with schizophrenia? Methods: We investigated the early eGBR in 17 unaffected first-degree relatives of patients with schizophrenia and in age-, gender- and education-matched groups of schizophrenic patients and healthy controls using an auditory reaction task. Results: First-degree relatives of patients with schizophrenia and schizophrenic patients showed a significant reduction of evoked power and phase locking of the early eGBR compared to healthy controls. Conclusion: This study shows significantly reduced evoked power and phase locking of the early auditory eGBR in first-degree relatives of patients with schizophrenia pointing to the applicability of this marker as a heritable intermediate phenotype for schizophrenia. The findings are in line with the hypothesis of a disturbed GABAergic interneural modulation of pyramidal cells in schizophrenia and findings of different schizophrenia risk genes associated with transmission at glutamatergic and GABAergic synapses. (C) 2010 Elsevier Ltd. All rights reserved.