The effect of alterations of schizophrenia-associated genes on gamma band oscillations

Christoph Metzner, Tuomo Mäki-Marttunen, Gili Karni, Hana McMahon-Cole, Volker Steuber

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Abstract

Abnormalities in the synchronized oscillatory activity of neurons in general and, specifically in the gamma band, might play a crucial role in the pathophysiology of schizophrenia. While these changes in oscillatory activity have traditionally been linked to alterations at the synaptic level, we demonstrate here, using computational modeling, that common genetic variants of ion channels can contribute strongly to this effect. Our model of primary auditory cortex highlights multiple schizophrenia-associated genetic variants that reduce gamma power in an auditory steady-state response task. Furthermore, we show that combinations of several of these schizophrenia-associated variants can produce similar effects as the more traditionally considered synaptic changes. Overall, our study provides a mechanistic link between schizophrenia-associated common genetic variants, as identified by genome-wide association studies, and one of the most robust neurophysiological endophenotypes of schizophrenia.
Original languageEnglish
Article number46
Number of pages10
JournalSchizophrenia
Volume8
Issue number1
Early online date28 Apr 2022
DOIs
Publication statusPublished - 28 Apr 2022

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