TY - JOUR
T1 - The effect of alterations of schizophrenia-associated genes on gamma band oscillations
AU - Metzner, Christoph
AU - Mäki-Marttunen, Tuomo
AU - Karni, Gili
AU - McMahon-Cole, Hana
AU - Steuber, Volker
N1 - © The Author(s) 2022. This article is licensed under a Creative Commons
Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
PY - 2022/4/28
Y1 - 2022/4/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85128909585&partnerID=8YFLogxK
U2 - 10.1038/s41537-022-00255-7
DO - 10.1038/s41537-022-00255-7
M3 - Article
SN - 2334-265X
VL - 8
JO - Schizophrenia
JF - Schizophrenia
IS - 1
M1 - 46
ER -