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

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.

Spectral signatures of cross-modal attentional control in the adolescent brain and their link with physical activity and aerobic fitness levels

“…Cognitive gamma oscillations (40-120 Hz) have been previously identified as supporting attention/inhibitory processing (Fries et al, 2001), and inhibitory GABAergic interneurons seem to be part of their key circuitry (Wang & Buzsáki, 1996). Indeed, auditory 40 Hz ASSRs/gamma oscillations have been associated with inhibitory control abnormalities in disorders such as autism (Seymour et al, 2020) and schizophrenia (Metzner et al, 2022). This also suggests that the auditory 40 Hz SSRs in the left temporal cortex in the present study, and its age effects in adolescents, could reflect the developmental stage of inhibitory processes in these cortical networks.…”

40-Hz Auditory Steady-State Responses in Schizophrenia: Toward a Mechanistic Biomarker for Circuit Dysfunctions and Early Detection and Diagnosis

“…There is preliminary evidence that unaffected first-degree relatives exhibit reductions in 40-Hz ASSRs (73). Moreover, computational modeling has shown the impact of common variants on 40-Hz ASSRs (74), suggesting that 40-Hz ASSR deficits are closely linked to genetic risk and therefore could constitute an endophenotype. This possibility is consistent with data showing that 40-Hz ASSR deficits can also be found in conditions that are characterized by overlapping circuit dysfunctions and genetics, such as bipolar disorder and autism spectrum disorder (75)(76)(77)(78).…”