Mismatch negativity and polygenic risk scores for schizophrenia and bipolar disorder.

Abstract

OBJECTIVE:

Auditory mismatch negativity (MMN) impairment is a candidate endophenotype in psychotic disorders, yet the genetic underpinnings remain to be clarified. Here, we examined the relationships between auditory MMN and polygenic risk scores (PRS) for individuals with psychotic disorders, including schizophrenia spectrum disorders (SSD) and bipolar disorder (BD) and in healthy controls (HC).

METHODS:

Genotyped and clinically well-characterized individuals with psychotic disorders (n = 102), including SSD (n = 43) and BD (n = 59), and HC (n = 397) underwent a roving MMN paradigm. In addition MMN, we measured the memory traces of the repetition positivity (RP) and the deviant negativity (DN), which is believed to reflect prediction encoding and prediction error signals, respectively. SCZ and BD PRS were computed using summary statistics from the latest genome-wide association studies. The relationships between the MMN, RP, and DN and the PRSs were assessed with linear regressions.

RESULTS:

We found no significant association between the SCZ or BD PRS and grand average MMN in the psychotic disorders group or in the HCs group (all p > 0.05). SCZ PRS and BD PRS were negatively associated with RP in the psychotic disorders group (β = -0.46, t = -2.86, p = 0.005 and β = -0.29, t = -0.21, p = 0.034, respectively). No significant associations were found between DN and PRS.

CONCLUSION:

These findings suggest that genetic variants associated with SCZ and BD may be associated with MMN subcomponents linked to predictive coding among patients with psychotic disorders. Larger studies are needed to confirm these findings and further elucidate the genetic underpinnings of MMN impairment in psychotic disorders.

• Authors: Atle Bråthen Pentz, Kevin Sean O'Connel, Oda van Jole, Clara Maria Fides Timpe, Nora Berz Slapø, Ingrid Melle, Trine Vik Lagerberg, Nils Eiel Steen, Lars T Westlye, Unn K Haukvik, Torgeir Moberget, Erik G Jönsson, Ole A Andreassen, Torbjørn Elvsåshagen
• Journal: Schizophrenia research (Schizophr Res) Vol. 264 Pg. 314-326 (Feb 2024) ISSN: 1573-2509 [Electronic] Netherlands
• PMID: 38215567 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Topics

• Humans
• Bipolar Disorder (genetics)
• Schizophrenia (genetics)
• Genetic Risk Score
• Genome-Wide Association Study
• Psychotic Disorders (genetics)