Pentz Atle Bråthen, O'Connel Kevin Sean, van Jole Oda, Timpe Clara Maria Fides, Slapø Nora Berz, Melle Ingrid, Lagerberg Trine Vik, Steen Nils Eiel, Westlye Lars T, Haukvik Unn K, Moberget Torgeir, Jönsson Erik G, Andreassen Ole A, Elvsåshagen Torbjørn
NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway.
NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway.
Schizophr Res. 2024 Feb;264:314-326. doi: 10.1016/j.schres.2024.01.013. Epub 2024 Jan 11.
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).
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.
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.
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.
听觉失配负波（MMN）损伤是精神障碍的一种候选内表型，但其遗传基础仍有待阐明。在此，我们研究了精神障碍患者（包括精神分裂症谱系障碍（SSD）和双相情感障碍（BD））以及健康对照者（HC）的听觉MMN与多基因风险评分（PRS）之间的关系。
对患有精神障碍（n = 102，包括SSD（n = 43）和BD（n = 59））以及HC（n = 397）的基因分型且临床特征明确的个体进行了移动MMN范式测试。除MMN外，我们还测量了重复正波（RP）和偏差负波（DN）的记忆痕迹，据信它们分别反映预测编码和预测误差信号。使用最新全基因组关联研究的汇总统计数据计算SCZ和BD的PRS。通过线性回归评估MMN、RP和DN与PRS之间的关系。
我们发现，在精神障碍组或HC组中，SCZ或BD的PRS与总体平均MMN之间无显著关联（所有p > 0.05）。在精神障碍组中，SCZ PRS和BD PRS与RP呈负相关（β = -0.46，t = -2.86，p = 0.005；β = -0.29，t = -0.21，p = 0.034）。未发现DN与PRS之间存在显著关联。
这些发现表明，与SCZ和BD相关的基因变异可能与精神障碍患者中与预测编码相关的MMN子成分有关。需要更大规模的研究来证实这些发现，并进一步阐明精神障碍中MMN损伤的遗传基础。
