Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: characterization of demographic, clinical, cognitive, and functional correlates in COGS-2.
Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: characterization of demographic, clinical, cognitive, and functional correlates in COGS-2.
复制标题
DOI：
10.1016/j.schres.2014.09.042
复制
发表时间：
2015-04
影响因子：
4.5
通讯作者：
Turetsky, Bruce I.
中科院分区：
文献类型：
--
作者：
Light, Gregory A.;Swerdlowa, Neal R.;Thomas, Michael L.;Calkins, Monica E.;Green, Michael F.;Greenwood, Tiffany A.;Gur, Raquel E.;Gur, Ruben C.;Lazzeroni, Laura C.;Nuechterlein, Keith H.;Pela, Marlena;Radant, Allen D.;Seidman, Larry J.;Sharp, Richard F.;Siever, Larry J.;Silverman, Jeremy M.;Sprock, Joyce;Stone, William S.;Sugar, Catherine A.;Tsuang, Debby W.;Tsuang, Ming T.;Braff, David L.;Turetsky, Bruce I.
错配负波（MMN）和P3a是听觉事件相关电位（ERP）的组成部分，在精神分裂症（SZ）患者中表现出强大的缺陷，并表现出内在表型的质量，包括大量的遗传性，重测信度和特质样稳定性。这些指标也符合在结果研究中用作认知和功能相关生物标志物的标准，但尚未被验证可用于大规模多中心临床研究。本研究测试了将MMN和P3a加入正在进行的精神分裂症遗传学联盟（COGS）研究的可行性。人口统计学、临床、认知和功能特征对MMN和P3a振幅变异性的影响程度也进行了研究。参与者（HCS n=824，SZ n=966）在5个地理分布的COGS实验室进行了测试。从91%的HCS和91%的SZ患者中获得了有效的ERP数据。在SZ患者中观察到高度显著的MMN（d=0.96）和P3a（d=0.93）振幅降低，幅度与单实验室研究中观察到的幅度相当，实验室间无明显差异。人口统计学特征分别占MMN和P3a振幅方差的26%和18%。SZ患者经人口统计学调整的MMN和P3a指标与药物治疗状态以及临床、认知和功能特征之间存在显著相关性。这项研究表明，MMN和P3a ERP生物标志物可以在多中心临床研究中使用。与许多脑功能的临床测试一样，人口统计学因素对MMN和P3a振幅有影响，在未来的生物标志物临床研究中应仔细考虑。
Mismatch negativity (MMN) and P3a are auditory event-related potential (ERP) components that show robust deficits in schizophrenia (SZ) patients and exhibit qualities of endophenotypes, including substantial heritability, test-retest reliability, and trait-like stability. These measures also fulfill criteria for use as cognition and function-linked biomarkers in outcome studies, but have not yet been validated for use in large-scale multi-site clinical studies. This study tested the feasibility of adding MMN and P3a to the ongoing Consortium on the Genetics of Schizophrenia (COGS) study. The extent to which demographic, clinical, cognitive, and functional characteristics contribute to variability in MMN and P3a amplitudes was also examined. Participants (HCS n=824, SZ n=966) underwent testing at 5 geographically distributed COGS laboratories. Valid ERP data was obtained from 91% of HCS and 91% of SZ patients. Highly significant MMN (d=0.96) and P3a (d=0.93) amplitude reductions were observed in SZ patients, comparable in magnitude to those observed in single-lab studies with no appreciable differences across laboratories. Demographic characteristics accounted for 26% and 18% of the variance in MMN and P3a amplitudes, respectively. Significant relationships were observed among demographically-adjusted MMN and P3a measures and medication status as well as several clinical, cognitive, and functional characteristics of the SZ patients. This study demonstrates that MMN and P3a ERP biomarkers can be feasibly used in multi-site clinical studies. As with many clinical tests of brain function, demographic factors contribute to MMN and P3a amplitudes and should be carefully considered in future biomarker-informed clinical studies.
登录
查看更多内容
影响因子：
2.6
作者：
Hall, Mei Hua;Schulze, Katja;Sham, Pak
通讯作者：
Sham, Pak
影响因子：
6.6
作者：
Calkins, Monica E.;Dobie, Dorcas J.;Braff, David L.
通讯作者：
Braff, David L.
影响因子：
2.9
作者：
Dulude, Louise;Labelle, Alain;Knott, Verner J.
通讯作者：
Knott, Verner J.
影响因子：
2.5
作者：
Jessen, F;Fries, T;Heun, R
通讯作者：
Heun, R
影响因子：
3.4
作者：
Braff, DL;Light, GA
通讯作者：
Light, GA