Earls Holly A, Curran Tim, Mittal Vijay
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO.
Department of Psychology, Northwestern University, Evanston, IL.
Schizophr Bull. 2016 Nov;42(6):1504-1516. doi: 10.1093/schbul/sbw047. Epub 2016 May 23.
As endophenotypes bridge the gap between genetics and phenotypic disease expression, identifying reliable markers is important for fostering understanding of pathophysiology. The present aim was to conduct current meta-analyses of 3 key auditory event-related potential (ERP) components that have been held as potential endophenotypes for schizophrenia: P50, P300 amplitude and latency, and mismatch negativity (MMN), reflective of sensory gating, attention and classification speed, and perceptual discrimination ability, respectively. In order to assess endophenotype viability, these components were examined in unaffected relatives of patients with schizophrenia and healthy controls.
Effect sizes (ES) were examined between relatives and controls for P50 suppression (10 studies, n = 360 relatives, 473 controls), P300 amplitude (20 studies, n = 868 relatives, 961 controls), P300 latency (17 studies, n = 674 relatives, 792 controls), and MMN (11 studies, n = 377 relatives, 552 controls).
Reliable differences in P50 suppression (ES = 0.86, P < .001), P300 amplitude (ES = -0.52, P < .001), and P300 latency (ES = 0.44, P < .05) were found between unaffected relatives and controls. A trend was found between relatives and controls for MMN (ES = 0.21, P = 0.06), and the use of extraneous channels was found to be a significant moderator (P = 0.01). When MMN was analyzed using frontocentral channel Fz, a significant difference was found (ES = 0.26, P < 0.01).
The results indicate that P50 suppression, P300 amplitude and P300 latency, and MMN may serve as viable endophenotypes for schizophrenia.
由于内表型在遗传学和疾病表型表达之间架起了桥梁，识别可靠的标志物对于促进对病理生理学的理解非常重要。当前的目标是对3种关键的听觉事件相关电位（ERP）成分进行荟萃分析，这3种成分一直被视为精神分裂症的潜在内表型：P50、P300波幅和潜伏期，以及失匹配负波（MMN），它们分别反映了感觉门控、注意力和分类速度，以及感知辨别能力。为了评估内表型的可行性，在精神分裂症患者的未患病亲属和健康对照中对这些成分进行了检测。
对P50抑制（10项研究，n = 360名亲属，473名对照）、P300波幅（20项研究，n = 868名亲属，961名对照）、P300潜伏期（17项研究，n = 674名亲属，792名对照）和MMN（11项研究，n = 377名亲属，552名对照）的亲属与对照之间的效应大小（ES）进行了检测。
在未患病亲属与对照之间，发现P50抑制（ES = 0.86，P <.001）、P300波幅（ES = -0.52，P <.001）和P300潜伏期（ES = 0.44，P <.05）存在可靠差异。在亲属与对照之间发现MMN有一个趋势（ES = 0.21，P = 0.06），并且发现使用无关通道是一个显著的调节因素（P = 0.01）。当使用额中央通道Fz分析MMN时，发现了显著差异（ES = 0.26，P < 0.01）。
结果表明，P50抑制、P300波幅和P300潜伏期以及MMN可能是精神分裂症可行的内表型。
