The Cognitive Neurophysiology Laboratory, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Transl Psychiatry. 2020 Mar 5;10(1):85. doi: 10.1038/s41398-020-0764-3.
22q11.2 Deletion Syndrome (22q11.2DS) is the strongest known molecular risk factor for schizophrenia. Brain responses to auditory stimuli have been studied extensively in schizophrenia and described as potential biomarkers of vulnerability to psychosis. We sought to understand whether these responses might aid in differentiating individuals with 22q11.2DS as a function of psychotic symptoms, and ultimately serve as signals of risk for schizophrenia. A duration oddball paradigm and high-density electrophysiology were used to test auditory processing in 26 individuals with 22q11.2DS (13-35 years old, 17 females) with varying degrees of psychotic symptomatology and in 26 age- and sex-matched neurotypical controls (NT). Presentation rate varied across three levels, to examine the effect of increasing demands on memory and the integrity of sensory adaptation. We tested whether N1 and mismatch negativity (MMN), typically reduced in schizophrenia, related to clinical/cognitive measures, and how they were affected by presentation rate. N1 adaptation effects interacted with psychotic symptomatology: Compared to an NT group, individuals with 22q11.2DS but no psychotic symptomatology presented larger adaptation effects, whereas those with psychotic symptomatology presented smaller effects. In contrast, individuals with 22q11.2DS showed increased effects of presentation rate on MMN amplitude, regardless of the presence of symptoms. While IQ and working memory were lower in the 22q11.2DS group, these measures did not correlate with the electrophysiological data. These findings suggest the presence of two distinct mechanisms: One intrinsic to 22q11.2DS resulting in increased N1 and MMN responses; another related to psychosis leading to a decreased N1 response.
22q11.2 缺失综合征（22q11.2DS）是目前已知的最强的精神分裂症分子风险因素。听觉刺激的大脑反应在精神分裂症中得到了广泛的研究，并被描述为精神病易感性的潜在生物标志物。我们试图了解这些反应是否可以帮助区分 22q11.2DS 个体，作为精神症状的功能，最终作为精神分裂症风险的信号。使用时长偶发范式和高密度电生理学来测试 26 名 22q11.2DS 个体（13-35 岁，17 名女性）的听觉处理能力，这些个体具有不同程度的精神病症状，以及 26 名年龄和性别匹配的神经典型对照（NT）。呈现率在三个水平上变化，以检查对记忆和感官适应完整性的要求增加的影响。我们测试了通常在精神分裂症中减少的 N1 和失匹配负波（MMN）是否与临床/认知测量相关，以及它们如何受到呈现率的影响。N1 适应效应与精神病症状相互作用：与 NT 组相比，没有精神病症状的 22q11.2DS 个体表现出更大的适应效应，而有精神病症状的个体表现出较小的效应。相比之下，无论是否存在症状，22q11.2DS 个体的 MMN 振幅都表现出呈现率增加的效应。虽然 22q11.2DS 组的智商和工作记忆较低，但这些测量与电生理数据没有相关性。这些发现表明存在两种不同的机制：一种是 22q11.2DS 固有的，导致 N1 和 MMN 反应增加；另一种与精神病有关，导致 N1 反应减少。
