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Autism-associated biomarkers: test–retest reliability and relationship to quantitative social trait variation in rhesus monkeys
Molecular Autism ( IF 6.3 ) Pub Date : 2021-07-08 , DOI: 10.1186/s13229-021-00442-w
Ozge Oztan 1 , Catherine F Talbot 2 , Emanuela Argilli 3 , Alyssa C Maness 2 , Sierra M Simmons 2 , Noreen Mohsin 1 , Laura A Del Rosso 2 , Joseph P Garner 1, 4 , Elliott H Sherr 3 , John P Capitanio 2, 5 , Karen J Parker 1, 2
Affiliation  

Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1–3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: “Case 2A” intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. All biological measures (except AKT) showed significant test–retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects). These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.

中文翻译:

自闭症相关生物标志物:重测信度和恒河猴数量社会特征变异的关系

恒河猴 (Macaca mulatta) 在社会特征方面表现出明显的个体差异,这是通过修订后的猕猴社会反应量表测量的。猕猴社会反应量表以前改编自社会反应量表,这是一种旨在评估人类社会和自闭症特征变异的工具。为了更好地了解这种行为变异的潜在生物学基础,我们评估了先前与自闭症有关的几种生物学测量(例如,精氨酸加压素、催产素及其受体,以及 ERK1/2、PTEN 和 AKT)的特征样一致性。 1-3)来自RAS-MAPK和PI3K-AKT途径)。我们还测试了哪些生物学指标可以预测猕猴社会反应量表的修订分数。从 N = 76 只雄性猴子身上采集脑脊液和血液样本,其中,作为样本,在猕猴社会反应量表修订版上显示出连续分布。在这些受试者的一个子集中(n = 43),样本在 10 个月内收集了三次。使用了以下统计测试:“案例 2A”一致性的类内相关系数、主成分分析和一般线性建模。所有生物学测量(AKT 除外)在不同时间点的个体内均显示出显着的重测信度。接下来,我们对第一个时间点(n = 57)具有完整生物测量集的猴子的数据进行了主成分分析,以探索可靠的生物学测量与其与猕猴社会反应量表修订评分之间的潜在相关性;找到了一种三组分溶液。后续分析显示,脑脊液精氨酸加压素浓度,但没有其他生物学测量,有力地预测了猕猴社会反应量表修订分数的个体差异,因此脑脊液精氨酸加压素浓度最低的猴子表现出最大的社会损害。最后,我们证实这一结果在更大的研究样本中成立(其中脑脊液精氨酸加压素值可从 n = 75 名受试者中获得)。这些发现表明,脑脊液精氨酸加压素浓度是一种稳定的性状样测量,它与雄性恒河猴的数量社会性状变异有关。有力地预测了猕猴社会反应量表修订分数的个体差异,因此脑脊液精氨酸加压素浓度最低的猴子表现出最大的社会障碍。最后,我们证实这一结果在更大的研究样本中成立(其中脑脊液精氨酸加压素值可从 n = 75 名受试者中获得)。这些发现表明,脑脊液精氨酸加压素浓度是一种稳定的性状样测量,它与雄性恒河猴的数量社会性状变异有关。有力地预测了猕猴社会反应量表修订分数的个体差异,因此脑脊液精氨酸加压素浓度最低的猴子表现出最大的社会障碍。最后,我们证实这一结果在更大的研究样本中成立(其中脑脊液精氨酸加压素值可从 n = 75 名受试者中获得)。这些发现表明,脑脊液精氨酸加压素浓度是一种稳定的性状样测量,它与雄性恒河猴的数量社会性状变异有关。我们证实这一结果在更大的研究样本中成立(其中脑脊液精氨酸加压素值可从 n = 75 名受试者中获得)。这些发现表明,脑脊液精氨酸加压素浓度是一种稳定的性状样测量,它与雄性恒河猴的数量社会性状变异有关。我们证实这一结果在更大的研究样本中成立(其中脑脊液精氨酸加压素值可从 n = 75 名受试者中获得)。这些发现表明,脑脊液精氨酸加压素浓度是一种稳定的性状样测量,它与雄性恒河猴的数量社会性状变异有关。
更新日期:2021-07-08
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