Biological and Behavioral Markers of Persistent Speech Sound Disorders

描述（由申请人提供）：语音障碍（SSD）是儿童早期最常见的沟通障碍类型，通常会使个人面临日后学习困难的风险。SSD持续超过8岁的个体在长期社会情感、学业和职业方面表现不佳的风险最高。到目前为止，还没有大型的前瞻性研究来确定持续性SSD的遗传、激素和行为风险因素，因此可能会发现风险最大的儿童，并通过干预措施进行早期治疗，以防止后来的不良反应。目前的建议是一项为期25年的SSD遗传研究的延续（一项严重语音障碍家族性研究；NIDCD资助号DC000528），该研究已经确定了SSD和共病语言障碍（LI）和阅读障碍（RD）的风险基因。我们发现，与女性相比，男性中最严重形式的SSD患病率更高。在我们之前的工作中发现的基因调节了参与早期大脑发育的雌激素水平，这可能解释了基因表达的性别差异。在拟议的项目中，我们将探索SSD儿童的激素差异，作为潜在的生物标志物，以识别持续性SSD风险最大的儿童。持久性SSD的预测模型将从风险基因、激素生物标志物和五种行为内表型（言语运动控制缺陷、语音记忆缺陷、语音处理缺陷、快速命名缺陷和词汇缺陷）中建立。300名患有早期SSD的儿童将在4-6岁和8-10岁时接受所有因素的检查。研究结果将揭示早期SDD患者易患的长期问题的预测因素，识别风险因素，并确定早期干预的目标缺陷，以确保更有利的教育、职业和行为结果。

DESCRIPTION (provided by applicant): Speech sound disorders (SSD) are the most prevalent type of communication disorder in early childhood and often place an individual at risk for later academic difficulties. Individuals whose SSD persists past 8 years of age are at highest risk for poor long-term social-emotional, academic, and vocational outcomes. To date, there have been no large prospective studies to identify genetic, hormonal, and behavioral risk factors for persistent SSD so that children at greatest risk may be identified and treated early with interventions to prevent later adverse effects. The present proposal is a continuation of a 25 year genetic study of SSD (A Familial Study of Severe Phonology Disorders; NIDCD grant number DC000528) that has identified risk genes for SSD and co- morbid language impairment (LI) and reading disorders (RD). We found a higher prevalence of the most severe forms of SSD in males compared to females. Genes identified in our prior work regulate estrogen levels involved in early brain development, which may account for gender differences in gene expression. In the proposed project we will explore hormonal differences in children with SSD as a potential biomarker to identify children at greatest risk for persistent SSD. Predictive models for persistent SSD will be built from risk genes, hormonal biomarkers, and five behavioral endophenotypes: deficits in speech motor control, phonological memory, phonological processing, speeded naming, and vocabulary. Three hundred children with early SSD will be examined for all factors at 4-6 years of age and again at 8-10 years of age. Findings will reveal predictors of long-term problems to which individuals with early SDD are vulnerable, identify risk factors, and determine deficits to target in early interventions to insure more favorable educational, vocational, and behavioral outcomes.