Generating an Earlier Science of When to Worry: A Neurodevelopmental, Transactional Approach to Characterizing Irritability Patterns Beginning in Infancy

 描述（由申请人提供）：易怒出现在婴儿期，是许多常见形式的发育性精神病理学的基础。然而，由于高水平的正常变异以及随着时间的推移，易激惹婴儿适应或适应不良结局的个体差异很大，因此可靠地识别易激惹婴儿的临床进展高风险具有挑战性。基于我们之前在学龄前的工作，拟议的研究利用神经发育框架来生成经验推导的参数，用于区分标记临床进展风险的易激惹模式。主要创新包括：（1）从婴儿期开始的发育非典型易怒模式的新方法;（2）对易怒、执行功能和前额叶皮层区域的联合发育考虑;（3）在父母-婴儿相互调节的背景下，检查早期易怒的临床意义的事务焦点。为了获得基于人群的参数，我们首先对12-36个月的代表性样本进行横断面调查。奥尔兹（N= 2，000）。然后，我们确定了一个独立的社区队列（N=350名因易怒而过度采样的婴儿），并进行了12-36个月的密集纵向随访。局灶性易激惹评估是：（a）通过语言环境分析（LENA）Pro设备每两个月一次的家长报告和易激发声的实时监测;和（B）每年直接观察易激惹的气质和行为（12、24和36个月）。执行功能的绩效评估每年进行一次。通过父母对LENA Pro（每两个月一次）和事件编码的父母-婴儿相互调节过程（每年一次）上婴儿易激性发声的偶然反应来评估transmittance过程。通过随时间推移的潜在维度临床风险捕获临床进展。具体目标：IA。通过基于人群的参数横截面（IAi）和定量纵向参数（IAii）区分发育非典型易怒模式从婴儿早期学龄前。IB.指定易激惹的纵向参数，以优化临床进展的预测。IIA-B将发育中的非典型易怒模式映射到执行功能和前额叶皮层（PFC）区域成熟的中断，并检验其联合考虑将增强预测临床效用的假设。在极端组子样本（n=100）中，将从12和36个月时的婴儿自然睡眠-MRI衍生的解剖学性质的估计来评估前额叶皮质成熟。我们测试的假设，非典型的易怒模式将预测执行功能发育迟缓和异常PFC解剖。IIIA-B.阐明交易过程如何塑造临床预测，检验父母-婴儿相互调节过程调节临床进展的假设。在交易背景下的神经发育易激惹表型的规范提供了一个关键的经验基础，有针对性地预防精神障碍在其最早的前驱阶段。

 DESCRIPTION (provided by applicant): Irritability emerges during infancy and is a substrate of many common forms of developmental psychopathology. However, reliable identification of irritable infants at high risk for clinical progression is challenging due to high levels of normatve variation combined with substantial individual differences in adaptive or maladaptive outcomes for irritable infants over time. Building on our prior work at preschool age, the proposed study utilizes a neurodevelopmental framework to generate empirically derived, parameters for differentiation of irritability patterns that mark risk for clinical progression. Key innovations ae: (1) novel approach to specification of developmentally atypical patterns of irritability beginning n infancy; (2) joint developmental consideration of irritability, executive function, and prefrontal cortical regions; and (3) transactional focus examining the clinical import of early irritability wthin the context of parent-infant mutual (dys)regulation. To derive population-based parameters, we first conduct a cross-sectional survey of a representative sample of 12-36 mos. olds (N=2,000). We then ascertain an independent community cohort (N=350 infants oversampled for irritability), with intensive longitudinal follow-up from 12-36 months. Focal irritability assessments are: (a) bimonthly parent reports and real-time monitoring of irritable vocalizations via the Language Environment Analysis (LENA) Pro device; and (b) annual direct observations of irritable temperament and behavior (12, 24 & 36 mos.). Performance-based assessments of executive function occur annually. Transactional processes are assessed via parental contingent responses to infant irritable vocalizations on the LENA Pro (bimonthly) and event-coded parent-infant mutual regulation processes (annually). Clinical progression is captured via latent dimensional clinical risk over time. SPECIFIC AIMS: IA. Differentiate developmentally atypical irritability patterns from infancy-early preschool age via population-based parameters cross-sectionally (IAi) and quantitative longitudinal parameters (IAii). IB. Specify longitudinal parameters of irritability to optimize prediction of clinical progression. IIA-B. Map developmentally atypical irritability patterns to disruptions in the maturation of executive functin and prefrontal cortical (PFC) regions and test the hypothesis that their joint consideration will enhance predictive clinical utility. Prefrontal cortical maturation will be assessed from infant natural sleep-MRI derived estimates of anatomical properties at 12 & 36 months in an extreme group sub-sample (n=100). We test the hypothesis that atypical irritability patterns will predict slowed executive function development and abnormal PFC anatomy. IIIA-B. Elucidate how transactional processes shape clinical prediction, testing the hypothesis that parent-infant mutual regulation processes modulate clinical progression. Specification of neurodevelopmental irritability phenotypes within transactional context provides a critical empirical base for targete prevention of mental disorder in its earliest prodromal phases.