Dimensions of Early Temper Loss and Low Concern: Clinical Utility and Mechanisms

精神障碍起源于神经发育，通常出现在生命早期。然而，缺乏方法 用于区分处于慢性临床路径开始阶段的临床弱势幼儿和 他们的问题是暂时的。对发展敏感的维度措施的出现， 脑功能的测量为提高预防目标的准确性提供了有力的机会。一体化 这些方面与发展为基础的神经科学方法产生了一个新的，真正的 “神经发育”的角度来推进NIMH战略计划目标1.4，“发展，研究 目的，根据可观察行为的维度对精神障碍进行分类的新方法， 神经生物学测量。“破坏性行为是应用这种方法的理想场所，因为它出现得很早， 并且是高达60%的成人精神障碍的先兆。此外，破坏性材料的具体组件尺寸 行为，即，易激惹和冷酷/冷漠特征，预测不同的临床过程和神经系统疾病的模式， 旧的临床样本的破坏。我们的MAPS研究的最新发现为这些模式提供了支持， 学龄前儿童这种竞争性更新的总体目标是确定发育敏感的标志物， 在病理生理学途径的早期阶段的非典型易怒和胼胝特征，并证明 这些标记物区分慢性精神障碍风险最高的幼儿的能力。我们提出了一个 MAPS研究（1 R 01 MH 082830）的纵向随访，这是一项包含400名学龄前儿童（3-5岁）的多样化队列研究。我们 利用MAPS的发展敏感的易怒（“脾气损失”），无情的维度评估 特质（“低关心他人”），以及相关的神经认知标志物。这项研究将这些早期的 儿童数据至学龄早期（6-8岁）和青春期前（9-10岁）结果。具体目标：（一） 详细说明预测慢性临床疾病的早期儿童脾气失控和低关注度的维度属性 模式;（二）指定维度属性的早期儿童脾气损失和低关注，预测前 青少年神经认知障碍，包括神经成像子样本中基于任务的fMRI大脑活动 （n=120）;（III）测试联合考虑儿童早期脾气丧失和低关注的增量效用 维度属性和神经认知标记，以增强连续性和不连续性的预测。 利用大脑中有关早期生命活动的信息：行为关系预测精神障碍的病程 将推进预测心理健康结果的目标。研究结果将为有针对性的 旨在早期改变精神障碍的生命轨迹的预防。

Mental disorders are neurodevelopmental in origin and often emerge in early life. However, methods are lacking for distinguishing clinically vulnerable young children who are at the start of a chronic clinical pathway from those whose problems are transient. The advent of developmentally-sensitive dimensional measures designed to link to measures of brain function provides a potent opportunity to enhance accuracy of prevention targets. Integration of these dimensions with developmentally-based neuroscientific methods generates a novel, truly "neurodevelopmental"perspective with which to advance NIMH Strategic Plan Goal 1.4, "to develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures."Disruptive behavior is an ideal venue for applying this approach as it emerges early, and is antecedent to up to 60% of adult mental disorders. Further, specific component dimensions of disruptive behavior, i.e., irritability and callous/unemotional traits, predict differential clinical courses and patterns of neural disruption in older clinical samples. Recent findings from our MAPS Study provide support for these patterns in preschoolers. The overarching goal of this competitive renewal is to identify developmentally-sensitive markers of atypical irritability and callous traits at an early phase of the pathophysiological pathway, and to demonstrate the ability of these markers to distinguish young children at highest risk for chronic mental disorder. We propose a longitudinal follow-up of the MAPS Study (1R01MH082830), a diverse cohort of 400 preschoolers (3-5 yrs.). We capitalize on MAPS' developmentally-sensitive dimensional assessment of irritability ("Temper Loss"), callous traits ("Low Concern for Others"), and associated neurocognitive markers. The proposed study links these early childhood data to early school age (6-8 yrs.) and pre-adolescent (9-10 yrs.) outcomes. SPECIFIC AIMS: (I) Specify dimensional attributes of early childhood Temper Loss and Low Concern that predict chronic clinical patterns; (II) Specify dimensional attributes of early childhood Temper Loss and Low Concern that predict pre- adolescent neurocognitive disruptions, including task-based fMRI brain activity in a neuroimaging subsample (n=120); (III) Test the incremental utility of jointly considering early childhood Temper Loss and Low Concern dimensional attributes and neurocognitive markers to enhance prediction of continuities and discontinuities. Utilizing information about early life atypicalities in brain:behavior relations to predict course of mental disorder will advance the goal of predicting mental health outcomes. Study findings will lay the groundwork for targeted prevention designed to alter lifespan trajectories of mental disorder at early stages.