DESCRIPTION (provided by applicant): 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 t 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.

PUBLIC HEALTH RELEVANCE: Common mental disorders often begin early in life, but many clinically vulnerable young children do not develop mental disorders. The goal of this project is to utilize a novel neurodevelopmental, dimensional approach to identify early childhood profiles that reliably differentiate young children at highest risk for chronic mental disorder and associated neural disruptions from those with transient developmental problems. By utilizing information about early life atypicalities in brain: behavior relations to predict onset and course of clinical patterns, the study will advance the goal of generating a developmentally-based, neuroscientifically informed framework for enhancing longitudinal clinical outcome prediction. Findings from the study will lay the groundwork for targeted prevention designed to alter lifespan mental disorders via pinpointing intervention in the early phase of the clinical pathway to those children most at risk.