Childhood anxiety is one of the most prevalent, common, and costly psychiatric disorders, with economic costs in the US estimated at over 40 billion USD per year. [15] As such, there is a critical need for earlier, more accurate diagnoses of pediatric anxiety disorders. Research has implicated threat bias, defined as preferential attention to threat, in the etiology of anxiety disorders. [1] However, it is unclear whether clinically-significant anxiety in young children is signaled by early (i.e., increased orienting to threat) or late (i.e., difficulty disengaging from threat) components of threat bias, or both. Determining the extent to which early or late threat bias components serve as reliable neurobehavioral markers of anxiety disorders in the early school- aged years -- a developmental period when rates of anxiety disorders begin to rise -- could reduce the public health and private burden of this illness. Specifically, this information could: (a) improve assessment protocols for differentiating between normative vs. clinical levels of anxiety, (b) elucidate altered attention control as a risk mechanism that could be directly targeted in treatment, (c) identify disruptions in a RDoC construct, "response to threat" systems, that are relevant for understanding the pathophysiology of anxiety disorders, and (d) determine underlying causes of maladaptive real-world responses to threat, which would in turn, (e) improve clinical efforts aimed at preventing the negative squeal of childhood-onset anxiety disorders. Thus, the candidate's immediate focus is to investigate altered attention control as a potential neurobehavioral marker of clinically-significant anxiety in young school-aged children. Using an affective variant of a spatil cueing paradigm (Posner task), behavioral and electro cortical indices of threat bias will be assessed in a sample of anxious (N = 60) and non-anxious (N = 30) young children, aged 6-9 years. Children with specific phobia, social phobia, and separation anxiety disorders will be recruited for the anxious sample and enrollment will be monitored to ensure that at least 30 anxious children meet criteria for a moderate-to- severe impairment.
Aim 1 will determine the extent to which the late component of threat bias differentiates between children with and without anxiety. To further determine the clinical significance of early and late threat bias indics for pediatric anxiety disorders, Aim 2.1 will examine relations between magnitude of early vs. late threat bias components and severity of parent-rated symptoms. Using experience sampling method (ESM) and a device called the Electronically-Activated Recorder (EAR), Aim 2.2 will determine the real-world significance of alterations in anxious children's attention responses to threat by modeling relations between indices of early and late threat bias and real-world indices of altered ER, specifically level of negative affect, sustained focus on negative events (worry, rumination), and ability to use regulatory strategies that require attention control (cognitive restructuring, distraction). To appropriately test these Aims and to develop as an independent neurobehavioral scientist, the candidate seeks to build on her strong foundation in developmental psychopathology and early childhood emotion regulation (ER) with advanced training in: 1) developmental cognitive affective neuroscience approaches for understanding typical and atypical ER, particularly in relation to developing affective circuitry and the pathophysiology of anxiety, 2) designing, adapting, and implementing EEG/ERP methods to assess threat processing in young children, with an emphasis on paradigms and analytic methods that leverage the temporal sensitivity of EEG for identifying anxiety-related disruptions in cognitive control processes that unfold as children process and respond to emotional information, 3) ecologically-sensitive methods for assessing real- world ER behaviors in young clinical populations, and 4) statistical tools for integrating brain-behavior time series data and or modeling the temporal features of ER processes. The University Of Pittsburgh School Of Medicine is an outstanding environment in which to engage in the interdisciplinary training required to achieve these goals. The candidate's mentorship team has extensive experience in developmental cognitive affective neuroscience (Drs. Siegle, Ladouceur, Pine, and Silk), innovation of novel ecologically-sensitive methods for assessing clinically-relevant child behaviors (Drs. Silk and Slatcher), utilization of EEG/ERP methods to investigate cognitive control processes in pediatric clinical populations (Drs. Ladouceur and Fox), assessment and diagnosis of pediatric anxiety disorders (Dr. Sakolsky), and advanced statistical tools for time series data (Drs. Lanza and Siegle). The proposed study is a first step in establishing the extent to which early vs. late threat bias components signifies clinically-significant anxiety in younger children. Findings will inform the design of larger R01 studies examining altered attention control as 1) a possible neurocognitive risk mechanism for differentiating risk among emotional disorders and anxiety subtypes, 2) a mediator of anxiety-related developmental trajectories, or 3) a target for change in the early intervention and prevention of pediatric anxiety disorders. In sum, the proposed K01 application would position the candidate for an innovative research career that integrates developmental, cognitive and affective neuroscience approaches to uncover the associations between brain and real-world behavior that underpin anxiety-related trajectories.

Public Health Relevance

Rates of anxiety rise sharply during the early elementary school years, setting the stage for the later development of chronic or recurrent anxiety disorders, depression, substance abuse, and social impairments. There is therefore a critical need for reliable, biologically-based markers of anxiety disorders in young school- aged children. The goals of the proposed training and research plan are designed to 1) examine the extent to which early vs. late threat bias components differentiate children with and without anxiety disorders and 2) reveal how threat bias is associated with symptom severity and real-world emotional functioning in anxious children. This approach could potentially elucidate neurobehavioral markers of pediatric anxiety disorders that can improve early detection and intervention, in turn altering well-being and disability into adulthood.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Psychosocial Development, Risk and Prevention Study Section (PDRP)
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Sarampote, Christopher S
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University of Pittsburgh
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