Dylan Gee - US grants

Currently, 50% of children do not benefit from evidence-based treatments for childhood anxiety disorders. This R61/R33 application proposes to test whether a novel entirely parent-based psychosocial intervention for childhood anxiety disorders engages amygdala-medial prefrontal cortex (mPFC) neural circuitry in the child's brain, implicated in children's reliance on parents to reduce their amygdala reactivity and anxiety; and whether changes in the target circuitry after treatment are associated with reductions in child anxiety. The R61 study will randomly assign 90 children (ages 7-10yrs) with primary anxiety disorders to one of two interventions: 1) Supportive Parenting for Anxious Childhood Emotions (SPACE), a novel completely parent- based treatment with no direct child involvement, that reduces children's anxiety by reducing parents' accommodation of their child's symptoms; or 2) Parent Educational Support (PES), a credible comparator intervention that is also entirely parent-based and controls for treatment duration and parent-therapist contact, but does not include any active modification of parental behavior. Before and after treatment, functional magnetic resonance imaging (fMRI) will be used examine children's reliance on parents to engage the target circuitry by comparing children's amygdala reactivity and mPFC connectivity in the presence of their mother and in the absence of their mother. We expect SPACE to reduce child reliance on parental presence to reduce amygdala reactivity, significantly more than PES. If this hypothesis is supported the R33 will be performed. The R33 will randomly assign 136 children (7-10yrs) with primary anxiety disorders to one of two interventions: 1) Parents participate in SPACE; or 2) Children receive cognitive-behavioral therapy (CBT), a standard of care treatment of known efficacy. We will use before and after fMRI and multi-informant/multi-modal child anxiety evaluations. We expect SPACE to reduce child reliance on parental presence to reduce amygdala reactivity, significantly more than CBT; We expect target engagement in SPACE to be associated with child anxiety symptom reduction; We expect SPACE will be feasible to deliver and acceptable to children and parents. This study is innovative in several ways and has the potential for large clinical and scientific impact. It is the first study to examine the impact of a psychosocial intervention on the neural circuitry of children with anxiety disorders, and the first study to examine the effects of an exclusively parent-only intervention with no child-therapist contact, on child brain circuitry. It will provide insight into the neurobiology of children's dependence on attachment figures for anxiety reduction, a process that contributes to the impairment and costs associated with childhood anxiety disorders. As many children are unable or unwilling to participate in therapy, results supporting the promise of SPACE as an effective way to reduce childhood anxiety would help to address a common barrier to treatment. Promising results from this study would provide the basis for a larger scale R01 clinical trial, to investigate the efficacy of SPACE and mediators and moderators of its effects.

Abstract Adolescent Brain Cognitive Development (ABCD) is the largest long-term study of brain development and child health in the United States. The ABCD Research Consortium consists of 21 research sites across the country, a Coordinating Center, and a Data Analysis and Informatics Resource Center. In its first five years, under RFA-DA-15-015, ABCD enrolled a diverse sample of 11,878 9-10 year olds from across the consortium, and will track their biological and behavioral development through adolescence into young adulthood. All participants received a comprehensive baseline assessment, including state-of-the-art brain imaging, neuropsychological testing, bioassays, careful assessment of substance use, mental health, physical health, and culture and environment. A similar detailed assessment recurs every 2 years. Interim in-person annual interviews and mid-year telephone or mobile app assessments provide refined temporal resolution of developmental changes and life events that occur over time with minimal burden to participating youth and parents. Intensive efforts are made to keep the vast majority of participants involved with the study through adolescence and beyond, and retention rates thus far are very high. Neuroimaging has expanded our understanding of brain development from childhood into adulthood. Using this and other cutting-edge technologies, ABCD can determine how different kinds of youth experiences (such as sports, school involvement, extracurricular activities, videogames, social media, unhealthy sleep patterns, and vaping) interact with each other and with a child?s changing biology to affect brain development and social, behavioral, academic, health, and other outcomes. Data, securely and privately shared with the scientific community, will enable investigators to: (1) describe individual developmental pathways in terms of neural, cognitive, emotional, and academic functioning, and influencing factors; (2) develop national standards of healthy brain development; (3) investigate the roles and interaction of genes and the environment on development; (4) examine how physical activity, sleep, screen time, sports injuries (including traumatic brain injuries), and other experiences influence brain development; (5) determine and replicate factors that influence mental health from childhood to young adulthood; (6) characterize relationships between mental health and substance use; and (7) specify how use of substances such as cannabis, alcohol, tobacco, and caffeine affects developmental outcomes, and how neural, cognitive, emotional, and environmental factors influence the risk for adolescent substance use.