Neural, Physiological, Behavioral, and Environmental Risk Markers of Anxiety from Infancy to Adolescence

PROJECT SUMMARY/ABSTRACT
Anxiety disorders are the most common psychiatric illnesses and are often resistant to treatment. Adolescence
is a core risk period for the development and exacerbation of anxiety, which often has a chronic course,
negatively affecting academic, social, and adaptive functioning, and increasing the risk for mental illness
through adulthood. Research has highlighted a number of risk factors that likely contribute to the development
and maintenance of anxiety. However, there is limited understanding of the earliest precursors of anxiety or
how multiple risk factors interact within and across development to influence anxiety risk. Prospective studies
beginning in infancy are needed to explicate the origins of anxiety so that (a) biomarkers can be discovered
that identify at-risk youth prior to the emergence of symptoms and (b) preventive strategies can be developed
and implemented with those at risk. The overall goal of the current project is to test the combined effects of
neural, physiological, behavioral, and environmental risk factors on anxiety from infancy through adolescence.
The study aims will be accomplished by following our established longitudinal cohort (R01 MH078829; N=807),
who have provided a rich dataset, including repeated assessments of neurophysiology (EEG, ERP),
physiological stress reactivity, behavioral indicators of threat reactivity, and environmental risk (e.g., maternal
psychopathology, negative life events, COVID-19 related stressors) between infancy and age 7 years. In the
current proposal, we seek funds to support a follow-up study to age 13 years. We will phenotype our cohort for
anxiety symptomatology and diagnoses, across multiple phenotypes, and implement a battery of brain-based
measures, physiological and behavioral protocols, and assessments of environmental exposures, including
exposures of particular relevance in adolescence and exposures related to the COVID-19 pandemic. We will
apply a combination of established and novel analysis approaches to develop diagnostic neural biomarkers of
anxiety in adolescence; identify positive and negative environmental characteristics that influence anxiety-
relevant neural signatures in adolescence, that affect anxiety-related neural trajectories from infancy to
adolescence, and that moderate the effects of neural reactivity on anxiety risk; determine how COVID-19
related stressors interact with childhood pre-pandemic characteristics (neural and behavioral threat reactivity,
physiological stress reactivity) to influence adolescent anxiety risk; and to develop assay profiles comprising
neural, physiological, behavioral, and/or environmental characteristics from infancy through adolescence that
robustly predict anxiety trajectories across development. We expect that the findings will (a) improve our
understanding of the neural circuitry underlying anxiety risk in youth, (b) contribute to the discovery of robust
developmentally-informed multi-modal profiles that can identify at-risk children, and (c) inform the design of
innovative strategies to prevent the emergence of anxiety and to treat more precisely symptomatic youth by
addressing and correcting atypical neural processes and their downstream behavioral manifestations.

Grant Number: 5R01MH078829-28
NIH Institute/Center: NIH
Principal Investigator: Michelle Bosquet Enlow