A developmentally-sensitive mechanism underlying the escalation of adolescent social anxiety

Abstract
Social anxiety disorder (SAD) is a chronic, impairing condition that typically emerges during adolescence and
affects about 10% of the population. Treatment response rates for SAD are markedly lower than for other anxiety
disorders, thus presenting an urgent need to identify novel therapeutic targets that can inform new interventions
for this difficult-to-treat disorder. We propose to address this need by testing a developmentally-informed,
mechanistic model of the escalation of impairing social anxiety symptoms (SA) in early-to-mid adolescence; our
model centers on Fear of Negative Evaluation (FNE) and Hypervigilance for Errors in the presence of peers, with
a focus on frontal brain oscillations as central to this escalation. Adolescence represents a sensitive period for
the development of social cognition and cognitive control. At the psychological level, social fears and FNE exhibit
normative increases across adolescence, given the increasing importance of peers during this developmental
window. At the neural level, frontal brain systems underlying social cognition and cognitive control exhibit
protracted development across adolescence, including development of the frontal cortex and associated 4-8 Hz
“theta” oscillations causally implicated in cognitive control. Our central hypothesis is that adolescent increases
in FNE, alongside development of the frontal cortex, create a maladaptive feedback loop: adolescents become
Hypervigilant to Errors in social settings, further increasing FNE, and ultimately, impairing SA. Our model predicts
(Aim 1) that developmental increases in FNE lead to increased concerns over performance in the presence of
peers, which in turn amplifies Hypervigilance for Errors (that is, increased strength of error-related theta
oscillations). We further predict (Aim 2) that increased Hypervigilance for Errors leads to more critical self-
evaluations and confirmations of initial fears, which worsen FNE/SA over time. Moreover, we predict adolescents
who exhibit greater synchrony in theta oscillations across medial-lateral frontal cortex are at greatest risk and
will display the largest increases in FNE/SA. To test our model, we will collect an accelerated longitudinal study
of 256 adolescents, spanning ages 11-15, biologically male/female, and ranging in FNE/SA. Participants will
complete a modified cognitive control task in peer presence/absence (via Zoom) as EEG is recorded. With an
eye toward future translational work, we will also (Aim 3) establish the ecological validity of our neural measures
by testing links to micro-coded behaviors indicative of SA within a social interaction task. Given that escalation
of SA occurs during puberty and within a broader social context, we will also measure, control for, and explore
the possible moderating roles of puberty, as well as effects of social and demographic variables. A key strength
of this proposal is that our team has a proven record in developmental psychopathology and experimental
therapeutics, providing a clear path for translating findings from this project into novel, brain-based therapeutics
and thereby shortening the distance “from bench to bedside.”

Grant Number: 5R01MH131637-04
NIH Institute/Center: NIH
Principal Investigator: George Buzzell