Depression and social anxiety are highly impairing disorders that often co-occur and are twice as frequent in women compared to men. These problems are common in adolescents with earlier symptoms of anxiety, but tend to emerge or increase during adolescence, especially in girls. Depression is known to be associated with reduced positive affect/reward responsiveness, and growing evidence indicates that individuals with social anxiety also show reduced positive affect. We test a model proposing that sensitivity to social threat during early adolescence leads to blunted responsiveness to social rewards in the environment, which in turn contributes to increases in social anxiety and depressive symptoms later in adolescence. A large body of research shows that youth with high levels of fearful temperament or trait anxiety display increased vigilance for threatening stimuli, especiall stimuli conveying potential social threat. Girls appear to be particularly sensitive to interpersonl threats. In animal studies, exposure to social threats leads to dopaminergic changes and blunted responsiveness to reward. Yet, little is known about how social threats contribute to reward functioning in human adolescents, particularly during the period surrounding pubertal maturation, when social threats become increasingly salient. We propose that early adolescent girls who are sensitive to social threat will exhibit increased activation to social threat in an affective salience network of ventral brain regions involved in attending to personally salient threats (e.g. amygdala, subgenual anterior cingulate cortex, medial prefrontal cortex, anterior insula, and nucleus accumbens). This reactivity will contribute to a behavioral tendency to avoid situations that carry potential for social threat even when these situations also carry potential fr reward (i.e. making new friends, trying a new activity). Over time, increased neural reactivity to social threats and associated behavioral avoidance of possible threatening scenarios could alter reward responsiveness through several inter- related mechanisms, including: (a) reduced striatal response to reward (b) reduced social approach motivation, (c) reduced attention toward social reward cues, and/or (d) reduced subjective experience of positive emotion during social interactions. These changes are proposed to play a role in the emergence and exacerbation of symptoms. We test this model in a longitudinal study of early adolescent girls oversampled for subthreshold symptoms of social anxiety at baseline. The study will include neuroimaging during simulated peer interaction tasks that probe neural response to social threat and reward, behavioral and eye tracking paradigms, and Eco- logical Momentary Assessment (EMA) of daily social interactions, along with concurrent assessment of clinical symptoms and pubertal hormones. The battery will be completed at baseline (T1; ages 11-13) and 2 years later (T2; ages 13-15), with an additional clinical assessment at T3 (ages 14-16). Results are expected to high- light potentially modifiable shared neurobehavioral risk factors for social anxiety and depression in girls that could be targeted through neuroscience-based interventions during a sensitive developmental window.

Public Health Relevance

Depression and social anxiety disorders are co-occurring serious mental illnesses that typically emerge during adolescence, especially in girls, and pose tremendous cost to society in both human suffering and financial burden across the lifespan. Existing treatments for these disorders primarily target neural circuits and behaviors involved in responding to negative emotions, but as many as half of youth don't respond fully to these treatments, thus alternative intervention targets grounded in developmental neuroscience are needed. We identify developmental alterations in the RDoC Positive Valence System that are proposed to occur during adolescence among youth who are sensitive to negative social evaluation as a way to inform the development of personalized and developmentally-tuned interventions for social anxiety and depression that target reward- related neural function, attention, and behavior.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Psychosocial Development, Risk and Prevention Study Section (PDRP)
Program Officer
Zehr, Julia L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Schools of Medicine
United States
Zip Code
Guyer, Amanda E; Silk, Jennifer S; Nelson, Eric E (2016) The neurobiology of the emotional adolescent: From the inside out. Neurosci Biobehav Rev 70:74-85