Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex.

Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and 12 age-, gender- and IQ-matched, psychiatrically-healthy adolescents received 'not interested' and 'interested' feedback from unknown peers during a Chatroom task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high desirability ratings. Further highlighting the salience of such feedback, all adolescents, independent of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety.

Responses to conflict and cooperation in adolescents with anxiety and mood disorders.

This study examined patterns of behavioral and emotional responses to conflict and cooperation in adolescents with anxiety/mood disorders and healthy peers. We compared performance on and emotional responses to the Prisoner's Dilemma (PD) game, an economic exchange task involving conflict and cooperation, between adolescents with anxiety/depressive disorders (A/D) (N=21) and healthy comparisons (n = 29). Participants were deceived to believe their co-player (a pre-programmed computer algorithm) was another study participant. A/D adolescents differed significantly from comparisons in patterns of play and emotional response to the game. Specifically, A/D participants responded more cooperatively to cooperative overtures from their co-players; A/D girls also reported more anger toward co-players than did comparison girls. Our findings indicate that A/D adolescents, particularly females, respond distinctively to stressful social interchanges. These findings offer a first step toward elucidating the mechanisms underlying social impairment in youth with internalizing disorders.

Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.

CONTEXT: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. OBJECTIVE: To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Fifteen adolescents with generalized anxiety disorder and 20 controls. MAIN OUTCOME MEASURES: Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. RESULTS: While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex. CONCLUSIONS: This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.