Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.

Objective. Offspring of parents with major depressive disorder (MDD) face three-fold higher risk for MDD than offspring without a family history. Although MDD is a major cause of morbidity and mortality, neural correlates of risk for MDD remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for MDD under varying attentional and emotional conditions. Methods. Thirty-nine juveniles, 17 offspring of parents with MDD (high-risk group) and 22 offspring of parents without histories of MDD, anxiety or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials; while attention was unconstrained (passive viewing), and constrained (rate nose width on face; rate subjective fear while viewing face). Results. When attention was unconstrained, high-risk, relative to lowrisk, subjects showed greater amygdala and nucleus accumbens (NAcc)

Context Amygdala and ventrolateral prefrontal cortex (vlPFC) dysfunction manifests in adolescents with anxiety disorders when they view negatively valenced stimuli in threatening contexts. Such fear-circuitry dysfunction may also manifest when anticipated social evaluation leads socially anxious adolescents to misperceive peers as threatening. Objective To determine whether photographs of negatively evaluated smiling peers viewed during anticipated social evaluation engage the amygdala and vlPFC differentially in adolescents with and without social anxiety. Design Case-control study. Setting Government clinical research institute. Participants Fourteen adolescents with anxiety disorders associated with marked concerns of social evaluation and 14 adolescents without a psychiatric diagnosis matched on sex, age, intelligence quotient, and socioeconomic status. Main Outcome Measures Blood oxygenation level–dependent signal measured with event-related functional magnetic resonance imaging. Before and during neuroimaging scans, participants anticipating social evaluation completed peer- and self-appraisals. Event-related analyses were tailored to participants’ ratings of specific peers. Results Participants classified 40 pictures of same-age peers as ones with whom they did or did not want to engage in a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers previously rated as undesired for an interaction. Psychophysiological interaction connectivity analyses also revealed a significant positive association between amygdala and vlPFC activation in anxious vs healthy adolescents in response to these stimuli. Conclusions Anticipating social evaluation from negatively perceived peers modulates amygdala and vlPFC engagement differentially in anxious and healthy adolescents. Amygdala and vlPFC dysfunction manifests in adolescent anxiety disorders in specific contexts of anticipated peer evaluation.

Several lines of evidence implicate the amygdala in face-emotion processing, particularly for fearful facial expressions. Related findings suggest that face-emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala's response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9-17 years old) and 30 adults (21-40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala-hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions.

Context Few studies directly compare amygdala function in depressive and anxiety disorders. Data from longitudinal research emphasize the need for such studies in adolescents. Objective To compare amygdala response to varying attention and emotion conditions among adolescents with major depressive disorder (MDD) or anxiety disorders, relative to adolescents with no psychopathology. Design Case-control study. Setting Government clinical research institute. Participants Eighty-seven adolescents matched on age, sex, intelligence, and social class: 26 with MDD (14 with and 12 without anxiety disorders), 16 with anxiety disorders but no depression, and 45 without psychopathology. Main Outcome Measures Blood oxygen level–dependent signal in the amygdala, measured by means of event-related functional magnetic resonance imaging. During imaging, participants viewed facial expressions (neutral, fearful, angry, and happy) while attention was constrained (afraid, hostility, and nose-width ratings) or unconstrained (passive viewing). Results Left and right amygdala activation differed as a function of diagnosis, facial expression, and attention condition both when patients with comorbid MDD and anxiety were included and when they were excluded (group × emotion × attention interactions, P≤.03). Focusing on fearful face–viewing events, patients with anxiety and those with MDD both differed in amygdala responses from healthy participants and from each other during passive viewing. However, both MDD and anxiety groups, relative to healthy participants, exhibited similar signs of amygdala hyperactivation to fearful faces when subjectively experienced fear was rated. Conclusions Adolescent MDD and anxiety disorders exhibit common and distinct functional neural correlates during face processing. Attention modulates the degree to which common or distinct amygdala perturbations manifest in these patient groups, relative to healthy peers.

Neural correlates of social-cognition were assessed in 9-to-17-year-olds (N = 34) using functional magnetic resonance imaging. Participants appraised how unfamiliar peers they had previously identified as being of high or low interest would evaluate them for an anticipated online chat session. Differential age-and sexrelated activation patterns emerged in several regions previously implicated in affective processing. These included the ventral striatum, hippocampus, hypothalamus, and insula. In general, activation patterns shifted with age in older relative to younger females but showed no association with age in males. Relating these neural response patterns to changes in adolescent social-cognition enriches theories of adolescent social development through enhanced neurobiological understanding of social behavior.

Objective-To examine attention bias towards threat faces in a large sample of anxiety-disordered youths using a well-established visual probe task.Method-Study participants included 101 children and adolescents (ages 7-18 years) with generalized anxiety disorder, social phobia and/or separation anxiety disorder enrolled in a multisite anxiety treatment study. Non-anxious youths (n = 51; ages 9 -18 years) were recruited separately. Participants were administered a computerized visual probe task that presents pairs of faces portraying threat (angry), positive (happy) and neutral expressions. They pressed a response-key to indicate the spatial location of a probe that replaced one of the faces on each trial. Attention bias scores were calculated from response times to probes for each emotional face type.Results-Compared to healthy youths, anxious participants demonstrated a greater attention bias towards threat faces. This threat bias in anxious patients did not significantly vary across the anxiety disorders. There was no group difference in attention bias towards happy faces.Conclusions-These results suggest that pediatric anxiety disorders are associated with an attention bias towards threat. Future research might examine the manner in which cognitive bias in anxious youth changes with treatment.

Background Post-traumatic stress disorder (PTSD) develops in a minority of traumatized individuals. Attention biases to threat and abnormalities in fear learning and extinction are processes likely to play a critical role in the creation and/or maintenance of PTSD symptomatology. However, the relationship between these processes has not been established, particularly in highly traumatized populations; understanding their interaction can help inform neural network models and treatments for PTSD. Method Attention biases were measured using a dot probe task modified for use with our population; task stimuli included photographs of angry facial expressions, which are emotionally salient threat signals. A fear-potentiated startle paradigm was employed to measure atypical physiological response during acquisition and extinction phases of fear learning. These measures were administered to a sample of 64 minority (largely African American), highly traumatized individuals with and without PTSD. Results Participants with PTSD demonstrated attention biases toward threat; this attentional style was associated with exaggerated startle response during fear learning and early and middle phases of extinction, even after accounting for the effects of trauma exposure. Conclusions Our findings indicate that an attentional bias toward threat is associated with abnormalities in ‘ fear load ’ in PTSD, providing seminal evidence for an interaction between these two processes. Future research combining these behavioral and psychophysiological techniques with neuroimaging will be useful toward addressing how one process may modulate the other and understanding whether these phenomena are manifestations of dysfunction within a shared neural network. Ultimately, this may serve to inform PTSD treatments specifically designed to correct these atypical processes.