Vigilance for threat represents a prominent feature of generalized anxiety disorder (GAD).^1-4 Neuroimaging research implicates a neural circuit that includes the amygdala and the ventrolateral prefrontal cortex in vigilance for threat.^4-7 Within this circuit, the amygdala is thought to support vigilance through immediate threat processing,^8,9 whereas the ventrolateral prefrontal cortex facilitates later processes related to emotion regulation.^5,10 Disturbed amygdala–ventrolateral prefrontal cortex interactions are thought to influence anxiety.¹⁰

Dramatic changes in the social context of behavior during adolescence are associated with increased incidence of social anxiety.^1-4 Information-processing biases about social experiences may contribute to this increase in anxiety. For example, psychological theories posit that social anxiety is associated with excessive fears of judgment and biased appraisals of others as overly critical.^5,6 These theories suggest that anticipation of peer evaluation leads anxious adolescents to misperceive peers as overly threatening and uninterested in social interactions with them. Functional neuroimaging provides an opportunity to ground these psychological theories in knowledge of neural function.⁷

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.

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.