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Erin B. McClure, PhD; Christopher S. Monk, PhD; Eric E. Nelson, PhD; Jessica M. Parrish, BA; Abby Adler, BA; R. James R. Blair, PhD; Stephen Fromm, PhD; Dennis S. Charney, MD; Ellen Leibenluft, MD; Monique Ernst, MD, PhD; Daniel S. Pine, MD

Arch Gen Psychiatry. 2007;64(1):97-106.

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.

Author Affiliations: Emotional Development and Affective Neuroscience Branch (Drs McClure, Nelson, Ernst, and Pine and Mss Parrish and Adler) and Unit on Affective Disorders, Pediatrics and Developmental Neuropsychiatry Branch (Dr Leibenluft), Mood and Anxiety Disorders Program (Drs Blair and Fromm), National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Md; Department of Psychology, Georgia State University, Atlanta (Dr McClure); Department of Psychology and Center for Human Growth and Development, University of Michigan at Ann Arbor (Dr Monk); and Departments of Psychiatry, Neuroscience, and Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY (Dr Charney).

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