Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene.

Recent evidence suggests that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTTLPR allelic variation and responses to fearful and angry faces presented both sub- and supraliminally in participants, ages 9-17. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to fearful and angry faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults. These results indicate that in children and adolescents, s-allele carriers can be distinguished from l-allele homozygotes on the basis of hypervigilant behavioral and neural processing of negative material.

Neural circuitry of emotional face processing in autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. METHODS: Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. RESULTS: In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. LIMITATIONS: The small sample size may have affected our ability to detect additional group differences. CONCLUSION: When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.

Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder.

CONTEXT: Vigilance for threat is a key feature of generalized anxiety disorder (GAD). The amygdala and the ventrolateral prefrontal cortex constitute a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly presented threats in GAD or in pediatric anxiety. OBJECTIVE: To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis. MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging to measure blood oxygenation level-dependent signal. During imaging, subjects performed an attention-orienting task with rapidly presented (17 milliseconds) masked emotional (angry or happy) and neutral faces. RESULTS: When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects. CONCLUSIONS: 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.