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Humans' experience of emotion and comprehension of affective cues varies substantially across the lifespan. Work in cognitive and affective neuroscience has begun to characterize behavioral and neural responses to emotional cues that systematically change with age. This review examines work to date characterizing the maturation of facial expression comprehension, and dynamic changes in amygdala recruitment from early childhood through late adulthood while viewing facial expressions of emotion. Recent neuroimaging work has tested amygdala and prefrontal engagement in experimental paradigms mimicking real aspects of social interactions, which we highlight briefly, along with considerations for future research.

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We compared neural and behavioral responses to feedback received during interpersonal interactions within the Prisoner's Dilemma game between adolescents with anxiety disorders (n = 12) and healthy peers (n = 17). Groups differed significantly in neural activation in the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), precuneus, insula, and temporoparietal junction (TPJ). Anxious adolescents were also more likely than controls to cooperate after co-player betrayal. Our findings provide evidence that social behavior and related neural activity differs between anxious and healthy adolescents. These findings constitute a step toward elucidating neural correlates of social impairment in anxious youths.

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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 sex-related 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.

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Cognitive-perceptual, interpersonal, and disorganized subscales of the Schizotypal Personality Questionnaire-Brief (SPQ-B), reflecting the three commonly used subscales of the full-version SPQ, have been used in a number of studies. However, the factorial validity of SPQ-B subscales remains to be clarified. Utilizing data from 825 undergraduate students, confirmatory factor analyses involving the 22 items of the SPQ-B were conducted. A significant chi(2) difference test favored the 3-factor over the 1-factor model and fit indices for the 3-factor model were generally satisfactory. However, several of the items may index more than one of the hypothesized factors, so the item-factor separation is not sharp. Thus, more research is needed on the factorial validity of the increasingly used SPQ-B subscales.

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OBJECTIVE: Although several exploratory and confirmatory factor analyses have supported the initially proposed factor structure of the Schizotypal Personality Questionnaire (SPQ) in which its nine subscales are grouped into cognitive-perceptual, interpersonal, and disorganized domains, others have revealed different latent structures. This study determined the best-fitting factor structure from among five models that have been proposed in the literature, as well as five additional hierarchically related models. METHODS: Undergraduate college students (n=825) completed the SPQ as well as the Perceptual Aberration Scale (PAS) and the Revised Social Anhedonia Scale (SAS). Confirmatory factor analyses involving the nine SPQ subscales were conducted using the Linear Structural Relations Program (LISREL 8.72). RESULTS: The best fitting model was a previously described 4-factor model including cognitive-perceptual, paranoid, negative, and disorganized domains. Correlations between the derived SPQ domains and the PAS score ranged r=.26-.39, and correlations between the SPQ domains and the SAS ranged r=.07-.41. CONCLUSIONS: The present findings support a 4-factor model over the standard 3-factor model that is typically used to derive SPQ subscale scores. The four derived domains are minimally to moderately correlated with other measures of psychosis-proneness.

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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 x emotion x attention interactions, P < or = .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.

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Schizotypy is a multidimensional personality construct that is characterized by perceptual abnormalities, social withdrawal, mild suspiciousness, and odd thinking patterns. This study examined the relationship between four dimensions of self-reported schizotypy and substance use involving nicotine, alcohol, and cannabis, in undergraduate students. Results showed that higher levels of disorganized schizotypy, or odd thinking and behavior, were associated with greater indices of use of all three substances. Furthermore, higher cognitive-perceptual schizotypy was selectively associated with cannabis use. Results confirm findings of recent research that has discovered associations among schizotypy and substance use, highlighting links between behavioral traits and use of nicotine, alcohol, and cannabis. This study is one of the first to examine a wide range of schizotypy domains, and to show selective effects of the disorganized domain of schizotypy.

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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.

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OBJECTIVE: To examine attention bias toward 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. Nonanxious 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 toward threat faces. This threat bias in anxious patients did not significantly vary across the anxiety disorders. There was no group difference in attention bias toward happy faces. CONCLUSIONS: These results suggest that pediatric anxiety disorders are associated with an attention bias toward threat. Future research may examine the manner in which cognitive bias in anxious youths changes with treatment.

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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.

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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.

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OBJECTIVE: Offspring of parents with major depressive disorder face a threefold higher risk for major depression than offspring without such family histories. Although major depression is a significant cause of morbidity and mortality, neural correlates of risk for major depression remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for major depression under varying attentional and emotional conditions. METHOD: Thirty-nine juveniles, 17 offspring of parents with major depression (high-risk group) and 22 offspring of parents without histories of major depression, 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 subjects showed greater amygdala and nucleus accumbens activation to fearful faces and lower nucleus accumbens activation to happy faces (small volume corrected for the amygdala and nucleus accumbens). No group differences emerged in amygdala or nucleus accumbens activation during constrained attention. Exploratory analysis showed that constraining attention was associated with greater medial prefrontal cortex activation in the high-risk than in the low-risk group. CONCLUSIONS: Amygdala and nucleus accumbens responses to affective stimuli may reflect vulnerability for major depression. Constraining attention may normalize emotion-related neural function possibly by engagement of the medial prefrontal cortex; face-viewing with unconstrained attention may engage aberrant processes associated with risk for major depression.

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