Probing the Neural Correlates of Anticipated Peer Evaluation in Adolescence

Neural correlates of social cognition were assessed in 9-to-17-year-olds using functional magnetic resonance imaging (fMRI). 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

Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex

Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and 12 age-, gender- and IQ-matched, psychiatrically-healthy adolescents received ‘not interested’ and ‘interested’ feedback from unknown peers during a Chatroom task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high desirability ratings. Further highlighting the salience of such feedback, all adolescents, independent of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety

A Developmental Examination of Amygdala Response to Facial Expressions

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

Recognition of facial emotions among maltreated children with high rates of post–traumatic stress disorder

Objective. The purpose of this study is to examine processing of facial emotions in a sample of maltreated children showing high rates of post-traumatic stress disorder (PTSD). Maltreatment during childhood has been associated independently with both atypical processing of emotion and the development of PTSD. However, research has provided little evidence indicating how high rates of PTSD might relate to maltreated children’s processing of emotions. Method. Participants’ reaction time and labeling of emotions were measured using a morphed facial emotion identification task. Participants included a diverse sample of maltreated children with and without PTSD and controls ranging in age from 8 to 15 years. Maltreated children had been removed from their homes and placed in state custody following experiences of maltreatment. Diagnoses of PTSD and other disorders were determined through combination of parent, child, and teacher reports. Results. Maltreated children displayed faster reaction times than controls when labeling emotional facial expressions, and this result was most pronounced for fearful faces. Relative to children who were not maltreated, maltreated children both with and without PTSD showed enhanced response times when identifying fearful faces. There was no group difference in labeling of emotions when identifying different facial emotions. Conclusions. Maltreated children show heightened ability to identify fearful faces, evidenced by faster reaction times relative to controls. This association between maltreatment and atypical processing of emotion is independent of PTSD diagnosis

Specificity of facial expression labeling deficits in childhood psychopathology

Background: We examined whether face-emotion labeling deficits are illness-specific or an epiphenomenon of generalized impairment in pediatric psychiatric disorders involving mood and behavioral dysregulation. Method: Two hundred fifty-two youths (7-18 years old) completed child and adult facial expression recognition subtests from the Diagnostic Analysis of Nonverbal Accuracy (DANVA) instrument. Forty-two participants had bipolar disorder (BD), 39 had severe mood dysregulation (SMD; i.e., chronic irritability, hyperarousal without manic episodes), 44 had anxiety and/or major depressive disorders (ANX/MDD), 35 had attention-deficit/hyperactivity and/or conduct disorder (ADHD/CD), and 92 were controls. Dependent measures were number of errors labeling happy, angry, sad, or fearful emotions. Results: BD patients made more errors than ANX/MDD, ADHD/CD, or controls when labeling all emotional expressions, whether those expressions were on the faces of children or adults. SMD also showed emotion-labeling deficits, in particular as compared to ANX/MDD patients and controls. Conclusions: Face-emotion labeling deficits differentiate BD and SMD patients from those with ANX/MDD or ADHD/CD and controls. The extent to which such deficits cause vs. result from emotional dysregulation requires further study

Common and specific amygdala-function perturbations in 2 depressed versus anxious adolescents

Context: Few studies directly compare amygdala function in depressive and anxiety disorders. 43 Data from longitudinal research emphasize the need for such studies in adolescents. 44 Objective: To compare amygdala response to varying attention and emotion conditions among 45 adolescents with Major Depressive Disorder (MDD) or anxiety disorders, relative to adolescents 46 with no psychopathology. 47 Design: Case-Control-Study. 48 Setting: Government Clinical Research Institute. 49 Participants: Eighty-seven adolescents matched on age, gender, intelligence, and social class: 26 50 with Major Depressive Disorder (MDD; 14 with and 12 without anxiety disorders), 16 with 51 anxiety disorders but no depression, and 45 with no psychopathology. 52 Main Outcome Measures: Blood oxygenated level dependent signal in the amygdala, measured 53 using event-related functional magnetic resonance imaging. During imaging, participants viewed 54 facial expressions (neutral, fearful, angry, happy) while attention was constrained (afraid, 55 hostility, nose width ratings) or unconstrained (passive-viewing). 56 Results: Left and right amygdala activation differed as a function of diagnosis, facial expression, 57 and attention-condition both when comorbid MDD/anxiety patients were included and excluded 58 (group-by-emotion-by-attention interactions: p-values≤.03). Focusing on fearful-face-viewing 59 events, anxiety and MDD patients both differed in amygdala responses from healthy participants 60 and from each other during passive-viewing. However, both MDD and anxiety patients, relative 61 to healthy participants, exhibited similar signs of amygdala hyper-activation to fearful faces when 62 rating subjectively experienced fear. 63 Conclusions: Adolescent MDD and anxiety disorders exhibit common and distinct functional 64 neural correlates during face processing. Attention modulates the degree to which common or 65 distinct amygdala perturbations manifest in these patient groups, relative to healthy peers

Emotional orientation, brain function and genetics in adults and children : implications for development, and psychopathology

The ability to attend or avoid emotional stimuli is important to our survival. Attending to potential threats can help us avoid danger; while attending to positive stimuli is important for our social function. For example, when we see a man with a knife it is important to run away, or avoid the threat so we are not harmed. Just as the knife warns us of the threatening stiuation, a smiling face indicates a friendly person. We are drawn to this cue to possibly receive a rewarding social interaction. Attention orientation to both negative and positive stimuli may be impacted by development, psychopathology and genetics. The dot probe task yields both behavioral and neural indices of attention biases towards or away from an emotional cue (angry or happy face). This thesis includes three studies to determine the effects of development, psychopathology, and genetics on attention orientating. In Study I, we examined age-related correlations in attention-orienting biases to negative and positive faces in a healthy sample using functional magnetic resonance imaging (fMRI) and a dot probe task. Behavioral response data indicated a positive correlation between age and attention bias towards happy faces, such that younger participants showed less bias towards happy, relative to neutral, faces, than older subjects. Attention bias towards angry faces did not correlate with age. Relative to older, younger participants demonstrated greater activation in the left cuneus and left caudate on the contrast of trials used to assess happy-face attention bias. In Study II, using the dot probe task in a home setting, we studied parents that were highly exposed to the attack on the World Trade Center in 2001 and their children. We found that psychiatrically healthy parents who experienced severe trauma showed greater attention bias towards threat than parents experiencing no such trauma, but trauma experienced by parents did was not predictive of attention bias in their children. In Study III, using an fMRI on 5-HTTLPR genotyped adults performing dot probe task; we compared amygdala response to threat bias contrasts. The 5- HTTLPR has been previously linked to amygdala reactivity and the amygdala has been implicated in the orienting of attention towards threat. Behavioral data indicated no difference between the two genotyped subject populations for the 5-HTTLPR polymorphism (l/l and s-carrier). However, fMRI data did reveal between-group differences in the amygdala activation. Specifically, relative to l/l, s-carriers showed greater right amygdala activation to trials with angry faces. Because similar levels of threat bias were found in the two genotype groups, these findings suggest that s-carriers exhibit a lower threshold for engaging the amygdala within the context of the task. In total, these three studies explore the effect of both the environment and genes on behavior and brain function. Studies I and II focus on environment, specifically, how their environment affects their emotional orientation. On the genetic side, Study III focuses on the effect of genetics on emotional orientation

Amygdala and Ventrolateral Prefrontal Cortex Function during Anticipated Peer Evaluation in Pediatric Social Anxiety

1. Context. Amygdala and ventrolateral prefrontal cortex 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. 2. Objective. To determine whether photographs of negatively-evaluated smiling peers, viewed during anticipated evaluation, engage the amygdala and ventrolateral prefrontal cortex differentially in adolescents with and without social anxiety. 3. Design. Case-control study. 4. Setting. Government clinical research institute. 5. Participants. Fourteen adolescents with anxiety disorders associated with marked social concerns and 14 diagnosis-free adolescents, matched on sex, age, IQ, and socio-economic status. 6. Main Outcome Measure(s). 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. 7. Results. Participants classified 40 pictures of same-age peers as ones they wanted to engage or not engage with for a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers rated as undesired for an interaction. Viewing undesired peers engaged stronger positive amygdala-ventrolateral-prefrontal-cortex connectivity in anxious vs. healthy adolescents. 8. Conclusions. Anticipating social evaluation from negatively-perceived peers modulates amygdala and ventrolateral prefrontal cortex engagement differentially in anxious and healthy 3 adolescents. Amygdala and ventrolateral prefrontal cortex abnormalities in adolescent anxiety disorders are heightened in specific contexts of potential peer evaluation

Immunization coverage and risk factors for failure to immunize within the Expanded Programme on Immunization in Kenya after introduction of new Haemophilus influenzae type b and hepatitis b virus antigens

Background: Kenya introduced a pentavalent vaccine including the DTP, Haemophilus influenzae type b and hepatitis b virus antigens in Nov 2001 and strengthened immunization services. We estimated immunization coverage before and after introduction, timeliness of vaccination and risk factors for failure to immunize in Kilifi district, Kenya. Methods: In Nov 2002 we performed WHO cluster-sample surveys of > 200 children scheduled for vaccination before or after introduction of pentavalent vaccine. In Mar 2004 we conducted a simple random sample (SRS) survey of 204 children aged 9 - 23 months. Coverage was estimated by inverse Kaplan-Meier survival analysis of vaccine- card and mothers' recall data and corroborated by reviewing administrative records from national and provincial vaccine stores. The contribution to timely immunization of distance from clinic, seasonal rainfall, mother's age, and family size was estimated by a proportional hazards model. Results: Immunization coverage for three DTP and pentavalent doses was 100% before and 91% after pentavalent vaccine introduction, respectively. By SRS survey, coverage was 88% for three pentavalent doses. The median age at first, second and third vaccine dose was 8, 13 and 18 weeks. Vials dispatched to Kilifi District during 2001 - 2003 would provide three immunizations for 92% of the birth cohort. Immunization rate ratios were reduced with every kilometre of distance from home to vaccine clinic (HR 0.95, CI 0.91 - 1.00), rainy seasons ( HR 0.73, 95% CI 0.61 - 0.89) and family size, increasing progressively up to 4 children ( HR 0.55, 95% CI 0.41 - 0.73). Conclusion: Vaccine coverage was high before and after introduction of pentavalent vaccine, but most doses were given late. Coverage is limited by seasonal factors and family siz