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Facilitated attention toward angry stimuli (attention bias) may contribute to anger proneness and temper outbursts exhibited by children with high irritability. However, most studies linking attention bias and irritability rely on behavioral measures with limited precision and no studies have explored these associations in young children. The present study explores irritability-related attention biases toward anger in young children (N = 128; ages 4-7 years) engaged in a dot-probe task with emotional faces, as assessed with event-related brain potential (ERP) indices of early selective attention and multi-method assessment of irritability. Irritability assessed via semi-structured clinical interview predicted larger anterior N1 amplitudes to all faces. In contrast, irritability assessed via a laboratory observation paradigm predicted reduced P1 amplitudes to angry relative to neutral faces. These findings suggest that altered early attentional processing occurs in young children with high irritability; however, the nature of these patterns may vary with methodological features of the irritability assessments. Future investigations using different assessment tools may provide greater clarity regarding the underlying neurocognitive correlates of irritability. Such studies may also contribute to the ongoing debates about how to best define and measure irritability across the developmental spectrum in a manner that is most informative for linkage to neural processes.

OBJECTIVES Little is known about potential differences in the pathophysiology of bipolar disorder (BD) across development. The present study aimed to characterize age-related neural mechanisms of BD. METHODS Youths and adults with and without BD (N = 108, age range = 9.8-55.9 years) completed an emotional face labeling task during fMRI acquisition. We leveraged three different fMRI analytic tools to identify age-related neural mechanisms of BD, investigating (a) change in neural responses over the course of the task, (b) neural activation averaged across the entire task, and (c) amygdala functional connectivity. RESULTS We found converging Age Group × Diagnosis patterns across all three analytic methods. Compared to healthy youths vs adults, youths vs adults with BD show an altered pattern in response to repeated presentation of emotional faces in medial prefrontal, amygdala, and temporoparietal regions, as well as amygdala-temporoparietal connectivity. Specifically, medial prefrontal and lingual activation decreases over the course of repeated emotional face presentations in healthy youths vs adults but increases in youths with BD compared to adults with BD. Moreover, youths vs adults with BD show less medial prefrontal activation and amygdala-temporoparietal junction connectivity averaged over the task, but this difference is not found for healthy youths vs adults. CONCLUSION Although longitudinal confirmation and replication will be necessary, these findings suggest that neural development may be aberrant in BD and that some neural mechanisms mediating BD may differ in adults vs children with the illness.

Individuals with a behaviorally inhibited (BI) temperament are more likely to develop social anxiety. However, the mechanisms by which socially anxious behavior emerges from BI are unclear. Variation in different forms of top-down control, specifically executive functions (EF), may play distinct roles and characterize differential pathways to social anxiety. Here 291 children were assessed for BI in toddlerhood (ages 2 and 3), parent-reported inhibitory control and set shifting during middle childhood (age 7), and multidimensional assessment of socially anxious behavior completed during late childhood and early adolescence (ages 9 and 12). Structural equation modeling revealed that early variation in BI predicted the development of socially anxious behavior through either higher levels of parent-reported inhibitory control or lower levels of parent-reported set shifting. These data reinforce the notion that top-down control does not uniformly influence relations between temperament and socially anxious behavior. These data suggest novel approaches to thinking about the role of EFs and social anxiety outcomes as children approach adolescence.

Background Callous-Unemotional (CU) and psychopathic traits are consistently associated with impaired recognition of others' emotions, specifically fear and sadness. However, no studies have examined whether the association between CU traits and emotion recognition deficits is due primarily to genetic or environmental factors. Methods The current study used data from 607 Caucasian twin pairs (N = 1,214 twins) to examine the phenotypic and genetic relationship between the Inventory of Callous-Unemotional Traits (ICU) and facial emotion recognition assessed via the laboratory-based Facial Expression Labeling Task (FELT). Results The uncaring/callous dimension of the ICU was significantly associated with impaired recognition of happiness, sadness, fear, surprise, and disgust. The unemotional ICU dimension was significantly associated with improved recognition of surprise and disgust. Total ICU score was significantly associated with impaired recognition of sadness. Significant genetic correlations were found for uncaring/callous traits and distress cue recognition (i.e. fear and sadness). The observed relationship between uncaring/callous traits and deficits in distress cue recognition was accounted for entirely by shared genetic influences. Conclusions The results of the current study replicate previous findings demonstrating impaired emotion recognition among youth with elevated CU traits. We extend these findings by replicating them in an epidemiological sample not selected or enriched for pathological levels of CU traits. Furthermore, the current study is the first to investigate the genetic and environmental etiology of CU traits and emotion recognition, and results suggest genetic influences underlie the specific relationship between uncaring/callous traits and distress cue (fear/sadness) recognition in others.

Irritability is a prominent feature of chronic mental disorders and a developmental marker of their early emergence. The most salient feature of irritability in early childhood is temper tantrums. While temper tantrums are normative in young children, they can be clinically concerning when they are dysregulated, very frequent, and/or occur in unexpected contexts. The present study uses behavioral and event-related brain potential (ERP) measures to characterize the relationship between irritability and neural markers of response inhibition in very young children. Forty-six children (ages 4–7 years) completed a go/no-go task under nonfrustrating and frustrating conditions. ERPs elicited by go and no-go stimuli were examined as a function of frustration condition and irritability, operationalized via the well-validated Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB). Higher Temper Loss scores were associated with larger N2(no-go) amplitudes and reduced no-go accuracy during frustration. This suggests that higher levels of irritability corresponded with increased conflict monitoring and poorer task performance during frustration. These findings add to a developing literature identifying the neurocognitive markers of varying levels of irritability in young children.

The current study examined relations between behavioral inhibition (BI) assessed in toddlerhood (n=268) and attention biases (AB) to threat and positive faces and maternal reported anxiety assessed when children were 5 and 7-years old. Results revealed that BI predicted anxiety at age 7 in children with AB toward threat, away from positive, or with no bias, at age 7; BI did not predict anxiety for children displaying AB away from threat or toward positive. Five-year AB did not moderate the link between BI and 7-year anxiety. No direct association between AB and BI or anxiety was detected; moreover, children did not show stable AB across development. These findings extend our understanding of the developmental links between BI, AB, and anxiety.

Background Irritability, a frequent complaint in children with psychiatric disorders, reflects increased predisposition to anger. Preliminary work in pediatric clinical samples links irritability to attention bias to threat, and the current study examines this association in a large population-based sample. Methods We studied 1,872 children (ages 6–14) using the Development and Well-Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL), and dot-probe tasks. Irritability was defined using CBCL items that assessed temper tantrums and hot temper. The dot-probe task assessed attention biases for threat-related (angry face) stimuli. Multiple regression analysis was used to assess specificity of associations to irritability when adjusting for demographic variables and co-occurring psychiatric traits. Propensity score matching analysis was used to increase causal inference when matching for demographic variables and co-occurring psychiatric traits. Results Irritability was associated with increased attention bias toward threat-related cues. Multiple regression analysis suggests associations between irritability and threat bias are independent from demographic variables, anxiety, and externalizing traits (attention-deficit/hyperactivity, conduct, and headstrong/hurtful), but not from broad internalizing symptoms. Propensity score matching analysis indicated that this association was found for irritable versus nonirritable groups matched on demographic and co-occurring traits including internalizing symptoms. Conclusions Irritability in children is associated with biased attention toward threatening information. This finding, if replicated, warrants further investigation to examine the extent to which it contributes to chronic irritability and to explore possible treatment implications.

Background Attention bias modification treatment (ABMT) targets threat-related attention biases in anxiety disorders. Most clinical trials of ABMT have focused on adults or small samples of youth. The current randomized controlled trial (RCT) examines ABMT efficacy in youth with social anxiety disorder (SAD) and tests possible moderators of treatment outcomes. Method Sixty-seven youth with SAD were randomly assigned to ABMT or attention control training (ACT) conditions. Anxiety severity was measured at baseline, posttreatment, and 3-month follow-up. ClinicalTrials.gov name and identifier: Attention bias modification treatment for children with social anxiety, NCT01397032; http://www.clinicaltrials.gov. Results Both ABMT and ACT induced significant reductions in clinician and self-rated social anxiety (ps

BACKGROUND: Threat-related attention bias relates to anxiety and posttraumatic stress symptoms in adults and adolescents, but few longitudinal studies examine such associations in young children. This study examines prospective relations among attention bias, trauma exposure, and anxiety and trauma symptoms in a sample previously reported to manifest cross-sectional associations between attention bias and observed anxiety at preschool age. METHODS: Young children [mean (MN) = 5.0, ±0.7 years, n = 208] from a community-based sample completed the dot-probe task to assess their attention biases in response to angry faces. At baseline (T1) and at follow-up approximately 9 months later (T2), anxiety and trauma exposure (i.e. violent and noninterpersonal events) and symptoms were assessed by maternal report. RESULTS: Neither attention bias nor baseline or recent trauma exposure predicted later anxiety. In contrast, attention bias toward threat and recent trauma exposure significantly predicted later trauma symptoms. There was evidence of symptom specificity such that attention bias toward threat significantly predicted hyperarousal and dissociation, but not avoidance or re-experiencing symptoms. Finally, moderation analyses indicated that the relationship between attention bias and trauma symptoms may differ according to children's experiences of probable abuse. CONCLUSIONS: Attention profiles and trauma exposure may increase the risk that young children will develop trauma symptoms. Individual differences in these attentional patterns and children's exposure history may impact outcomes among high-risk children with potential implications for intervention.© 2016 Association for Child and Adolescent Mental Health. Language: en

Fear and anxiety are conceptualized as responses to acute or potential threat, respectively. Adult twin studies found substantial interplay between genetic and environmental factors influencing fear disorders (phobias) and anxiety disorders. Research in children, however, has largely examined these factors independently. Thus, there exists a substantial knowledge gap regarding the underlying etiologic structure of these closely-related constructs during development. Symptom counts for five fear (criticism, the unknown, death, animal, medical) and four anxiety (generalized, panic, separation, social) dimensions were obtained for 373 twin pairs ages 9-14. Multivariate twin modeling was performed to elucidate the genetic and environmental influences distributed amongst these dimensions. The best fitting model contained one genetic, two familial environmental, and two unique environmental factors shared between fear and anxiety symptoms plus dimension-specific genetic and unique environmental factors. Although several environmental factors were shared between fear and anxiety dimensions, one latent factor accounted for genetic influences across both domains. While adult studies find somewhat distinct etiological differences between anxiety and phobic disorders, the current results suggest that their relative genetic and environmental influences are not as clearly demarcated in children. These etiological distinctions are more nuanced, likely contributing to the highly diffuse symptom patterns seen during development.

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low and medium but not high load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety-potentiated startle). The present work examines such threat-cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n-back task. Anxiety was induced using the threat of an aversive loud scream and measured via eyeblink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low and medium but not high load, and reaction times were faster during threat than safe conditions at high load but did not differ at other loads. Additionally, anxiety-potentiated startle was greater during low and medium than high load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging.

Attention to faces is a fundamental psychological process in humans, with atypical attention to faces noted across several clinical disorders. Although many clinical disorders onset in adolescence, there is a lack of well-validated stimulus sets containing adolescent faces available for experimental use. Further, the images comprising most available sets are not controlled for high- and low-level visual properties. Here, we present a cross-site validation of the National Institute of Mental Health Child Emotional Faces Picture Set (NIMH-ChEFS), comprised of 257 photographs of adolescent faces displaying angry, fearful, happy, sad, and neutral expressions. All of the direct facial images from the NIMH-ChEFS set were adjusted in terms of location of facial features and standardized for luminance, size, and smoothness. Although overall agreement between raters in this study and the original development-site raters was high (89.52%), this differed by group such that agreement was lower for adolescents relative to mental health professionals in the current study. These results suggest that future research using this face set or others of adolescent/child faces should base comparisons on similarly-aged validation data. Copyright © 2015 John Wiley & Sons, Ltd.

Behavioral inhibition (BI), a temperament characterized in early childhood by wariness and avoidance of novelty, is a risk factor for anxiety disorders. An enhanced startle response has been observed in adolescents characterized with BI in childhood, particularly when they also manifest concurrent symptoms of anxiety. However, no prior study has examined relations among BI, startle responsivity, and anxiety in a prospective manner. Data for the present study were from a longitudinal study of infant temperament. Maternal reports and observations of BI were assessed at ages 2 and 3. At age 7, participants completed a startle procedure, while electromyography was collected, where participants viewed different colors on a screen that were associated with either the delivery of an aversive stimulus (i.e., puff of air to the larynx; threat cue) or the absence of the aversive stimulus (i.e., safety cue). Parental reports of child anxiety were collected when children were 7 and 9 years of age. Results revealed that startle responses at age 7 moderated the relation between early BI and 9-year anxiety. These findings provide insight into one potential mechanism that may place behaviorally inhibited children at risk for anxiety.

Background Identifying anxiety disorders in preschool-age children represents an important clinical challenge. Observation is essential to clinical assessment and can help differentiate normative variation from clinically significant anxiety. Yet, most anxiety assessment methods for young children rely on parent-reports. The goal of this article is to present and preliminarily test the reliability and validity of a novel observational paradigm for assessing a range of fearful and anxious behaviors in young children, the Anxiety Dimensional Observation Schedule (Anx-DOS). Methods A diverse sample of 403 children, aged 3 to 6 years, and their mothers was studied. Reliability and validity in relation to parent reports (Preschool Age Psychiatric Assessment) and known risk factors, including indicators of behavioral inhibition (latency to touch novel objects) and attention bias to threat (in the dot-probe task) were investigated. Results The Anx-DOS demonstrated good inter-rater reliability and internal consistency. Evidence for convergent validity was demonstrated relative to mother-reported separation anxiety, social anxiety, phobic avoidance, trauma symptoms, and past service use. Finally, fearfulness was associated with observed latency and attention bias toward threat. Conclusions Findings support the Anx-DOS as a method for capturing early manifestations of fearfulness and anxiety in young children. Multimethod assessments incorporating standardized methods for assessing discrete, observable manifestations of anxiety may be beneficial for early identification and clinical intervention efforts.

BACKGROUND: Attention bias toward threat is associated with anxiety in older youth and adults and has been linked with violence exposure. Attention bias may moderate the relationship between violence exposure and anxiety in young children. Capitalizing on measurement advances, this study examines these relationships at a younger age than previously possible. METHODS: Young children (mean age 4.7, ±0.8) from a cross-sectional sample oversampled for violence exposure (N = 218) completed the dot-probe task to assess their attention biases. Observed fear/anxiety was characterized with a novel observational paradigm, the Anxiety Dimensional Observation Scale. Mother-reported symptoms were assessed with the Preschool Age Psychiatric Assessment and Trauma Symptom Checklist for Young Children. Violence exposure was characterized with dimensional scores reflecting probability of membership in two classes derived via latent class analysis from the Conflict Tactics Scales: Abuse and Harsh Parenting. RESULTS: Family violence predicted greater child anxiety and trauma symptoms. Attention bias moderated the relationship between violence and anxiety. CONCLUSIONS: Attention bias toward threat may strengthen the effects of family violence on the development of anxiety, with potentially cascading effects across childhood. Such associations maybe most readily detected when using observational measures of childhood anxiety. Language: en

Insecure attachment and behavioral inhibition (BI) increase risk for internalizing problems, but few longitudinal studies have examined their interaction in predicting adolescent anxiety. This study included 165 adolescents (ages 14-17 years) selected based on their reactivity to novelty at 4 months. Infant attachment was assessed with the Strange Situation. Multi-method BI assessments were conducted across childhood. Adolescents and their parents independently reported on anxiety. The interaction of attachment and BI significantly predicted adolescent anxiety symptoms, such that BI and anxiety were only associated among adolescents with histories of insecure attachment. Exploratory analyses revealed that this effect was driven by insecure-resistant attachment and that the association between BI and social anxiety was significant only for insecure males. Clinical implications are discussed.

Behavioral inhibition (BI) is a temperament associated with heightened vigilance and fear of novelty in early childhood, and social reticence and increased risk for anxiety problems later in development. However, not all behaviorally inhibited children develop signs of anxiety. One mechanism that might contribute to the variability in developmental trajectories is the recruitment of cognitive-control resources. The current study measured N2 activation, an ERP (event-related potential) associated with cognitive control, and modeled source-space activation (LORETA; Low Resolution Brain Electromagnetic Tomography) at 7 years of age while children performed a go/no-go task. Activation was estimated for the entire cortex and then exported for four regions of interest: ventromedial prefrontal cortex (VMPFC), ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dorsal ACC), and dorsal lateral prefrontal cortex (DLPFC). BI was measured in early childhood (ages 2 and 3 years). Anxiety problems and social reticence were measured at 7 years of age to ascertain stability of temperamental style. Results revealed that BI was associated with increased performance accuracy, longer reaction times, greater (more negative) N2 activation, and higher estimated dorsal ACC and DLPFC activation. Furthermore, early BI was only associated with social reticence at age 7 at higher (more negative) levels of N2 activation or higher estimated dorsal ACC or DLPFC activation. Results are discussed in the context of overcontrolled behavior contributing to social reticence and signs of anxiety in middle childhood.

Cognitive theories implicate information-processing biases in the etiology of anxiety disorders. Results of attention-bias studies in posttraumatic stress disorder (PTSD) have been inconsistent, suggesting biases towards and away from threat. Within-subject variability of attention biases in posttraumatic patients may be a useful marker for attentional control impairment and the development of posttrauma symptoms. This study reports 2 experiments investigating threat-related attention biases, mood and anxiety symptoms, and attention-bias variability following trauma. Experiment 1 included 3 groups in a cross-sectional design: (a) PTSD, (b) trauma-exposed without PTSD, and (c) healthy controls with no trauma or Axis I diagnoses. Greater attention-bias variability was found in the PTSD group compared to the other 2 groups (η(p)2=.23); attention-bias variability was significantly and positively correlated (r = .37) with PTSD symptoms. Experiment 2 evaluated combat-exposed and nonexposed soldiers before and during deployment. Attention-bias variability did not differentiate groups before deployment, but did differentiate groups during deployment (ηp2=.16); increased variability was observed in groups with acute posttraumatic stress symptoms and acute depression symptoms only. Attention-bias variability could be a useful marker for attentional impairment related to threat cues associated with mood and anxiety symptoms after trauma exposure.

Children with disinhibited eating behaviors rarely meet full criteria for DSM-defined eating disorders. Further, there is overwhelming agreement that the current system of psychiatric diagnosis does not adequately address the symptoms and problems with which patients of all ages present. With advances in neuroscience, questions have been raised regarding the degree to which measures of brain function can be used to address these problems in psychiatric nosology. The National Institute of Mental Health’s Research Domain Criteria (RDoC) program provides a guide for attempts to incorporate such measures into psychiatric classification by encouraging research on dimensions of observable behavior and neurobiology.1 In brief, RDoC is a framework that integrates advances in neuroscience and research in psychopathology. In order to facilitate basic and clinical research, fundamental components or “domains” were identified (See Table 1 for RDoC matrix). These domains isolated specific behaviors and their presumed underlying neural architecture, focusing on behaviors that manifest across multiple disorders currently classified as nosologically distinct. RDoC includes domains and associated brain systems tied to negative valence, positive valence, cognitive, social processes, and arousal/regulation that are broken down further into constructs.2 Units of analysis integrate genetic, neurobiological, physiological, behavioral, environmental, and experiential assessments. In line with its dimensional approach, RDoC aims to determine the full range of variation, from normal to abnormal, within a population of individuals with similar psychological symptoms. Unlike current nosology that is organized around clinical presentations, RDoC domains are structured based on brain-behavior relationships. Thus, RDoC is atheoretical in terms of its connections with existing theories of psychiatric classification. Table 1 Constructs to assess for a multi-modal study of early disinhibited eating and outcomes. RDoC is an exciting proposal both because it acknowledges vexing problems in current psychiatric classification and because it prioritizes research in neuroscience as a solution. Yet, moving from the current broad RDoC framework to tangible research questions and associated designs involves developing an approach that is both feasible and specific. A particular set of clinically important behaviors must be selected that are also tractable from the perspective of neuroscience. The current “Idea Worth Researching” applies the RDoC approach to research on disinhibited eating behavior, viewed from a developmental perspective. We propose a design highly specific in nature by determining selected units of analysis that may be linked based upon prior literature. Although our proposed study focuses solely on one domain, we conclude by broadly discussing how the other domains might fit into a more exhaustive, future RDoC study of disinhibited eating. We readily acknowledge that there are numerous other neural, genetic, physiological, and behavioral constructs that are relevant to disinhibited eating and the development of adverse outcomes. We also fully recognize that the constructs that we suggest for study may be relevant to multiple domains.

BACKGROUND: Psychopathic traits are associated with increases in antisocial behaviors such as aggression and are characterized by reduced empathy for others' distress. This suggests that psychopathic traits may also impair empathic pain sensitivity. However, whether psychopathic traits affect responses to the pain of others versus the self has not been previously assessed. METHOD: We used whole-brain functional magnetic resonance imaging to measure neural activation in 14 adolescents with oppositional defiant disorder or conduct disorder and psychopathic traits, as well as 21 healthy controls matched on age, gender, and intelligence. Activation in structures associated with empathic pain perception was assessed as adolescents viewed photographs of pain-inducing injuries. Adolescents imagined either that the body in each photograph was their own or that it belonged to another person. Behavioral and neuroimaging data were analyzed using random-effects analysis of variance. RESULTS: Youths with psychopathic traits showed reduced activity within regions associated with empathic pain as the depicted pain increased. These regions included rostral anterior cingulate cortex, ventral striatum (putamen), and amygdala. Reductions in amygdala activity particularly occurred when the injury was perceived as occurring to another. Empathic pain responses within both amygdala and rostral anterior cingulate cortex were negatively correlated with the severity of psychopathic traits as indexed by PCL:YV scores. CONCLUSIONS: Youths with psychopathic traits show less responsiveness in regions implicated in the affective response to another's pain as the perceived intensity of this pain increases. Moreover, this reduced responsiveness appears to predict symptom severity. Language: en

In humans, temperament plays an important role in socialization and personality. Some temperaments, such as behavioral inhibition are associated with an increased risk for psychopathology. Nonhuman primates can serve as a model for neurobiological and developmental contributions to emotional development and several recent studies have begun to investigate temperament in nonhuman primates. In rhesus monkeys, dominance rank is inherited from the mother and is associated with social and emotional tendencies that resemble differences in temperament. The current study assessed differences in temperament in infant rhesus monkeys as a function of maternal dominance rank. Temperament was assessed in 26 infants (13 males) from birth until 6 months of age with a battery that included Brazelton test, human intruder test, human intruder-startle, cortisol stress reactivity, and home cage observations of interactions with peers and the mother. Throughout testing, infants lived with their mothers and a small group of other monkeys in indoor/outdoor runs. Dominance rank of the mothers within each run was rated as either low/middle (N = 18, 9 male) or high/alpha (N = 8, 4 female). Infants of high-ranking mothers displayed more intruder-directed aggression and reduced startle potentiation in the human intruder tests. Dominant offspring also had reduced levels cortisol and startle across development and spent more time away from mothers in the interaction tests. These results suggest that dominance of the mother may be reflected in behavioral reactivity of infants early in life. These findings set up future studies, which may focus on contributing factors to both dominance and temperament such as genetics, rearing, and socialization. Such factors are likely to interact across development in meaningful ways. These results also suggest future human-based studies of a similar relationship may be warranted, although social dominance is clearly more complex in human than macaque societies.

It remains unclear whether BD presents in youth, as in adults, with only episodic mood symptoms or if chronic, severe non-episodic irritability is a developmental phenotype of BD. To study this question, Leibenluft et al. defined a new syndrome, severe mood dysregulation (SMD), to codify youth with chronic, non-episodic irritability. Although outcome and family history data (Brotman et al., 2007; Stringaris et al., 2010) differentiate SMD from `classic,' episodic BD, the underlying pathophysiology of these disorders is unclear. Functional magnetic resonance imaging (fMRI) studies comparing children with SMD and BD suggest that these two groups have both overlapping and distinct neural dysfunction (Adleman et al., 2011; Brotman et al., 2010; Deveney et al., 2012). However, no study compares neuroanatomy in children with SMD to those with BD and healthy volunteers (HV). In pediatric BD, research demonstrates structural abnormalities in many brain regions. Most studies report decreased cortical gray matter (GM) in BD vs. HV in a range of association cortex areas (Dickstein et al., 2005; Frazier et al., 2005; James et al., 2011; Wilke, Kowatch, DelBello, Mills, & Holland, 2004), and increased basal ganglia volumes in pediatric BD (DelBello, Zimmerman, Mills, Getz, & Strakowski, 2004; Liu et al., 2011; Wilke, et al., 2004). A recent meta-analysis in children and adults with BD reported that decreased prefrontal cortex and increased globus pallidus volumes were two of the most consistent findings (Arnone et al., 2009). Although there have been no structural MRI (sMRI) studies of SMD, the syndrome combines hyperarousal symptoms seen in attention-deficit/hyperactivity disorder (ADHD) with severe irritability (Leibenluft, 2011). In the ADHD neuroanatomical literature, the most replicated abnormality is decreased basal ganglia GM (Nakao, Radua, Rubia, & Mataix-Cols, 2011). However, since data suggest that SMD and non-irritable ADHD differ in neural activity (Brotman, et al., 2010), ADHD may differ from SMD neuroanatomically, and a study of children with SMD is warranted. While an emerging cross-sectional literature demonstrates structural brain abnormalities in adult and pediatric BD (Arnone, et al., 2009), the developmental trajectory of these abnormalities is unclear, and the trajectory is completely unstudied in SMD. Most previous longitudinal sMRI studies in pediatric BD include small samples, averaging around 10 patients (Blumberg et al., 2005; Gogtay et al., 2007; Kalmar et al., 2009). The most recent, and largest, study combined 58 late-adolescent and adult patients and reported greater GM volume increases over time in BD vs. HV in several regions, including superior temporal gyrus, basal ganglia, and medial temporal structures (Lisy et al., 2011). Given the limited literature in pediatric BD and the absence of research in SMD, we conducted a study comparing brain volume both cross-sectionally and longitudinally over two years in SMD, BD and HV. As previous fMRI and behavioral findings suggest that BD and SMD have both overlapping and distinct dysfunction, we hypothesized that we would find regions in which both SMD and BD differed from HV, and regions where the two patient groups differed from each other as well as HV. We expected group differences in association cortices and in basal ganglia, as such abnormalities have been reported in both BD and ADHD. However, given the lack of structural studies in SMD, we did not have specific hypotheses about the directionality of these findings. To explore both whole-brain and regional effects, as well as between- and within-group effects, we employed optimized voxel-based morphometry (VBM), a semi-automated method used to measure volume differences.

Frances (2009) concluded that: ‘it would be wisefor us all to accept that descriptive psychiatry is‘a tired old creature’ and that a paradigm shift isessential. Neither ICD-10 nor DSM-IV is fit forpurpose. Accordingly, the criterion that anyproposed changes must include justifications ismisleadingly one-sided. It is equally necessary tojustify why an outmoded system should beretained. … More well-thought-through work isgoing into revisions necessary for DSM-5 andICD-11 than was the case with any of the previ-ous changes. In particular, there has been muchmore effort to sort out where neuroscience standsin relation to classification and, in the case ofICD-11, also what are the public health impera-tives. It would be nai¨ve to suppose that neithereconomic issues nor bureaucratic rigidities andsilliness will affect distortion on sensible decisionmaking. Rutter (2011a)

Background Anxiety disorders are highly prevalent in children and adolescents, and are associated with aberrant emotion-related attention orienting and inhibitory control. While recent studies conducted with high-trait anxious adults have employed novel emotion-modified antisaccade tasks to examine the influence of emotional information on orienting and inhibition, similar studies have yet to be conducted in youths.

Background: Attention biases toward threat are often detected in individuals with anxiety disorders. Threat biases can be measured experimentally through dot-probe paradigms, in which individuals detect a probe following a stimulus pair including a threat. On these tasks, individuals with anxiety tend to detect probes that occur in a location previously occupied by a threat (i.e., congruent) faster than when opposite threats (i.e., incongruent). In pediatric anxiety disorders, dot-probe paradigms detect abnormal attention biases toward threat and abnormal ventrolateral prefrontal cortex (vlPFC) function. However, it remains unclear if this aberrant vlPFC activation occurs while subjects process threats (e.g., angry faces) or, alternatively, while they process and respond to probes. This magnetoencephalography (MEG) study was designed to answer this question. Methods: Adolescents with either generalized anxiety disorder (GAD, n = 17) or no psychiatric diagnosis (n = 25) performed a dot-probe task involving angry and neutral faces while MEG data were collected. Synthetic Aperture Magnetometry (SAM) beamformer technique was used to determine whether there were group differences in power ratios while subjects processed threats (i.e., angry vs. neutral faces) or when subjects responded to incongruent versus. congruent probes. Results: Group differences in vlPFC activation during the response period emerged with a 1-30 Hz frequency band. No group differences in vlPFC activation were detected in response to angry-face cues. Conclusions: In the dot-probe task, anxiety-related perturbations in vlPFC activation reflect abnormal attention control when responding to behaviorally relevant probes, but not to angry faces. Given that motor responses to these probes are used to calculate threat bias, this study provides insight into the pathophysiology reflected in this commonly used marker of anxiety. In addition, this finding may inform the development of novel anxiety-disorder treatments targeting the vlPFC to enhance attention control to task-relevant demands. Language: en

Background: Accurate identification of nonverbal emotional cues is essential to successful social interactions, yet most research is limited to emotional face expression labeling. Little research focuses on the processing of emotional prosody, or tone of verbal speech, in clinical populations. Methods: Using the Diagnostic Analysis of Nonverbal Accuracy, the current study examined whether youths with pediatric-onset bipolar disorder (BD) and/or those with chronic and severe irritability (i.e. the severe mood dysregulation phenotype) are impaired in their ability to identify the emotional prosody of a spoken sentence with neutral content. Results: Youths with severe mood dysregulation (n = 67) performed more poorly than healthy comparison children (n = 57), even when the sample was limited to unmedicated patients. Medicated BD youths (n = 52) exhibited impairment relative to healthy comparison children. No interactions between group and emotion were observed, suggesting that emotional prosody labeling problems may represent a general deficit in chronically irritable youths and in medicated youths with BD. Conclusion: In concert with previously documented facial emotion labeling deficits, difficulties ascertaining the correct emotional tone of a spoken sentence may contribute to emotion dysregulation in chronically irritable children, and possibly also in youths with BD.

With the emergence of new technologies, there has been an explosion of basic and clinical research on the affective and cognitive neuroscience of face processing and emotion perception. Adult emotional face stimuli are commonly used in these studies. For developmental research, there is a need for a validated set of child emotional faces. This paper describes the development of the National Institute of Mental Health Child Emotional Faces Picture Set (NIMH-ChEFS), a relatively large stimulus set with high quality, color images of the emotional faces of children. The set includes 482 photographs of fearful, angry, happy, sad and neutral child faces with two gaze conditions: direct and averted gaze. In this paper we describe the development of the NIMH-ChEFS and data on the set's validity based on ratings by 20 healthy adult raters. Agreement between the a priori emotion designation and the raters' labels was high and comparable with values reported for commonly used adult picture sets. Intensity, representativeness, and composite "goodness" ratings are also presented to guide researchers in their choice of specific stimuli for their studies. These data should give researchers confidence in the NIMH-ChEFS's validity for use in affective and social neuroscience research.

The modulation of the startle response (SR) by threatening stimuli (fear-potentiated startle; FPS), is a proposed endophenotype for disorders of the fearful-fearlessness spectrum. FPS has failed to show evidence of heritability, raising concerns. However, the metrics used to index FPS – and, importantly, other conditional phenotypes that are dependent on a baseline – may not be suitable for the approaches used in genetic epidemiology studies. Here we evaluated multiple metrics of FPS in a population-based sample of pre-adolescent twins (N = 569 from 320 twin pairs, M(age) = 11.4) who completed a fear-conditioning paradigm with airpuff-elicited SR on two occasions (~1 month apart). We applied univariate and multivariate biometric modeling to estimate the heritability of FPS using several proposed standardization procedures. This was extended with data simulations to evaluate biases in heritability estimates of FPS (and similar metrics) under various scenarios. Consistent with previous studies, results indicated moderate test-retest reliability (r = .59) and heritability of the overall SR (h(2) = 34%) but poor reliability and virtually no unique genetic influences on FPS when considering a raw or standardized differential score that removes baseline SR. Simulations demonstrated that the use of differential scores introduces bias in heritability estimates relative to jointly analyzing baseline SR and FPS in a multivariate model. However, strong dependency of FPS on baseline levels make unique genetic influences virtually impossible to detect regardless of methodology. These findings indicate that FPS and other conditional phenotypes may not be well-suited to serve as endophenotypes unless such co-dependency can be disentangled.

Objective Data documenting the functional impairment associated with the diagnosis of bipolar disorder (BD) in children and adolescents highlight the need for greater understanding of its pathophysiology. Toward that end, we demonstrated previously that BD youth have behavioral deficits on reversal learning tasks. On such tasks, participants must first acquire a stimulus/response relationship through trial-and-error learning, and then discern when the stimulus/reward relationship reverses. Here, we use event-related functional magnetic resonance imaging (fMRI) to elucidate neural correlates of reversal learning deficits in euthymic BD youth compared to typically developing controls.

This neuroimaging study examines the development of cognitive flexibility using the Change task in a sample of youths and adults. The Change task requires subjects to inhibit a prepotent response and substitute an alternative response, and the task incorporates an algorithm that adjusts task difficulty in response to subject performance. Data from both groups combined show a network of prefrontal and parietal areas that are active during the task. For adults vs. youths, a distributed network was more active for successful change trials versus go, baseline, or unsuccessful change trials. This network included areas involved in rule representation, retrieval (lateral PFC), and switching (medial PFC and parietal regions). These results are consistent with data from previous task-switching experiments and inform developmental understandings of cognitive flexibility.

This study examined relations among family environment, cortisol response, and behavior in the context of a randomized controlled trial with 92 children (M = 48 months) at risk for antisocial behavior. Previously, researchers reported an intervention effect on cortisol response in anticipation of a social challenge. The current study examined whether changes in cortisol response were related to later child aggression. Among lower warmth families, the intervention effect on aggression was largely mediated by the intervention effect on cortisol response. Although the intervention also resulted in significant benefits on child engaging behavior, cortisol response did not mediate this effect. These findings demonstrate meaningful associations between cortisol response and aggression among children at familial risk for antisocial behavior.

Background: Anxiety disorders are characterized by elevated, sustained responses to threat, that manifest as threat attention biases. Recent evidence also suggests exaggerated responses to incentives. How these characteristics influence cognitive control is under debate and is the focus of the present study. Methods: Twenty-five healthy adolescents and 25 adolescents meeting DSM-IV diagnostic criteria for an anxiety disorder were compared on a task of response inhibition. Inhibitory control was assayed with an antisaccade task that included both incentive (monetary reward) and incidental emotion (facial expression) cues presented prior to the execution of inhibitory behavior. Results: Inhibitory control was enhanced following exposure to threat cues (fear faces) only in adolescent patients, and following exposure to positive cues (happy faces) only in healthy adolescents. Results also revealed a robust performance improvement associated with monetary incentives. This incentive effect did not differ by group. No interaction between incentives and emotional cues was detected. Conclusions: These findings suggest that biased processing of threat in anxious adolescents affects inhibitory control, perhaps by raising arousal prior to behavioral performance. The absence of normalization of performance in anxious adolescents following exposure to positive emotional cues is a novel finding and will require additional exploration. Future studies will need to more specifically examine how perturbations in positive emotion processes contribute to the symptomatology and the pathogenesis of anxiety disorders.

Background: Individual differences in specific components of attention contribute to behavioral reactivity and regulation. Children with the temperament of behavioral inhibition (BI) provide a good context for considering the manner in which certain components of attention shape behavior. Infants and children characterized as behaviorally inhibited manifest signs of heightened orienting to novelty. The current study considers whether this attention profile moderates risk for clinical anxiety disorders among adolescents with a history of BI. Methods: Participants were assessed at multiple time points for BI, beginning in early childhood. At adolescence, event-related potentials (ERPs) were recorded during a three-stimulus auditory novelty oddball task, which employed frequent standard and infrequent deviant tones as well as a set of complex, novel sounds. Clinical diagnosis was carried out using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). P3 and mismatch negativity (MMN) components were examined at midline frontal, central, and parietal electrode sites. Results: Individuals who displayed high levels of BI during childhood and increased P3 amplitude to novelty in adolescence were more likely to have a history of anxiety disorders compared to behaviorally inhibited adolescents with lower P3 amplitudes. Groups did not differ on measures of MMN. Conclusions: Increased neural responses to novelty moderate risk for anxiety disorders amongst individuals with a history of BI.

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.

Objectives: Previous studies have indicated abnormalities in response flexibility in pediatric bipolar disorder (BD). Dysfunction in response flexibility may contribute to the pattern of behavioral and emotional dysregulation that is characteristic of BD, since depressed and manic patients respond inflexibly to emotional stimuli (i.e., anhedonia in the case of depression or inappropriate positive affect in the case of mania). The present study was undertaken to determine if neuronal responses differed between BD and control subjects on a simple motor response flexibility task. Methods: To elucidate the neural substrates mediating response flexibility in pediatric BD, we studied 25 youth with BD and 17 age-, gender- and IQ-matched controls (CON) as they performed the change task while undergoing event-related functional magnetic resonance imaging (fMRI). The change task is a new fMRI task that requires subjects to both inhibit and replace a prepotent motor response with another motor response after the initial response has been cued. Results: On correctly performed change trials relative to correctly performed go trials, BD patients generated significantly more activity in the left dorsolateral prefrontal cortex (DLPFC) and in the primary motor cortex than did healthy controls, even though performance levels did not differ across groups. Conclusions: These results indicate that functional deficits within the left DLPFC may mediate deficits in response flexibility in pediatric BD. This deficit may extend beyond the realm of motor control and also affect emotion regulation.

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 and SMD patients made more errors than ANX/MDD, ADHD/CD, or controls when labeling adult or child emotional expressions. BD and SMD patients did not differ in their emotion-labeling deficits. Conclusions: Face-emotion labeling deficits differentiate BD and SMD patients from patients with ANX/MDD or ADHD/CD and controls. The extent to which such deficits cause vs. result from emotional dysregulation requires further study.

Background: Maturation of prefrontal circuits during adolescence contributes to the development of cognitive processes such as decision-making. Recent theories suggest that these neural changes also play a role in the shift from generalized anxiety disorder (GAD) to depression that often occurs during this developmental period. Cognitive models of the development of GAD highlight the role of intolerance of uncertainty (IU), which can be characterized behaviorally by impairments in decision-making. The present study examines potential developmental differences in frontal regions associated with uncertain decision-making, and tests the impact of IU on these circuits. Methods: Twelve healthy adults (ages 19–36) and 12 healthy adolescents (ages 13–17) completed a decision-making task with conditions of varied uncertainty while fMRI scans were acquired. They also completed measures of worry and IU, and a questionnaire about their levels of anxiety and certainty during the task. Results: Combined group analyses demonstrated significant linear effects of uncertainty on activity within anterior cingulate cortex (ACC). Region of interest (ROI)-based analysis found a significant interaction of group and IU ratings in ACC. Increased IU was associated with robust linear increases in ACC activity only in adolescents. An ROI analysis of feedback-related processing found that adolescents demonstrated greater activation during incorrect trials relative to correct trials, while the adults showed no difference in neural activity associated with incorrect and correct feedback. Conclusions: This decision-making task was shown to be effective at eliciting uncertainty-related ACC activity in adults and adolescents. Further, IU impacts ACC activity in adolescents during uncertain decision-making, providing preliminary support for a developmental model of GAD.

Background: Studies in adults with major depressive disorder (MDD) document abnormalities in both memory and face-emotion processing. The current study used a novel face-memory task to test the hypothesis that adolescent MDD is associated with a deficit in memory for face-emotions. The study also examines the relationship between parental MDD and memory performance in offspring. Methods: Subjects were 152 offspring (ages 9‐19) of adults with either MDD, anxiety disorders, both MDD and anxiety, or no disorder. Parents and offspring were assessed for mental disorders. Collection of face-memory data was blind to offspring and parent diagnosis. A computerized task was developed that required rating of facial photographs depicting ‘happy,’ ‘fearful,’ or ‘angry’ emotions followed by a memory recall test. Recall accuracy was examined as a function of face-emotion type. Results: Age and gender independently predicted memory, with better recall in older and female subjects. Controlling for age and gender, offspring with a history of MDD (n ¼ 19) demonstrated significant deficits in memory selectively for fearful faces, but not happy or angry faces. Parental MDD was not associated with face-memory accuracy. Discussion: This study found an association between MDD in childhood or adolescence and perturbed encoding of fearful faces. MDD in young individuals may predispose to subtle anomalies in a neural circuit encompassing the amygdala, a brain region implicated in the processing of fearful facial expressions. These findings suggest that brain imaging studies using similar face-emotion paradigms should test whether deficits in processing of fearful faces relate to amygdala dysfunction in children and adolescents with MDD. Keywords: Face processing, adolescence, depression, cognitive neuroscience.

Background: Prior studies document strong interactions between emotional and mnemonic processes. These interactions have been shown to vary across development and psychopathology, particularly mood and anxiety disorders. Methods: The present study used functional neuroimaging to assess the degree to which adolescents and adults differ in patterns of neuronal engagement during implicit encoding of affective stimuli. Subjects underwent rapid event-related fMRI while viewing faces with angry, fearful, happy, and neutral expressions. A surprise post-scan memory test was administered. Results: Consistent with previous findings, both adolescents and adults displayed engagement of left ventrolateral prefrontal cortex when viewing subsequently recognized stimuli. Age differences emerged in patterns of neuronal activation associated with subsequent recognition of specific face-emotion types. Relative to adults, adolescents displayed more activity in the anterior cingulate when viewing subsequently remembered angry faces, and more activity in the right temporal pole when viewing subsequently remembered fear faces. Conversely, adults displayed more activity in the subgenual anterior cingulate when viewing subsequently remembered happy faces and more activity in the right posterior hippocampus when viewing subsequently remembered neutral faces. These age-related differences emerged in the absence of differences in behavioral performance. Conclusions: These findings document developmental differences in the degree to which engagement of affective circuitry contributes to memory formation.

Findings from the Watamura, Donzella, Alwin, and Gunnar (this issue) study support the growing recognition of the importance of context on physiology and affective and behavioral regulation early in human development. This discussion focuses on the role of context and development on hypothalamic-pituitary-adrenal (HPA) axis regulation in young children. Discussed in this article are the Watamura et al. findings with regard to relevant animal studies, extension of these observations to samples of children at elevated risk for psychopathology, and experimental prevention studies with young children. It is contended that environmental factors operating at key points in development may shape affective and behavioral regulation as well as HPA axis function in children, much as environmental factors have been shown to shape HPA axis regulation in animals.