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OBJECTIVE: Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder. Studies of the neural circuitry engaged during failed motor inhibition in pediatric bipolar disorder may increase our understanding of the pathophysiology of the illness. The authors tested the hypothesis that children with bipolar disorder and comparison subjects would differ in ventral prefrontal cortex, striatal, and anterior cingulate activation during unsuccessful motor inhibition. They also compared activation in medicated versus unmedicated children with bipolar disorder and in children with bipolar disorder and attention deficit hyperactivity disorder (ADHD) versus those with bipolar disorder without ADHD. METHOD: The authors conducted an event-related functional magnetic resonance imaging study comparing neural activation in children with bipolar disorder and healthy comparison subjects while they performed a motor inhibition task. The study group included 26 children with bipolar disorder (13 unmedicated and 15 with ADHD) and 17 comparison subjects matched by age, gender, and IQ. RESULTS: On failed inhibitory trials, comparison subjects showed greater bilateral striatal and right ventral prefrontal cortex activation than did patients. These deficits were present in unmedicated patients, but the role of ADHD in mediating them was unclear. CONCLUSIONS: In relation to comparison subjects, children with bipolar disorder may have deficits in their ability to engage striatal structures and the right ventral prefrontal cortex during unsuccessful inhibition. Further research should ascertain the contribution of ADHD to these deficits and the role that such deficits may play in the emotional and behavioral dysregulation characteristic of bipolar disorder. [ABSTRACT FROM AUTHOR]

Background. Many changes in social behavior take place during adolescence. Sexuality and romantic interests emerge during this time, and adolescents spend more time with peers and less time with parents and family. While such changes in social behavior have been well documented in the literature, relatively few neurophysiological explanations for these behavioral changes have been presented.Method. In this article we selectively review studies documenting (a) the neuronal circuits that are dedicated to the processing of social information; (b) the changes in social behavior that take place during adolescence; (c) developmental alterations in the adolescent brain; and (d) links between the emergence of mood and anxiety disorders in adolescence and changes in brain physiology occurring at that time.Results. The convergence of evidence from this review indicates a relationship between development of brain physiology and developmental changes in social behavior. Specifically, the surge of gonadal steroids at puberty induces changes within the limbic system that alters the emotional attributions applied to social stimuli while the gradual maturation of the prefrontal cortex enables increasingly complex and controlled responses to social information.Conclusions. Observed alterations in adolescent social behavior reflect developmental changes in the brain social information processing network. We further speculate that dysregulation of the social information processing network in this critical period may contribute to the onset of mood and anxiety disorders during adolescence. [ABSTRACT FROM AUTHOR]

What are the effects of sertraline in children and adolescents with major depressive disorder (MDD)?METHODS:Design: Two randomised controlled trials.Allocation: Concealed.Blinding: Double blinded (clinicians, patients).Follow up period: 10 weeks.Setting: Two identically designed trials run concurrently in 53 hospital, general practice and academic centres in USA, India, Canada, Costa Rica, and Mexico; enrolment December 1999 to May 2001.Patients: 376 children and adolescents aged 6 to 17 years with a current episode of MDD (DSM-IV criteria) lasting at least 6 weeks, and scoring at least 45 on the Children's Depression Rating Scale-Revised (CDRS-R) and at least 4 on the Clinical Global Impression Scale of Severity of Illness (CGI-S) during 3 visits within a 2 week screening period. Exclusions: attention deficit/hyperactivity disorder, conduct disorder, obsessive compulsive disorder, panic disorder, or psychotic features; history of bipolar, psychotic, or autistic spectrum disorders; suicidal or homicidal risk; abnormal ECG, lab tests, vital signs, or body weight; pregnancy; previous enrolment in sertraline trial; contraindication to SSRIs and history of non-responsiveness to SSRls. Participants needed to be free of psychotropic medication for at least 2 weeks (4 weeks for fluoxetine). Diphenhydramine or chloral hydrate were permitted as sleeping aids. Participants could continue with ongoing psychotherapy, but not cognitive behaviour therapy.Intervention: 25mg/day sertraline for 3 days, then 50mg/day until the end of the second week; dosage was then titrated up to a maximum of 200mg/day for optimum clinical response (n=189); or placebo (n=187).Outcomes: Severity of depressive symptoms (rated using the 17 item clinician rated CDRS-R (scores range from 17=least severe to 1 13=most severe), response (responders defined as having at least a 40% decrease in the adjusted CDRS-R total score) and adverse effects.Patient follow up: Efficacy analysis 97%; safety analysis 99%.MAIN RESULTS:Sertraline significantly improved depressive symptoms compared with placebo over 10 weeks (mean change in CDRS-R score: -22.8 with sertraline v -20.2 with placebo; p=0.007; analysis not by intention to treat). 69% of the sertraline group responded, compared with 59% of the placebo group (p=0.05). More participants in the sertraline group withdrew due to adverse effects than in the placebo group (17/189 (9%) with sertraline v 5/187 (3%) in the placebo group; p = 0.14 (Fisher's exact, calculated from results as significance not stated in paper)). Adverse effects occurring in at least 5% of the sertraline group, and with an incidence of at least twice that of the placebo group were: insomnia, diarrhoea, anorexia, vomiting, agitation, urinary incontinence, and purpura.CONCLUSION:Sertraline is an effective and safe short term treatment for children and adolescents with MDD. [ABSTRACT FROM AUTHOR]

Reducing the amount of donor skin needed for definitive wound closure can improve outcomes in patients with severe burns. This Delphi Consensus Panel (DCP) aimed to achieve expert consensus on the percentage reduction in donor skin for autograft that constitutes a clinically meaningful benefit. A two-round DCP of fifteen US burn surgeons was conducted via a web-based survey platform. Fourteen panelists (93.3%) completed both rounds. In Round 2, consensus, defined as ≥70% agreement, was achieved for five of the seven consensus statements. All panelists agreed that a clinically meaningful reduction in the amount of donor skin required would facilitate wound management and decrease donor site morbidity experienced by patients. Furthermore, based on three treatment scenarios, consensus was achieved for a clinically meaningful reduction in the amount of donor skin required for autograft for the adult population in deep partial-thickness and full-thickness burns. Findings from this DCP indicate that an innovative cellular and/or tissue product that would reduce the needed amount of donor skin, by the identified thresholds, has the potential to improve the outcomes for patients with severe burn injuries in a meaningful way., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

This study examined patterns of behavioral and emotional responses to conflict and cooperation in adolescents with anxiety/mood disorders and healthy peers. We compared performance on and emotional responses to the Prisoner's Dilemma (PD) game, an economic exchange task involving conflict and cooperation, between adolescents with anxiety/depressive disorders (A/D) (N=21) and healthy comparisons (n = 29). Participants were deceived to believe their co-player (a pre-programmed computer algorithm) was another study participant. A/D adolescents differed significantly from comparisons in patterns of play and emotional response to the game. Specifically, A/D participants responded more cooperatively to cooperative overtures from their co-players; A/D girls also reported more anger toward co-players than did comparison girls. Our findings indicate that A/D adolescents, particularly females, respond distinctively to stressful social interchanges. These findings offer a first step toward elucidating the mechanisms underlying social impairment in youth with internalizing disorders.

Behavioral inhibition (BI) is a risk factor for anxiety disorders. While the two constructs bear behavioral similarities, previous work has not extended these parallels to the neural level. This study examined amygdala reactivity during a task previously used with clinically anxious adolescents. Adolescents were selected for enduring patterns of BI or non-inhibition (BN). We examined amygdala response to evocative emotion faces in BI (N=10, mean 12.8 years) and BN (N=17, mean 12.5 years) adolescents while systematically manipulating attention. Analyses focused on amygdala response during subjective ratings of internal fear (constrained attention) and passive viewing (unconstrained attention) during the presentation of emotion faces (Happy, Angry, Fearful, and Neutral). BI adolescents, relative to BN adolescents, showed exaggerated amygdala response during subjective fear ratings and deactivation during passive viewing, across all emotion faces. In addition, the BI group showed an abnormally high amygdala response to a task condition marked by novelty and uncertainty (i.e., rating fear state to a Happy face). Perturbations in amygdala function are evident in adolescents temperamentally at risk for anxiety. Attention state alters the underlying pattern of neural processing, potentially mediating the observed behavioral patterns across development. BI adolescents also show a heightened sensitivity to novelty and uncertainty, which has been linked to anxiety. These patterns of reactivity may help sustain early temperamental biases over time and contribute to the observed relation between BI and anxiety.

Objective: Clinicians and researchers debate whether children with chronic, nonepisodic irritability should receive the diagnosis of bipolar disorder (BD). To address this debate, we evaluated cognitive flexibility, or the ability to adapt to changing contingencies, in three groups of children: narrow-phenotype BD (NP-BD; full-duration manic episodes of elevated/expansive mood; N = 50; 13.1 +/- 2.9 years), severe mood dysregulation (SMD; chronic, nonepisodic irritability; N = 44; 12.2 +/- 2.1 years), and healthy controls (N = 43; 13.6 +/- 2.4 years). Cognitive flexibility is relevant to symptoms of BD involving dysfunctional reward systems (e.g., excessive goal-directed activity and pleasure-seeking in mania; anhedonia in depression)., Method: We studied simple and compound reversal stages of the intra-/extradimensional shift task and change task that involves inhibiting a prepotent response and substituting a novel response., Results: On the simple reversal, NP-BD youths were significantly more impaired than both the SMD group and controls. On the compound reversal, NP-BD and SMD youths performed worse than controls. On the change task, NP-BD youths were slower to adapt than SMD subjects., Conclusions: Phenotypic differences in cognitive flexibility may reflect different brain/behavior mechanisms in these two patient populations.

Introduction: A growing number of studies have found evidence that anxiety and depressive disorders are associated with atypical amygdala hyperactivation, which decreases with effective treatment. Interest has emerged in this phenomenon as a possible biological marker for individuals who are likely to benefit from tailored treatment approaches., Objective: The present study was designed to examine relationships between pretreatment amygdala activity and treatment response in a sample of anxious children and adolescents., Materials and Methods: Participants, who were diagnosed predominantly with generalized anxiety disorder (GAD), underwent functional magnetic resonance imaging (fMRI) scanning before treatment with fluoxetine or cognitive behavioral therapy (CBT)., Results: Results indicated significant negative associations between degree of left amygdala activation and measures of posttreatment symptom improvement in the group, as a whole., Discussion: Taken together with research on associations between adult amygdala activation and treatment response, these findings suggest that patients whose pretreatment amygdala activity is the strongest may be particularly likely to respond well to such widely used treatments as selective serotonin reuptake inhibitor (SSRI) medications and CBT.

Context: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues., Objective: To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents., Design: Case-control study., Setting: Government clinical research institute., Participants: Fifteen adolescents with generalized anxiety disorder and 20 controls., Main Outcome Measures: Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention., Results: While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex., Conclusions: This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.

Background: Although major depressive disorder (MDD) represents one of the most serious psychiatric problems afflicting adolescents, efforts to understand the neural circuitry of adolescent MDD have lagged behind those of adult MDD. This study tests the hypothesis that adolescent MDD is associated with abnormal amygdala activity during evocative-face viewing., Methods: Using functional magnetic resonance imaging (fMRI), between-group differences among MDD (n = 10), anxious (n = 11), and non-psychiatric comparisons (n = 23) were examined during successful vs. unsuccessful face encoding, with encoding success measured post-scan., Results: Compared to healthy adolescents, MDD patients exhibited poorer memory for faces. fMRI analyses accounted for this performance difference through event-related methods. In an analysis comparing successful vs. unsuccessful face encoding, MDD patients exhibited greater left amygdala activation relative to healthy and anxious youth., Conclusions: Given prior findings among adults, this study suggests that adolescent and adult MDD may involve similar underlying abnormalities in amygdala functioning.

Reflecting a paradigm shift in clinical neuroscience, many chronic psychiatric illnesses are now hypothesized to result from perturbed neural development. However, most work in this area focuses on schizophrenia. Here, we extend this paradigm to pediatric bipolar disorder (BD), thus demonstrating traction in the developmental psychobiology perspective. To study amygdala dysfunction, we examined neural mechanisms mediating face processing in 22 youths (mean age 14.21 +/- 3.11 yr) with BD and 21 controls of comparable age, gender, and IQ. Event-related functional MRI compared neural activation when attention was directed to emotional aspects of faces (hostility, subjects' fearfulness) vs. nonemotional aspects (nose width). Compared with controls, patients perceived greater hostility in neutral faces and reported more fear when viewing them. Also, compared with controls, patients had greater activation in the left amygdala, accumbens, putamen, and ventral prefrontal cortex when rating face hostility, and greater activation in the left amygdala and bilateral accumbens when rating their fear of the face. There were no between-group behavioral or neural differences in the nonemotional conditions. Results implicate deficient emotion-attention interactions in the pathophysiology of BD in youth and suggest that developmental psychobiology approaches to chronic mental illness have broad applicability.

Objective: While adolescent anxiety disorders represent prevalent, debilitating conditions, few studies have explored their brain physiology. Using event-related functional magnetic resonance imaging (fMRI) and a behavioral measure of attention to angry faces, the authors evaluated differences in response between healthy adolescents and adolescents with generalized anxiety disorder., Method: In the primary trials of interest, 18 adolescents with generalized anxiety disorder and 15 comparison subjects of equivalent age/gender/IQ viewed angry/neutral face pairs during fMRI acquisition. Following the presentation of each face pair, subjects pressed a button to indicate whether a subsequent asterisk appeared on the same (congruent) or opposite (incongruent) side as the angry face. Reaction time differences between congruent and incongruent face trials provided a measure of attention bias to angry faces., Results: Relative to the comparison subjects, patients with generalized anxiety disorder manifested greater right ventrolateral prefrontal cortex activation to trials containing angry faces. Patients with generalized anxiety disorder also showed greater attention bias away from angry faces. Ventrolateral prefrontal cortex activation differences remained evident when differences in attention bias were covaried. Finally, in an examination among patients of the association between degree of anxiety and brain activation, the authors found that as ventrolateral prefrontal cortex activation increased, severity of anxiety symptoms diminished., Conclusions: Adolescents with generalized anxiety disorder show greater right ventrolateral prefrontal cortex activation and attentional bias away from angry faces than healthy adolescents. Among patients, increased ventrolateral prefrontal cortex activation is associated with less severe anxiety, suggesting that this activation may serve as a compensatory response.

Fear conditioning represents the process by which a neutral stimulus comes to evoke fear following its repeated pairing with an aversive stimulus. Although fear conditioning has long been considered a central pathogenic mechanism in anxiety disorders, studies employing lab-based conditioning paradigms provide inconsistent support for this idea. A quantitative review of 20 such studies, representing fear-learning scores for 453 anxiety patients and 455 healthy controls, was conducted to verify the aggregated result of this literature and to assess the moderating influences of study characteristics. Results point to modest increases in both acquisition of fear learning and conditioned responding during extinction among anxiety patients. Importantly, these patient-control differences are not apparent when looking at discrimination studies alone and primarily emerge from studies employing simple, single-cue paradigms where only danger cues are presented and no inhibition of fear to safety cues is required.

Objective: Little is known about neuropsychological and social-cognitive function in patients with pediatric bipolar disorder. Identification of specific deficits and strengths that characterize pediatric bipolar disorder would facilitate advances in diagnosis, treatment, and research on pathophysiology. The purpose of this study was to test the hypothesis that youths with bipolar disorder would perform more poorly than matched healthy comparison subjects on measures of social cognition, motor inhibition, and response flexibility., Method: Forty outpatients with pediatric bipolar disorder and 22 comparison subjects (no differences in age, gender, and IQ) completed measures of social cognition (the pragmatic judgment subtest of the Comprehensive Assessment of Spoken Language, facial expression recognition subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale, the oral expression subtest of the Test of Language Competence), inhibition and response flexibility (stop and stop-change tasks), and motor inhibition (continuous performance tasks)., Results: Pediatric bipolar disorder patients performed more poorly than comparison subjects on social-cognitive measures (pragmatic judgment of language, facial expression recognition) and on a task requiring response flexibility. These deficits were present in euthymic patients. Differences between patients and comparison subjects could not be attributed to comorbid attention deficit hyperactivity disorder., Conclusions: Findings of impaired social cognition and response flexibility in youths with pediatric bipolar disorder suggest continuity between pediatric bipolar disorder and adult bipolar disorder. These findings provide a foundation for neurocognitive research designed to identify the neural mechanisms underlying these deficits.

Introduction: Anxiety disorders in adults involve aberrant processing of emotional information that is hypothesized to reflect perturbations in the amygdala. This study examines the relationship between face-emotion recognition and anxiety in a sample of children and adolescents participating in a brain-imaging study of amygdala structure and function., Methods: This study recruited 15 children and adolescents with ongoing anxiety disorders and 11 psychiatrically healthy comparisons group-matched on age, gender, and IQ. Face-emotion recognition was assessed using the Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA)., Results: Children and adolescents with anxiety disorders exhibited significantly poorer performance on the face-emotion recognition task compared to healthy controls (z = 2.2; p < 0.05). This difference was found only for expressions posed by adults but not children., Discussion: Reduced accuracy on a face-emotion recognition test is consistent with perturbed amygdala function in pediatric anxiety disorders., Conclusion: As this study was conducted in a sample undergoing a neuroimaging investigation of amygdala integrity, future analyses will examine associations among amygdala function, clinical anxiety, and face-recognition abilities.

Adolescents' propensity for risk-taking and reward-seeking behaviors suggests a heightened sensitivity for reward, reflected by greater feedback-related activity changes in reward circuitry (e.g., nucleus accumbens), and/or a lower sensitivity to potential harm reflected by weaker feedback-related activity changes in avoidance circuitry (e.g., amygdala) relative to adults. Responses of nucleus accumbens and amygdala to valenced outcomes (reward receipt and reward omission) were assayed using an event-related functional magnetic resonance imaging procedure paired with a monetary reward task in 14 adults and 16 adolescents. Bilateral amygdala and nucleus accumbens showed significantly greater activation when winning than when failing to win in both groups. Group comparisons revealed stronger activation of left nucleus accumbens by adolescents, and of left amygdala by adults. When examining responses to reward receipts and to reward omissions separately, the most robust group difference was within the amygdala during reward omission. The reduction of the fMRI BOLD signal in the amygdala in response to reward omission was larger for adults than for adolescents. Correlations showed a close link between negative emotion and amygdala decreased BOLD signal in adults, and between positive emotion and nucleus accumbens activation in adolescents. Overall, these findings support the notion that the signal differences between positive and negative outcomes involve the nucleus accumbens more in adolescents than in adults, and the amygdala more in adults than in adolescents. These developmental differences, if replicated, may have important implications for the development of early-onset disorders of emotion and motivation.

Objective: To test the hypothesis that patients with pediatric bipolar disorder (PBPD) would demonstrate impairment relative to diagnosis-free controls of comparable age, gender, and IQ on measures of memory functioning., Method: The authors administered a battery of verbal and visuospatial memory tests to 35 outpatients with PBPD and 20 healthy controls who participated as volunteers in this study. Groups did not differ on age, gender, or IQ., Results: Consistent with findings in adults with BPD, patients with PBPD performed more poorly than controls on measures of verbal learning/memory and delayed facial recognition memory. Impaired memory was particularly evident in patients with comorbid PBPD/attention-deficit/hyperactivity disorder or acute mood symptoms., Conclusions: These findings suggest that deficits in verbal learning and memory, as well as some aspects of visuospatial memory, characterize patients with narrow phenotype PBPD. Further research is needed, however, to clarify the roles of comorbid attention-deficit/hyperactivity disorder and acute mood state in the emergence of these deficits. Given the apparent continuity in memory dysfunction between adult BPD and narrow phenotype PBPD, research aimed at elucidating underlying neural mechanisms for this set of deficits is warranted.

Biased attention to threat represents a key feature of anxiety disorders. This bias is altered by therapeutic or stressful experiences, suggesting that the bias is plastic. Charting on-line behavioral and neurophysiological changes in attention bias may generate insights on the nature of such plasticity. We used an attention-orientation task with threat cues to examine how healthy individuals alter their response over time to such cues. In Experiments 1 through 3, we established that healthy individuals demonstrate an increased attention bias away from threat over time. For Experiment 3, we used functional magnetic resonance imaging to determine the neural bases for this phenomenon. Gradually increasing attention bias away from threat is associated with increased activation in the occipitotemporal cortex. Examination of plasticity of attention bias with individuals at risk for anxiety disorders may reveal how threatening stimuli come to be categorized differently in this population over time.

Background: Females appear to be more sensitive and responsive to social cues, including threat signals, than are males. Recent theoretical models suggest that developmental changes in brain functioning play important roles in the emergence of such gender differences., Methods: We used functional magnetic resonance imaging to examine developmental and gender differences in activation of neural structures thought to mediate attention to emotional faces depicting varying degrees of threat. Analyses focused on the orbitofrontal cortex, amygdala, and anterior cingulate cortex during the evaluation of threat conveyed by faces. Healthy adolescents (n = 17; 53% male) and adults (n = 17; 53% male) were scanned while they rated how threatening pictures of neutral and emotional (angry, fearful, or happy) faces appeared., Results: Results indicate significant interactions among age, gender, and face type for activation during explicit threat monitoring. In particular, adult women activated orbitofrontal cortex and amygdala selectively to unambiguous threat (angry) cues, while adult men showed a less discriminating pattern of activation. No gender differences were evident for adolescents, who as a group resembled adult males., Conclusions: These findings suggest that there are gender differences in patterns of neural responses to emotional faces that are not fully apparent until adulthood.

We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA 11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation.

Background: Growing awareness of childhood bipolar disorder necessitates further cognitive neuroscience research to determine unique developmental differences between pediatric and adult onset bipolar disorder. We sought to examine whether neuropsychological function in children with bipolar disorder resembles that in adults with the illness and to extend our knowledge about cognitive function in pediatric bipolar disorder., Methods: We administered a computerized neuropsychological test battery known as the Cambridge Neuropsychological Test Automated Battery to a sample of 21 children and adolescents with bipolar disorder and compared them with 21 age- and gender-matched controls., Results: In comparison to controls, children with bipolar disorder were impaired on measures of attentional set-shifting and visuospatial memory. Post hoc analyses in pediatric bipolar disorder subjects did not show significant associations between neuropsychological performance and manic symptomatology or attention-deficit/hyperactivity disorder comorbidity., Conclusions: Cambridge Neuropsychological Test Automated Battery data presented here in pediatric bipolar disorder fit well within the broader framework of known neurocognitive deficits in adult bipolar disorder. Our pediatric bipolar disorder subjects demonstrated selective deficiencies in attentional set-shifting and visuospatial memory. Our work suggests altered ventrolateral prefrontal cortex function, especially when linked to other lesion and neuroimaging studies.

Little is understood about the brain basis of anxiety, particularly among youth. However, threat paradigms with animals are delineating the relationship between anxietylike behaviors and brain function. We adapted a threat paradigm for adolescents using functional magnetic resonance imaging. The aim was to examine amygdala activation to fear. The threat was an aversive air blast directed to the larynx. Participants were explicitly informed that they might receive the air blast when viewing one stimulus (threat condition) and would not receive the blast when viewing the other stimulus (safe condition). Participants provided fear ratings immediately after each trial. Based on the relatively mild nature of the air blast, we expected participants to report varying degrees of fear. Those who reported increased fear showed right amygdala activation during the threat condition and left amygdala activation in the safe condition. These procedures offer a promising tool for studying youth with anxiety disorders.

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.

Selective attention, particularly during the processing of emotionally evocative events, is a crucial component of adolescent development. We used functional magnetic resonance imagining (fMRI) with adolescents and adults to examine developmental differences in activation in a paradigm that involved selective attention during the viewing of emotionally engaging face stimuli. We evaluated developmental differences in neural activation for three comparisons: (1) directing attention to subjective responses to fearful facial expressions relative to directing attention to a nonemotional aspect (nose width) of fearful faces, (2) viewing fearful relative to neutral faces while attending to a nonemotional aspect of the face, and (3) viewing fearful relative to neutral faces while attention was unconstrained (passive viewing). The comparison of activation across attention tasks revealed greater activation in the orbital frontal cortex in adults than in adolescents. Conversely, when subjects attended to a nonemotional feature, fearful relative to neutral faces influenced activation in the anterior cingulate more in adolescents than in adults. When attention was unconstrained, adolescents relative to adults showed greater activation in the anterior cingulate, bilateral orbitofrontal cortex, and right amygdala in response to the fearful relative to neutral faces. These findings suggest that adults show greater modulation of activity in relevant brain structures based on attentional demands, whereas adolescents exhibit greater modulation based on emotional content.

Objective: The authors examined facial expression recognition in adolescents with mood and anxiety disorders., Method: Standard facial emotion identification tests were given to youth with bipolar disorder (N=11) or DSM-IV anxiety disorders (N=10) and a group of healthy comparison subjects (N=25)., Results: Relative to the anxiety disorder and healthy comparison groups, the subjects with bipolar disorder made more emotion recognition errors when presented with faces of children. Unlike the anxious and comparison subjects, bipolar disorder youth were prone to misidentify faces as angry. No differences in emotion recognition errors were seen when the adolescents were presented with adult faces., Conclusions: A bias to misinterpret the facial expressions of peers as angry may characterize youth with bipolar disorder but not youth with anxiety disorders. This bias may relate to social impairment in youth with bipolar disorder.

This study was designed to explore the role of perceived parenting behavior in the relationship between parent and offspring anxiety disorders in a high-risk sample of adolescents. We examined the relationship between parental and child anxiety disorders and tested whether perceived parenting behavior acted as a mediator between these variables. Analyses were performed on a high-risk sample of 816 fifteen-year-olds drawn from a birth cohort in Queensland, Australia. Parental depression and income were covaried. Maternal anxiety disorder significantly predicted the presence of anxiety disorders in children; the association between paternal anxiety disorder and child anxiety disorder was not significant. There was no evidence that perceived parenting played a mediating role in the association between mother and child anxiety disorders. These results replicate earlier studies' findings of elevated rates of anxiety disorders among the offspring of anxious parents, but only when the child's mother is the anxious parent.

Quantitative and qualitative reviews of the literature on sex differences in facial expression processing (FEP) have yielded conflicting findings regarding children. This study was designed to review quantitatively the literature on sex differences in FEP from infancy through adolescence and to evaluate consistency between the course of FEP development and predictions derived from preliminary theoretical models. Results, which indicate a female advantage at FEP, are consistent with predictions derived from an integrated neurobehavioral/social constructivist model. These findings suggest a need for research examining both neurological maturation and socialization as important factors in the development of sex differences in FEP and related skills. Possible directions for future study are discussed, with emphasis on the need to integrate the infant literature with research focused on older children and adults.

The 18q- syndrome is one of the commonest deletion syndromes. Clinical characteristics are variable but may include: hypotonia, tapered digits, "carp-like" mouth, mental retardation, and hearing impairment. Growth failure (GF; both weight and height < 3%) was reported in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 5 18q- syndrome patients, 3 of whom had growth failure (< 3% weight and height); the remaining 2 had normal growth parameters. Laboratory evaluation of growth included measurement of IGF-1, IGFBP-3, bone ages and GH response to pituitary provocative agents. Three patients failed to produced adequate GH following stimulation testing. Of 3 patients with inadequate GH production, 1 had normal growth (above 3%). Only 1 of 5 patients had normal GH production and normal growth parameters. Our findings to date suggest that GH deficiency is common in individuals with the 18q- syndrome. The pathogenesis of this finding is unknown. We postulate that a gene(s) on 18q is involved in GH production.