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Objective: A preliminary investigation of the impact of a serotonergic agent (fluoxetine) on symptom profile and neural response in youths with disruptive behavior disorders (DBDs) and a history of trauma exposure. Methods: There were three participant groups: (i) Youths with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 11); (ii) A matched group of youths with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 10); and (iii) Typically developing youths (n = 18). All participants conducted an expression processing functional magnetic resonance imaging task twice, 8 weeks apart: (pretreatment and post-treatment for youths with DBDs). Results: Youths with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) as a function of fearful expression intensity, significantly decreased amygdala response and increased recruitment of regions implicated in top-down attention control (insula cortex, inferior parietal lobule, and postcentral gyrus) and emotional regulation (ventromedial prefrontal cortex [vmPFC]); and (iii) correlation between DBD/irritability symptom improvement and increased activation of top-down attention control areas (inferior parietal lobule, insula cortex, and postcentral gyrus) and an emotion regulation area (vmPFC). Conclusions: This study provides preliminary evidence that a serotonergic agent (fluoxetine) can reduce disruptive behavior and mood symptoms in youths with DBDs and trauma exposure and that this may be mediated by enhanced activation of top-down attention control and emotion regulation areas (inferior parietal lobule, insula cortex, and vmPFC).

Objectives: Temporal reward discounting impulsivity (TDI) reflects a propensity to choose smaller immediate rather than larger delayed rewards relative to age/IQ-matched peers. Previous work with adults has linked TDI to an increased risk for antisocial behavior but also psychopathology in general. However, little work has examined TDI in adolescents with conduct disorder (CD), or considered whether TDI might be associated dimensionally with traits associated with antisocial behavior, that is, impulsivity, irritability, and/or callous–unemotional traits. In this study TDI was investigated in a large adolescent group with varying levels of antisocial behavior. Methods: Participants consisted of 195 adolescents (67 with CD, 77 in a psychiatric comparison group and 51 typically developing adolescents). Participants performed a temporal discounting task and individual differences were measured through the Connors rating scale for attention-deficit/hyperactivity disorder (impulsivity), Affective Reactivity Index (irritability), and Inventory of Callous–Unemotional traits. Results: The adolescents with CD and those in the psychiatric comparison group showed significantly greater TDI than typically developing adolescents. However, these group differences were abolished when dimensional covariates were included. Irritability was significantly associated with TDI. Conclusions: We conclude that TDI reflects a transdiagnostic form of dysfunction that particularly manifests in adolescents with increased irritability.

Objective: Despite the advances in the field of neuroscience, many questions remain regarding the mechanisms of anxiety, as well as moderators of treatment outcome. Long-term adverse outcomes for anxious youth may relate to pathophysiologically based information processing patterns and self-referential beliefs, such as self-efficacy. In fact, there are no studies highlighting the relationship between self-efficacy and neurocircuitry in youth. The purpose of this study was to explore the relationships between self-efficacy, brain morphometry, and youth anxiety. Methods: Parent, child, and clinician ratings of anxiety symptoms and child-reported self-efficacy were analyzed in a sample of 8- to 17-year-old youth (n = 51). Measures were collected from all youth at baseline and during and after treatment for the patients. Anxious patients (n = 26) received 12 sessions of cognitive behavioral therapy (CBT). Moreover, imaging data obtained from all participants before treatment were utilized in analyses. Results: Patients reported lower self-efficacy than healthy volunteers. Across the entire sample, anxiety was negatively related to total, social, and emotional efficacy. Both social and emotional efficacy predicted anxiety posttreatment. In addition, social efficacy predicted social anxiety symptoms posttreatment and social efficacy increased across treatment. There were no significant relations between self-efficacy and neurocircuitry. Conclusions: Self-efficacy is an important treatment target for anxious youth. Although self-efficacy was not related to brain morphometry, self-efficacy beliefs may constitute an important mechanism through which CBT and psychopharmacological interventions decrease fear and anxiety symptoms in youth.

Objective: Socially anxious adolescents report distress during social decision-making, wherein their favorable view of peers directly conflicts with their expectation to be viewed negatively by peers; a phenomenon we refer to as “mismatch bias.” The present study utilizes a novel paradigm with dynamic social stimuli to explore the correlates of mismatch biases in anxious and healthy youth. Method: The behavioral and neural correlates of mismatch biases were assessed in healthy (N = 17) and anxious (N = 14) youth during functional MRI. Participants completed a novel task where they viewed silent videos of unknown peers. After viewing each video, participants appraised the social desirability of the peer (“How much do you think you would like them [if you met them]”) or predicted how socially desirable the peer would find them (“How much do you think they would like you [if you met them]”). Each participant's mismatch bias was calculated as the difference between their appraisal of peers and their prediction of peers' appraisal of them. Results: We found that anxious youth exhibited mismatch bias: they rated unknown peers as more desirable than they predicted peers would rate them. This effect was not present in the healthy group. Mismatch biases were associated with increased engagement of the ventrolateral prefrontal cortex (vlPFC), a region broadly involved in flexible cognitions and behavioral selection. In addition, greater mismatch biases and vlPFC activation during mismatch biases were associated with more severe anxiety symptoms. Conclusions: The findings highlight the importance of understanding mismatch biases to inform treatments that target distress elicited by discrepant social appraisals in anxious youth.

Objective: Irritability in disruptive mood dysregulation disorder (DMDD) may be associated with a biased tendency to judge ambiguous facial expressions as angry. We conducted three experiments to explore this bias as a treatment target. We tested: 1) whether youth with DMDD express this bias; 2) whether judgment of ambiguous faces can be altered in healthy youth by training; and 3) whether such training in youth with DMDD is associated with reduced irritability and associated changes in brain function.Methods: Participants in all experiments made happy versus angry judgments of faces that varied along a happy to angry continuum. These judgments were used to quantify a "balance point," the facial expression at which a participant's judgment switches from predominantly happy to predominantly angry. We first compared balance points in youth with DMDD (n = 63) versus healthy youth (n = 26). We then conducted a double-blind, randomized controlled trial of active versus sham balance-point training in 19 healthy youth. Finally, we piloted open, active balance-point training in 14 youth with DMDD, with 10 completing an implicit functional MRI (fMRI) face-emotion processing task.Results: Relative to healthy youth, DMDD youth manifested a shifted balance point, expressed as a tendency to classify ambiguous faces as angry rather than happy. In both healthy and DMDD youth, active training is associated with a shift in balance point toward more happy judgments. In DMDD, evidence suggests that active training may be associated with decreased irritability and changes in activation in the lateral orbitofrontal cortex.Conclusions: These results set the stage for further research on computer-based treatment targeting interpretation bias of angry faces in DMDD. Such treatment may decrease irritability and alter neural responses to subtle expressions of happiness and anger.

In light of the current controversy about whether severe temper outbursts are diagnostic of mania in young children, we conducted a study to characterize such children, focusing on mania and other mood disorders, emotion regulation, and parental psychiatric history.Study participants included 51 5-9-year-old children with frequent, impairing outbursts (probands) and 24 non-referred controls without outbursts. Parents completed a lifetime clinical interview about their child, and rated their child's current mood and behavior. Teachers completed a behavior rating scale. To assess emotion regulation, children were administered the Balloons Game, which assesses emotion expressivity in response to frustration, under demands of high and low regulation. Parental lifetime diagnoses were ascertained in blind clinical interviews.No child had bipolar disorder, bipolar disorder not otherwise specified (NOS), or major depression (MDD). The most prevalent disorder was oppositional defiant disorder (88.2%), followed by attention-deficit/hyperactivity disorder (74.5%), anxiety disorders (49.0%), and non-MDD depressive disorders (33.3%). Eleven probands (21.6%) met criteria for severe mood dysregulation. During the Balloons Game, when there were no demands for self-regulation, children with severe outbursts showed reduced positive expressivity, and also showed significant deficits in controlling negative facial expressions when asked to do so. Anxiety disorders were the only diagnoses significantly elevated in probands' mothers.Overall, young children with severe temper outbursts do not present with bipolar disorder. Rather, disruptive behavior disorders with anxiety and depressive mood are common. In children with severe outbursts, deficits in regulating emotional facial expressions may reflect deficits controlling negative affect. This work represents a first step towards elucidating mechanisms underlying severe outbursts in young children.

The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity.Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy.There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP's developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind.EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace.

Irritability is both a normal developmental phenomenon and a common psychiatric symptom in children. In psychiatric nosology, a distinction is made between chronic and episodic irritability. This study examines the validity of this distinction.A sample of 776 youths received Diagnostic and Statistical Manual of Mental Disorders (DSM)-based structured interviews at three time points. Questions regarding episodic and chronic irritability were used to create scales measuring these constructs; associations with age, gender, and diagnosis were examined.Episodic and chronic irritability differed in their associations with age. The longitudinal stability within irritability type was stronger than between types. In longitudinal analyses, chronic irritability at time 1 (mean age 13.8 +/- 2.6 years) predicted attention deficit/ hyperactivity disorder at time 2 (mean age 16.2 +/- 2.8 years) and major depression at time 3 (mean age 22.1 +/- 2.7 years). Episodic irritability at time 1 predicted simple phobia and mania at time 2.Episodic and chronic irritability in adolescents appear to be stable, distinct constructs. Further research is needed to elucidate the longitudinal associations of each with specific psychiatric diagnoses.

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.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).Children and adolescents with anxiety disorders exhibited significantly poorer performance on the face-emotion recognition task compared to healthy controls (z = 2.2; p0.05). This difference was found only for expressions posed by adults but not children.Reduced accuracy on a face-emotion recognition test is consistent with perturbed amygdala function in pediatric anxiety disorders.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.

The autism spectrum disorders (ASDs) can present with symptoms commonly found in mood and anxiety disorders. The Social Communication Questionnaire (SCQ), Children's Communication Checklist (CCC-2), and the Social Reciprocity Scale (SRS) were used to screen children in a mood disorders research clinic setting for symptoms of ASD. Ninety-three patients (mean age, 12.7 +/- 2.8 years; percent male, 63%) completed at least one scale, and 50 children completed all three. The prevalence of those screening positive for a possible ASD on one instrument was 62% and on all three measures was 8%. Fifty-seven percent (n = 21/37; odds ratio, 4.59 [95% confidence interval (CI) = 1.40-15.11]) of those scoring in the "ASD-likely" range on the SRS scored in that range on the CCC-2. Only 16% (n = 6/37; odds ratio, not significant (NS)) of those scoring in the ASD-likely range on the SRS, and 14% (n = 5/37; odds ratio, NS) of those scoring in the ASD-likely range on the CCC-2, scored similarly on the SCQ. These results demonstrate a need to develop valid and reliable instruments to screen for ASDs in children presenting outside of ASD clinics.

We assessed the use of mood stabilizers, stimulants, antipsychotic medication, and selective serotonin reuptake inhibitors in children being treated in the community for bipolar disorder (BPD). One hundred eleven patients were screened via parent phone interview for possible inclusion in a phenomenological study of BPD. Data were obtained on the patients' medication trials and side effects. The results of the study indicated that children and adolescents who carry a diagnosis of BPD are treated with a mean of 3.40 +/- 1.48 medications and have had a mean of 6.32 +/- 3.67 trials of psychotropic medication in the past. Ninety-eight percent have had a trial of a mood stabilizer or anticonvulsant, with the most common being valproate (79%), lithium (51%), and gabapentin (29%).

Researchers debate whether the diagnostic criteria for mania should differ between children and adults. Specifically, although the Diagnostic and Statistical Manual of Mental Disorders (fourth edition; DSM-IV) requires episodic mood changes, children commonly are diagnosed as manic on the basis of chronic irritability. In this preliminary study, children carrying a diagnosis of bipolar disorder (BPD) in the community were classified as having either episodic or chronic symptoms. We hypothesized that the episodic group would be more likely to have a history of psychosis and a parental history of BPD, whereas the chronic group would be more likely to have conduct disorder.Parents of children carrying the BPD diagnosis were interviewed on the telephone to obtain psychiatric and family histories. Children were considered episodic (n = 34) if they had a history of one or more DSM-IV manic/hypomanic episodes meeting full duration criteria and chronic (n = 53) if they had no discernable episodes.The episodic group was more likely to have had psychosis, parental history of BPD, and to have experienced each manic symptom except for irritability and psychomotor agitation. Children in the episodic group were also more likely to have had a depressive episode meeting full DSM-IV criteria and were more likely to have made a suicide attempt. Children in the chronic group were not more likely to meet criteria for conduct disorder but were more likely to exhibit violence toward others.These preliminary data indicate that, among children being treated for BPD in the community, those with discrete episodes of mania may be more likely to have a lifetime history of psychosis and a parental history of BPD. The latter hypothesis should be tested in a sample where relatives are interviewed directly.

To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents.The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities (including adult psychiatrists with expertise in bipolar disorder) and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing: (1) inclusion/exclusion criteria, (2) investigator training needs and site selection, (3) assessment and outcome measures, (4) protocol design and ethical issues unique to trials involving children/adolescents, and (5) regulatory agency perspectives on these deliberations.Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10-17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/rage and cognitive function, while using the best available instruments (e.g., Young Mania Rating Scale) in the interim.Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties.

The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD) by Leibenluft, has been the focus of increasing concern. We conducted the first randomized double-blind, placebo-controlled trial in SMD youth, choosing lithium on the basis of its potential in treating irritability and aggression and neuro-metabolic effects.SMD youths 7-17 years were tapered off their medications. Those who continued to meet SMD criteria after a 2-week, single-blind, placebo run-in were randomized to a 6-week double-blind trial of either lithium (n = 14) or placebo (n = 11). Clinical outcome measures were: (1) Clinical Global Impressions-Improvement (CGI-I) score less than 4 at trial's end and (2) the Positive and Negative Syndrome Scale (PANSS) factor 4 score. Magnetic resonance spectroscopy (MRS) outcome measures were myoinositol (mI), N-acetyl-aspartate (NAA), and combined glutamate/glutamine (GLX), all referenced to creatine (Cr).In all, 45% (n = 20/45) of SMD youths were not randomized due to significant clinical improvement during the placebo run-in. Among randomized patients, there were no significant between-group differences in either clinical or MRS outcome measures.Our study suggests that although lithium may not result in significant clinical or neurometabolic alterations in SMD youths, further SMD treatment trials are warranted given its prevalence.

There has been limited research on anxiety in pediatric bipolar disorder (BPD). Adult BPD studies suggest comorbid anxiety disorders are common and impact treatment outcome. We explored the association of comorbid anxiety with two phenotypes of pediatric BPD.We studied two groups of children. The first group (BPD; N = 31) represents the "narrow phenotype" of pediatric BPD, meeting stringent DSM-IV criteria for mania, including duration and elevated/expansive mood. The second group (ED; N = 32) exhibited chronic, non-episodic irritability without elation or grandiosity ("broad phenotype").Both samples demonstrate high prevalence of anxiety (BPD 77.4%; ED 46.9%). In the BPD sample, anxiety predates BPD onset, and those with comorbid anxiety have earlier age of onset of BPD than those without. Children with BPD plus anxiety have more hospitalizations than those without anxiety. ED subjects with and without comorbid anxiety did not differ with respect to onset of ED symptoms or number of hospitalizations.Narrow and broad phenotype BPD children have high rates of comorbid anxiety, although only in the narrow phenotype group is comorbid anxiety associated with greater functional impairment BPD plus comorbid anxiety may represent a particularly severe phenotype of pediatric BPD.