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Ellen Leibenluft

Publications and source records attributed to Ellen Leibenluft.

At least 19 recordsLinked to original sources
PubMed2007

Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.

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.

Adolescent↗
PubMed2007

Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder.

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.

Adolescent↗
PubMed2006

Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children.

BACKGROUND: Controversy concerning the diagnosis of pediatric bipolar disorder (BD) has focused attention on children with chronic irritability and hyperarousal. This syndrome has been called the "broad BD phenotype" or severe mood dysregulation (SMD). This study examines prevalence, concurrent Axis I diagnoses, and longitudinal outcome of SMD in an epidemiologic sample. METHODS: Data were drawn from the Great Smoky Mountains Study, a longitudinal epidemiological study. Items from the Child and Adolescent Psychiatric Assessment were used to generate SMD criteria. RESULTS: Among 1420 children, the lifetime prevalence of SMD in children ages 9-19 was 3.3%. Most (67.7%) SMD youth had an Axis I diagnosis, most commonly attention-deficit/hyperactivity disorder (26.9%), conduct disorder (25.9%), and/or oppositional defiant disorder (24.5%). In young adulthood (mean age 18.3 +/- 2.1 years), youth who met criteria for SMD in the first wave (mean age 10.6 +/- 1.4 years) were significantly more likely to be diagnosed with a depressive disorder (odds ratio 7.2, confidence interval 1.3-38.8, p = .02) than youth who never met criteria for SMD. CONCLUSIONS: Severe mood dysregulation is relatively common in childhood and predicts risk for early adulthood depressive disorders. Research should continue to explore the course of illness in children with SMD.

Adolescent↗
PubMed2006

fMRI predictors of treatment outcome in pediatric anxiety disorders.

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.

Adolescent↗
PubMed2006

Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder.

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.

Adolescent↗
PubMed2006

Increased amygdala activity during successful memory encoding in adolescent major depressive disorder: An FMRI study.

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.

Adolescent↗
PubMed2006

Emotion regulation in children and adolescents: boundaries between normalcy and bipolar disorder.

Much controversy has surrounded the diagnosis of bipolar disorder (BD) in children and adolescents. However, recent work from an affective neuroscience perspective has advanced what is known about the boundaries of emotion regulation in BD compared to typically developing youth. In this article, we first briefly review the clinical issues that have contributed to this diagnostic controversy. Second, we discuss our phenotyping system, which can be used to guide neurobiological research designed to address these controversial issues. Third, we review what is known about the fundamentals of emotion regulation in human and nonhuman primate models. Fourth, we present recent data demonstrating how children and adolescents with BD differ from those without psychopathology on measures of emotion regulation. Taken as a whole, this work implicates a neural circuit encompassing the prefrontal cortex, amygdala, and striatum in the pathophysiology of pediatric BD.

Adolescent↗
PubMed2006

Chronic versus episodic irritability in youth: a community-based, longitudinal study of clinical and diagnostic associations.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗
PubMed2006

Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder.

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.

Adolescent↗
PubMed2005

Neurologic examination abnormalities in children with bipolar disorder or attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently comorbid and overlapping diagnoses. To move beyond diagnosis toward unique pathophysiology, we evaluated both ADHD and BPD children for neurologic examination abnormalities (NEAs) in comparison with normal control (NC) children. METHODS: We performed the Revised Physical and Neurological Examination for Soft Signs in three groups (ADHD, BPD, NC). Then, a rater blind to diagnosis evaluated their motor performance. Results were analyzed with a multiple analysis of covariance. RESULTS: Subjects with ADHD were impaired on repetitive task reaction time. In contrast, pediatric BPD subjects, both with and without comorbid ADHD, were impaired on sequential task reaction time. CONCLUSIONS: This differential pattern of NEAs by diagnosis suggests pathophysiologic differences between ADHD and BPD in children. Repetitive motor performance requires inhibition of nonrelevant movements; ADHD subjects' impairment in this domain supports the hypothesis that ADHD involves a core deficit of fronto-striato-basal ganglia neurocircuitry. In contrast, BPD subjects' impaired sequential motor performance is consistent with behavioral data showing impaired attentional set-shifting and reversal learning in BPD subjects. Further study, going beyond symptom description to determine pathophysiologic differences, is required to refine neuronal models of these often comorbid diagnoses.

Adolescent↗
PubMed2005

The impact of reward, punishment, and frustration on attention in pediatric bipolar disorder.

BACKGROUND: Theories in affective neuroscience suggest that mood disorders involve perturbations in attention-emotion interactions. We tested the hypothesis that frustration adversely impacts attention and behavior in children with bipolar disorder (BPD). METHODS: Thirty-five children with BPD and 26 normal control subjects completed: 1) a Posner attention task with feedback but no contingencies; 2) an affective Posner with contingencies; and 3) an affective Posner that used rigged feedback to induce frustration. Reaction time (RT) and event-related potential (ERP) data were collected. RESULTS: At baseline (task 1), there were no between-group differences in behavior or ERPs. Children with BPD exhibited reduced parietal P3 amplitude on task 3 only. On trials occurring after negative feedback, control subjects showed decreased RT when contingencies were introduced (task 2), whereas BPD subjects did not. CONCLUSIONS: The introduction of contingencies was associated with impaired performance of children with BPD, suggesting deficits in their ability to adapt to changing contingencies. In addition, frustration was associated with disrupted attention allocation in children with BPD. We hypothesize that children with BPD inappropriately deployed attention to their internal frustration rather than to the task, causing impaired performance.

Adolescent↗
PubMed2005

Selective reduction in amygdala volume in pediatric anxiety disorders: a voxel-based morphometry investigation.

BACKGROUND: Significant controversy has emerged concerning pediatric anxiety disorders. Some researchers question the justification for diagnosing and treating pediatric anxiety disorders, owing to concerns about the inappropriate medicalization of social problems. Others note the importance of diagnosis and treatment, given that pediatric anxiety disorders represent a strong risk factor for serious adult mental disorders. We examine the neural correlates of pediatric anxiety disorders, to consider the validity of the categorization scheme used in recent treatment studies. METHODS: Using inclusion criteria derived from recent treatment trials, we compared gray matter volume throughout the brain in children with and without anxiety. Morphometric analyses used optimized voxel-based morphometry, an automated method for examining structural changes throughout the brain. RESULTS: Reductions in left amygdala gray matter volume were noted for patients with anxiety disorders relative to comparison subjects. CONCLUSIONS: We discuss implications of these findings for current controversies.

Adolescent↗
PubMed2005

Amygdala and nucleus accumbens in responses to receipt and omission of gains in adults and adolescents.

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.

Adolescent↗
PubMed2005

Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study.

CONTEXT: While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD. OBJECTIVE: To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex. DESIGN: Ongoing study of the pathophysiology of pediatric BPD. SETTING: Intramural National Institute of Mental Health; approved by the institutional review board. Patients Pediatric subjects with BPD (n = 20) with at least 1 manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ. MAIN OUTCOME MEASURES: With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry. RESULTS: Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex. CONCLUSIONS: Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD.

Adolescent↗
PubMed2005

The social re-orientation of adolescence: a neuroscience perspective on the process and its relation to psychopathology.

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.

Adolescent↗
PubMed2005

Autism spectrum traits in children with mood and anxiety disorders.

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.

Adolescent↗
PubMed2005

Comorbid anxiety in phenotypes of pediatric bipolar disorder.

OBJECTIVE: 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. METHODS: 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"). RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗