Biomedical subjects

Ellen Leibenluft

Publications and source records attributed to Ellen Leibenluft.

At least 37 records · Page 2Linked to original sources

PubMed2005

Emotion recognition deficits in pediatric anxiety disorders: implications for amygdala research.

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.

Adolescent↗

PubMed2005

Memory and learning in pediatric bipolar disorder.

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.

Bipolar Disorder↗

PubMed2005

An investigation of prepulse inhibition in pediatric bipolar disorder.

OBJECTIVES: Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, have been noted in psychopathologies including schizophrenia and adult bipolar disorder (BPD). Sensorimotor gating deficits may contribute to the emotional and behavioral dysregulation characteristic of pediatric BPD. The current study investigated possible PPI deficits in children with BPD. METHODS: Sixteen children with BPD (medicated, euthymic and non-psychotic) were compared with 13 control subjects on the magnitude of startle habituation, startle-alone response, and inhibition of startle following a 60 or 120-ms prepulse. RESULTS: Both groups displayed startle inhibition by a prepulse, with no significant between-group differences on the magnitude of inhibition after the 60- or 120-ms prepulse. In addition, there were no between-group differences on habituation or baseline startle response. PPI level was not significantly correlated with mood symptoms and did not differ based on comorbid attention deficit hyperactivity disorder. CONCLUSIONS: A lack of PPI deficits in our pediatric bipolar sample contrasts with previous results in adult bipolar and schizophrenic samples. These negative results may reflect the fact that our sample was medicated and was neither acutely manic nor psychotic. Deficits in sensorimotor gating may not be implicated in the emotional and behavioral dysregulation in pediatric BPD.

Adolescent↗

PubMed2005

Using affect-modulated startle to study phenotypes of pediatric bipolar disorder.

OBJECTIVES: Affective neuroscience research that investigates core symptoms of pediatric bipolar disorder (PBD) may be effective in differentiating PBD phenotypes. The current study used affect-modulated startle to examine potential differences in reactivity to emotional stimuli (reward and punishment) in narrow and broad phenotype PBD and controls. METHODS: Thirty children meeting DSM-IV bipolar disorder criteria (i.e. narrow phenotype PBD with defined manic episodes with elevated/expansive mood), 19 children meeting criteria for severe mood dysregulation (i.e. broad phenotype with chronic irritability, hyper-reactivity, and hyperarousal), and 19 controls completed a lottery startle paradigm involving reward (money) and punishment (loud noise). Startle probes were presented during anticipation of the emotional stimulus, immediately following the presentation of the stimulus, or during return to baseline following the stimulus. RESULTS: By self-report, patients and controls found the putative punishment to be preferable to the neutral condition. In the reward condition, patient samples reported greater arousal than did controls, but no between-group differences were found on the magnitude of startle response during the reward, punishment, or neutral conditions. CONCLUSIONS: The failure to find differences in affect-modulated startle between control children and those with narrow or broad PBD phenotypes speaks to the methodological challenges associated with studying reward mechanisms in PBD. Alternative paradigms that focus on different aspects of reward mechanisms are discussed.

Acoustic Stimulation↗

PubMed2005

Deficits on a probabilistic response-reversal task in patients with pediatric bipolar disorder.

OBJECTIVE: Patients with bipolar disorder become hyperhedonic when manic and anhedonic when depressed; therefore, it is important to test whether patients with bipolar disorder show deficits on behavioral paradigms exploring reward/punishment mechanisms. METHOD: A probabilistic response-reversal task was administered to 24 bipolar children and 25 comparison subjects. RESULTS: Patients made more errors during probabilistic reversal, took longer to learn the new reward object, and were less likely to meet the learning criterion. CONCLUSIONS: Children with bipolar disorder may have a reversal learning deficit.

Adolescent↗

PubMed2005

Deficits in social cognition and response flexibility in pediatric bipolar disorder.

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.

Adolescent↗

PubMed2004

Experience-dependent plasticity for attention to threat: Behavioral and neurophysiological evidence in humans.

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.

Adolescent↗

PubMed2004

Mothers' neural activation in response to pictures of their children and other children.

BACKGROUND: Considerable literature has focused on neural responses evoked by face viewing. We extend that literature and explore the neural correlates of maternal attachment with an fMRI study in which mothers view photographs of their own children. METHOD: Seven mothers performed a one-back repetition detection task while viewing photographs of their own child, friends of their child, unfamiliar children, and unfamiliar adults. RESULTS: Viewing one's own child versus a familiar child was associated with activation in the amygdala, insula, anterior paracingulate cortex, and posterior superior temporal sulcus (STS). Viewing familiar versus unfamiliar children elicited increased activation in regions associated with familiarity in adults. Viewing unfamiliar children versus unfamiliar adults was associated with activation in the fusiform gyrus, intraparietal sulcus, precuneus, and posterior STS. CONCLUSIONS: The sight of one's own child versus that of a familiar child activates regions that mediate emotional responses (amygdala, insula) and are associated with theory of mind functions (anterior paracingulate cortex, posterior superior temporal sulcus). These activations may reflect the intense attachment, vigilant protectiveness, and empathy that characterize normal maternal attachment. The sight of an unfamiliar child's face compared with that of an unfamiliar adult engages areas associated with attention as well as face perception.

Adult↗

PubMed2004

A developmental examination of gender differences in brain engagement during evaluation of threat.

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.

Adolescent↗

PubMed2004

Neuropsychological performance in pediatric bipolar disorder.

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.

Adolescent↗

PubMed2004

Reward-related processes in pediatric bipolar disorder: a pilot study.

BACKGROUND: Neuropsychological research on children with bipolar disorder (BPD) is scarce. Here, we examine reward-related behaviors in children with BPD using a Wheel of Fortune task in which subjects could win or lose money depending on their decisions. The intent of this work was to investigate performance differences between BPD and healthy children on a task that could be used in an fMRI environment to inform the neural substrates of reward processes in BPD. This study has no direct clinical implications. We hypothesized that relative to healthy children, children with BPD would select risky options more frequently, be less confident in a favorable outcome, and report stronger emotional responses to outcomes. METHODS: Forty-four children (22 BPD; 22 control) were compared on (i) decision-making with varying levels of risk, (ii) level of confidence in favorable outcomes, and (iii) responses to feedback. The task included a win-no win version and a lose-no lose version. RESULTS: Patterns of selection did not differ between groups. In the lose-no lose task, BPD patients were less confident than controls in favorable outcomes. BPD patients expressed greater dissatisfaction than controls at not winning in win-no win, and greater satisfaction than controls at not losing in lose-no lose. LIMITATIONS: Limitations of this study included that the children with BPD were mostly in a depressed state, were medicated, and had co-morbid disorders. CONCLUSIONS: This is the first experimental study to examine associations between pediatric BPD and reward-related behaviors. Although we failed to detect abnormalities in risky decision-making in children with BPD, we found significant differences between groups in both confidence ratings and response to feedback, consistent with our predictions. Our ultimate goal is to use this task in the fMRI environment to gain a better understanding of the neural correlates of reward-related processes in pediatric BPD.

Adolescent↗

PubMed2004

Social and emotional attachment in the neural representation of faces.

To dissociate the role of visual familiarity from the role of social and emotional factors in recognizing familiar individuals, we measured neural activity using functional magnetic resonance imaging (fMRI) while subjects viewed (1) faces of personally familiar individuals (i.e. friends and family), (2) faces of famous individuals, and (3) faces of strangers. Personally familiar faces evoked a stronger response than did famous familiar faces and unfamiliar faces in areas that have been associated with 'theory of mind', and a weaker response in the amygdala. These response modulations may reflect the spontaneous activation of social knowledge about the personality and attitudes of close friends and relatives and the less guarded attitude one has around these people. These results suggest that familiarity causes changes in neural response that extend beyond a visual memory for a face.

Adult↗

PubMed2004

Choice selection and reward anticipation: an fMRI study.

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.

Adult↗

PubMed2004

Management of bipolar disorder during pregnancy and the postpartum period.

OBJECTIVE: Bipolar disorder affects 0.5%-1.5% of individuals in the United States. The typical age at onset is late adolescence or early adulthood, placing women at risk for episodes throughout their reproductive years. General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when these guidelines are applied in the treatment of peripartum women. The authors summarize knowledge regarding the management of bipolar disorder during pregnancy and the postpartum period, with a focus on managing mania, hypomania, and the psychotic components of the illness. METHOD: An expert panel reviewed articles that address the management of bipolar disorder and the consequences of the use of mood stabilizers during pregnancy, and a consensus document was generated. RESULTS: The treatment of bipolar disorder in pregnant women involves significant challenges. Some mood stabilizers, e.g., sodium valproate and carbamazepine, are human teratogens. On the other hand, the teratogenicity associated with lithium may have been overestimated in the past. CONCLUSIONS: Since treatment can be managed most effectively if pregnancy is planned, clinicians should discuss the issue of pregnancy and its management with every bipolar disorder patient who has childbearing potential, regardless of future reproductive plans. Additional research should address the risks of disturbed sleep to pregnant and postpartum women with bipolar disorder, as well as structural and behavioral consequences to offspring when mood stabilizers are used during pregnancy. Longitudinal and cohort studies can promote these efforts. Given the rate of bipolar disorder in the general population, research efforts will need to be broad based and include multiple collaborating centers.

Adolescent↗

PubMed2003

Researching the pathophysiology of pediatric bipolar disorder.

We suggest that the core feature of bipolar disorder (BPD) is marked state fluctuations. The pathophysiology of switches into depressed, irritable, and extreme positive valence states requires study, with the latter deserving particular focus because it represents a pathognomonic feature of BPD in both adults and children. Hypotheses regarding the pathophysiology of pediatric BPD must account for these marked state fluctuations as well as for specific developmental aspects of the illness. These developmental aspects include marked irritability (in addition to euphoria and depression) and very rapid cycles, along with high rates of attention-deficit/hyperactivity disorder. We review research on neural mechanisms underlying positive valence states and state regulation, focusing on those data relevant to BPD and to development. Researchers are beginning to explore the response of manic patients and control subjects to positive affective stimuli, and considerable research in both nonhuman primates and humans has focused on the cortico-limbic-striatal circuits mediating responses to rewarding stimuli. In control subjects, positive affect affects cognition, and data indicate that prefrontal electroencephalogram asymmetry may differ between control subjects with consistently positive affect and those with more negative affect; however, this latter generalization may not apply to adolescents. With regard to the pathophysiology of state switching in pediatric BPD, data in control subjects indicating that attention regulation plays a role in emotion regulation may be germane. In addition, research detailing physiologic and psychological responses to negative emotional stimuli in bipolar patients and control subjects may increase our understanding of the mechanisms underlying both irritability and rapid cycling seen in children with BPD. Potential foci for research on the pathophysiology of pediatric BPD include reactivity to standardized positive and negative emotional stimuli, and the interaction between emotion regulation and attentional processes.

Adolescent↗

PubMed2003

Adolescent immaturity in attention-related brain engagement to emotional facial expressions.

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.

Adolescent↗

PubMed2003

Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: report of a consensus conference.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

PubMed2003

Clinical correlates of episodicity in juvenile mania.

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

Adolescent↗