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Biomedical subjects

Daniel P Dickstein

Publications and source records attributed to Daniel P Dickstein.

14 recordsLinked to original sources
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

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↗
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

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

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

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↗
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

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

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↗