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Biomedical subjects

Joseph Biederman

Publications and source records attributed to Joseph Biederman.

At least 163 records · Page 9Linked to original sources
PubMed2003

Can adults with attention-deficit/hyperactivity disorder be distinguished from those with comorbid bipolar disorder? Findings from a sample of clinically referred adults.

BACKGROUND: Despite data describing the overlap of attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) in youth, little is known about adults with these co-occurring disorders. We now evaluate the clinical characteristics of referred adults with (n = 24) and without BPD (n = 27). METHODS: Referred adults to clinical trials of ADHD were evaluated by psychiatric evaluation using DSM-IV criteria. Structured psychiatric interviews were used to systematically assess adult and childhood disorders. RESULTS: The vast majority of patients with ADHD plus BPD had bipolar II disorder (88%). Adults with ADHD plus BPD had higher rates of the combined subtype of ADHD compared to ADHD without BPD (chi(2) = 8.7, p =.003), a greater number of DSM-IV ADHD symptoms (14.8 +/- 2.9 and 11.4 +/- 4.0; t = -3.4, p <.01), more attentional symptoms of ADHD (8.1 +/- 1.4 and 6.8 +/- 2.1; t = -2.5, p <.02; trend), poorer global functioning (47 +/- 5.9 and 52 +/- 7.4, t = 2.6, p <.02; trend), and additional comorbid psychiatric disorders (3.7 +/- 2.5 and 2.0 +/- 1.9; t = -2.9, p <.01). CONCLUSIONS: These results suggest that adults with ADHD plus BPD have prototypic symptoms of both disorders, suggesting that both disorders are present and are distinguishable clinically.

Adult↗
PubMed2003

Can a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program.

Our intent was to investigate systematically the overlap between conduct disorder (CD) and bipolar disorder (BPD). We hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the two disorders would have correlates of both. Results from a series of programmatic studies examining phenotypic features of bipolar and conduct disorder alone or combined in probands and relatives were evaluated within and without the context of ADHD. Examination of the clinical features, patterns of psychiatric comorbidity, functioning in multiple domains, and familiality showed that children with CD and BPD had similar features of each disorder irrespective of the comorbidity with the other disorder. Our data suggest that when BPD and CD co-occur in children, both are correctly diagnosed. In these comorbid cases, CD symptoms should not be viewed as secondary to BPD, and manic symptoms should not be viewed as secondary to CD.

Adolescent↗
PubMed2003

A preliminary meta-analysis of the child behavior checklist in pediatric bipolar disorder.

BACKGROUND: A possible explanation for the ongoing controversy surrounding pediatric bipolar disorder is that differences in assessment methodologies lead to conflicting results. One way to address methodological differences in assessment across studies is to use a single standardized assessment of psychopathology to calibrate the findings reported in different studies. To this end, we conducted a meta-analysis of several studies that have employed the Child Behavior Checklist in the assessment of children with a diagnosis of bipolar disorder. METHODS: MEDLINE was searched for all publications that utilized the Child Behavior Checklist in addition to structured diagnostic interviews to assess pediatric bipolar disorder. Random effects models were used to calculate combined estimates of Child Behavior Checklist clinical subscales. RESULTS: Children with bipolar disorder had scaled scores of >70 in the Aggression, Attention Problems, and Anxious/Depressed subscales of the Child Behavior Checklist. The Child Behavior Checklist was useful in distinguishing bipolar from attention-deficit/hyperactivity disorder subjects. CONCLUSIONS: While there was a significant heterogeneity in estimates between studies, a consistent pattern of elevations in inattention/hyperactivity, depression/anxiety, and aggression was identified.

Adolescent↗
PubMed2003

Behavioral inhibition and disinhibition as hypothesized precursors to psychopathology: implications for pediatric bipolar disorder.

Attention has been devoted over the past two decades to the identification of temperamental risk factors for child psychopathology. These qualities, evident in toddlerhood or earlier, have the advantage of being measurable in standardized laboratory observations well before children reach the age of onset or diagnosis of psychiatric disorders. Our group's programmatic research over the past 15 years, and that of others, has provided evidence linking "behavioral inhibition to the unfamiliar" in toddlerhood or early childhood with later social anxiety disorder. In addition, recent results by our group have suggested that "behavioral disinhibition" in early childhood, measured by the same laboratory methods, may be linked with later disruptive behavior and comorbid mood disorders. In this article, we discuss our approach to the study of temperamental precursors to disorders in high-risk children, summarize the literature linking behavioral inhibition and disinhibition to later psychopathology, and suggest directions to take in applying this methodology to the search for temperamental precursors to pediatric bipolar disorder.

Adolescent↗
PubMed2003

Convergence between structured diagnostic interviews and clinical assessment on the diagnosis of pediatric-onset mania.

BACKGROUND: Uncertainties remain as to the utility of structured diagnostic methodology to aid in the diagnosis of manic symptomatology in youth. To this end, this study compared structured diagnostic interview based diagnoses of mania in children and adolescents with that of an expert clinician. METHODS: We separately and independently assessed 69 youths recruited for a study of mania in childhood, all but 2 of whom experienced mania, with a structured diagnostic interview administered by trained psychometricians and a clinical assessment by a board-certified child and adolescent psychiatrist (JW) who was blind to the structured interview results. RESULTS: Structured interviews and clinical evaluations converged in all but two cases (67 of 69 or 97% agreement). In one discrepant case, the structured interview diagnosed a full case of mania, but the clinical interview diagnosed cyclothymia/subthreshold mania; in the other discrepant case, the structured interview failed to diagnose mania, but the clinical interview did diagnose mania. CONCLUSIONS: In children referred for evaluation of suspected bipolar disorder, a structured interview diagnosis of mania is very likely to be corroborated by a clinical interview.

Adolescent↗
PubMed2003

Dopamine transporter gene, response to methylphenidate and cerebral blood flow in attention-deficit/hyperactivity disorder: a pilot study.

The homozygosity of the 10-repeat allele at dopamine transporter gene (DAT1) seems to be associated with a poor response to methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD). This pilot study aimed to simultaneously assess polymorphisms at DAT1, response to MPH, and neuroimaging. Only ADHD children with at least a moderate response to MPH were included. Significantly higher regional cerebral blood flows assessed by single photon emission computerized tomography (SPECT) were detected in medial frontal and left basal ganglia areas in children with homozygosity for the 10-repeat allele at DAT1 gene (n = 4) than in children without this genotype (n = 4) (P < 0.05). These findings provide a preliminary connection between pharmacogenetics and neurobiological investigations on stimulant treatment of ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Does comorbid attention-deficit/hyperactivity disorder impact the clinical expression of pediatric obsessive-compulsive disorder?

What is the impact of attention-deficit/hyperactivity disorder (ADHD) on the phenotypic expression of pediatric obsessive-compulsive disorder (OCD). We examined phenotypic features, and functional and clinical correlates in youths with OCD, with and without comorbid ADHD, from a large sample of consecutively referred pediatric psychiatry patients. Although comorbid ADHD had no meaningful impact on the phenotypic expression or clinical correlates of OCD, it was associated with higher rates of compromised educational functioning compared with other OCD youths. Our findings suggest that the OCD phenotype runs true and is not impacted by comorbid ADHD in youths diagnosed with both OCD and ADHD. In such affected youths, both disorders contribute to morbid dysfunction and require treatment. More work is needed to determine whether OCD plus ADHD represents a developmentally and etiologically distinct form of the OCD syndrome.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Current concepts in the validity, diagnosis and treatment of paediatric bipolar disorder.

Despite ongoing controversy, the view that paediatric bipolar disorder is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. This research strongly suggests that paediatric bipolar disorder may not be rare but that it may be difficult to diagnose. Since children with bipolar disorder are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset bipolar disorder may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. As recommended by Robins and Guze [American Journal of Psychiatry (1970), 126, 983-987], a psychiatric disorder may be considered a valid diagnostic entity if it can be shown to have differentiating features, evidence of familiality, specific treatment responsivity and a unique course. The goal of this article is to review our work and the extant literature within this framework to describe the evidence supporting bipolar disorder in children as a valid clinical diagnosis.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

Does parental ADHD bias maternal reports of ADHD symptoms in children?

Within families, co-occurring attention-deficit/hyperactivity disorder (ADHD) in parents and children may be common. The authors evaluated the hypothesis that parental ADHD may lead to a reporting bias of ADHD symptoms in offspring. They combined 2 family case-controlled studies of ADHD using structured interviews. They compared rates of maternal reported ADHD symptoms among 3 groups of ADHD children: no parental ADHD (n = 231), mother with ADHD (n = 63), and father with ADHD (n = 57). With the exception of 1 symptom, the rates of reporting between groups did not differ. There was no evidence that the discrepancy between maternal reports and self-reports of symptoms differed by parental ADHD. Results were similar across child gender or referral status. These results do not support the notion that parental ADHD affects maternal reports of offspring ADHD.

Adolescent↗
PubMed2003

Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder.

OBJECTIVE: Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. This study was conducted, in part, to evaluate the single-dose and steady-state pharmacokinetics of atomoxetine in pediatric patients. METHODS: This was an open-label, dose-titration study in pediatric patients with attention deficit hyperactivity disorder. Eligible patients could elect to participate in a single-dose or steady-state discontinuation pharmacokinetic evaluation including serial plasma sample collection over 24 hours. Plasma concentrations of atomoxetine, 4-hydroxyatomoxetine, and N-desmethylatomoxetine were determined using an atmospheric pressure chemical ionization liquid chromatography/mass spectrometry/mass spectrometry assay. Pharmacokinetic parameters were calculated using noncompartmental analysis. RESULTS: Twenty-one cytochrome P450 2D6 extensive metabolizer patients participated in these single-dose and steady-state pharmacokinetic evaluations. Atomoxetine was rapidly absorbed, with peak plasma concentrations occurring 1 to 2 hours after dosing. Half-life averaged 3.12 and 3.28 hours after a single dose and at steady state, respectively. Minimal accumulation occurred in plasma after multiple twice-daily dosing in extensive metabolizer pediatric patients, as expected based on single-dose pharmacokinetics. As the dose (in mg/kg) increased, proportional increases in area under the curve were observed. CONCLUSIONS: The pharmacokinetics of atomoxetine in extensive metabolizer patients were well characterized over a wide range of doses in this study. Atomoxetine pharmacokinetics in pediatric patients and adult subjects were similar after adjustment for body weight.

Adolescent↗
PubMed2003

Impact of comorbidity on treatment response to paroxetine in pediatric obsessive-compulsive disorder: is the use of exclusion criteria empirically supported in randomized clinical trials?

OBJECTIVE: To examine the influence of psychiatric comorbidity on response and relapse rates in children and adolescents treated with paroxetine for obsessive-compulsive disorder (OCD). METHODS: Patients responding following 16 weeks of treatment (phase I) were randomized to continued paroxetine or to placebo for 16 additional weeks (phase II). OCD response (phase I) and relapse (phase II) criteria were based on the Clinical Global Impression-Improvement Scale and the Children's Yale-Brown Obsessive Compulsive Scale. The presence of OCD and other psychiatric disorders was ascertained using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview. RESULTS: At entry, 193 of 335 (57.6%) patients had at least one psychiatric disorder in addition to OCD, and 102 of 335 (30.4%) had multiple other disorders. Although the response rate to paroxetine in the overall population was high (71%), the response rates in patients with comorbid attention deficit hyperactivity disorder, tic disorder, or oppositional defiant disorder (56%, 53%, and 39%, respectively) were significantly less than in patients with OCD only (75%) (intent-to-treat population, last observation carried forward analysis, p < 0.05). Psychiatric comorbidity was associated with a greater rate of relapse in the total patient population (46% for one or more comorbid disorders [p = 0.04] and 56% for two or more comorbid disorders [p < 0.05] vs. 32% for no comorbidity). CONCLUSIONS: The results of these post hoc analyses show that comorbid illness adversely impacted response to pharmacotherapy with paroxetine in pediatric OCD and significantly increased risk of relapse following withdrawal from treatment. Continued paroxetine treatment reduced the relapse rates in all groups compared with placebo, including those with comorbid illness. Because pediatric OCD is frequently comorbid with other psychiatric disorders, results of randomized, controlled pediatric OCD trials that use multiple exclusion criteria may not generalize to more naturalistic OCD samples.

Adolescent↗
PubMed2003

A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors.

OBJECTIVE: Despite a rapidly growing literature on the efficacy of the selective serotonin reuptake inhibitors (SSRI) in the treatment of juvenile psychiatric disorders, relatively little is described about emotional, behavioral, and cognitive adverse effects associated with their use. To this end we completed a retrospective analysis of medical charts to determine the incidence, nature, and clinical correlates of treatment emergent adverse effects in the behavioral, cognitive, and emotional domains. METHODS: We systematically evaluated the medical charts of children treated with SSRI for depressive or obsessive-compulsive disorders for a mean (+/- SD) of 26.9 + 20.8 months to determine the incidence, nature, and clinical correlates of treatment emergent psychiatric adverse events (PAE). Charts were reviewed for diagnoses, type and dose of SSRI and adjunct medication, specific type of PAE, and time to onset and offset of PAE. RESULTS: In total, 82 charts of children and adolescents (mean age 12.2 +/- 3.2 years) were examined. PAE occurred in 22% of children and were most commonly related to disturbances in mood. PAE were not associated with psychiatric diagnosis(es), age, sex, concurrent medications, doses or specific serotonin reuptake inhibitors. The onset of PAE was observed typically 3 months after SSRI exposure (median = 91 days). Although PAE diminished with SSRI discontinuation, those that emerged early in treatment diminished significantly more rapidly than those that emerged later (median offset was 10 and 49 days, respectively). Re-exposure to an SSRI resulted in another PAE in 44% (n = 18) of the group. CONCLUSION: Based on the retrospective review of medical charts, youth receiving SSRI appear to be at risk for treatment emergent PAE and recurrence with re-exposure to an SSRI. Prospective longer term studies evaluating the course and prognosis of youths manifesting PAE to SSRI are necessary.

Adolescent↗
PubMed2003

Defining a developmental subtype of bipolar disorder in a sample of nonreferred adults by age at onset.

OBJECTIVE: To test the hypothesis that the age at onset of bipolar disorder would identify a developmental subtype of bipolar disorder in adults characterized by increased levels of irritability, chronic course, rapid cycling, and comorbidity with attention deficit hyperactivity disorder. METHODS: Forty-four adult subjects diagnosed with bipolar disorder were selected from large family studies of youth with and without attention deficit hyperactivity disorder. These subjects were stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%), adolescence (13-18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24, 55%). All subjects were administered structure diagnostic interviews and a brief cognitive battery. RESULTS: In contrast with adult-onset bipolar disorder, child-onset bipolar disorder was associated with a longer duration of illness, more irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling course, and increased comorbidity with childhood disruptive behavior disorders and anxiety disorders. CONCLUSION: Stratification by age at onset of bipolar disorder identified subgroups of adult subjects with differing clinical correlates. This pattern of correlates is consistent with findings documented in children with pediatric bipolar disorder and supports the hypothesis that child-onset bipolar disorder may represent a developmental subtype of the disorder.

Adolescent↗
PubMed2003

Patterns of comorbidity and dysfunction in clinically referred preschool and school-age children with bipolar disorder.

OBJECTIVE: Despite its common onset in preschool years, few studies have examined the characteristics of bipolar disorder (BPD) in preschoolers. This study reports on the clinical characteristics, psychiatric comorbidity, and functioning of preschoolers identified with BPD who were referred to a pediatric psychiatric clinic. METHODS: Structured psychiatric interviews assessing lifetime psychopathology by Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) criteria were completed with parents about their children and confirmed by clinical interview of the child. Family, social, and overall functioning were also assessed at intake. Findings from preschoolers ages 4 to 6 years were compared with a group of children ages 7 to 9 years (school age). RESULTS: We identified 44 preschoolers and 29 consecutively ascertained school-age youth with BPD. Preschoolers had similar rates of comorbid psychopathology compared to school-age youth with BPD. Preschoolers and school-age children with BPD typically manifest symptoms of mania and major depression simultaneously (mixed states). Both preschoolers and school-age children had substantial impairment in school, social, and overall functioning. CONCLUSIONS: These results suggest that clinically referred preschoolers with BPD share with school-age children with BPD high rates of comorbid psychopathology and impaired functioning. Follow-up of these clinically referred preschoolers with BPD evaluating the stability of their diagnoses, treatment response, and their long-term outcome is necessary.

Aging↗
PubMed2003

Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall.

OBJECTIVE: To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XR), in pediatric attention-deficit/hyperactivity disorder (ADHD). METHOD: Fifty-one children (aged 6-12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo. RESULTS: PK parameters evidenced substantial intersubject variability (coefficients of variation = 28-56%). Time to maximum concentration (Tmax) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine (t = -2.35, p = .04, df = 8.6) and 3.2 hours for levoamphetamine (t = -2.39, p = .04, df = 9.2). The d- and l-isomer concentrations were highly correlated and approximated a 3:1 ratio. CONCLUSIONS: SLI381 showed extended Tmax values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration.

Amphetamines↗
PubMed2003

Analog classroom assessment of a once-daily mixed amphetamine formulation, SLI381 (Adderall XR), in children with ADHD.

OBJECTIVES: This investigation was conducted primarily to assess the safety and efficacy of SLI381 (Adderall XR), developed as a once-daily treatment for children with attention-deficit/hyperactivity disorder (ADHD). Secondary objectives included examination of the time course, pharmacokinetic, and pharmacodynamic properties of SLI381. METHOD: This was a randomized, double-blind, crossover study of three doses of SLI381 (10, 20, and 30 mg), placebo, and an active control (Adderall 10 mg) given once daily to 51 children with ADHD. Weekly assessments in an analog classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained every 1.5 hours over a 12-hour period. RESULTS: SLI381 was well tolerated. All active treatment conditions displayed significant time course effects and were superior to placebo in improving efficacy measures. Dose-dependent improvements were evident for SLI381. SLI381 20 and 30 mg and Adderall all showed rapid improvements by 1.5 hours, but only the SLI381 20- and 30-mg doses showed continued activity at 10.5 and 12 hours for classroom behavior and math test performance versus placebo. CONCLUSIONS: These data provide support for the benefit of this novel, once-daily amphetamine preparation in the treatment of ADHD. The longer duration of action of SLI381 has the potential to simplify psychostimulant dosing, thus reducing dose diversion and eliminating the need for in-school administration. SLI381 appears to be a useful treatment option for many children with ADHD.

Amphetamines↗
PubMed2003

Diagnostic threshold for conduct disorder in girls and boys.

Concerns about gender bias in the diagnostic criteria for conduct disorder (CD) have prompted some researchers to recommend that the diagnostic threshold in girls be lowered. Since CD is a highly familial condition, the authors assessed the diagnostic validity of subthreshold CD in girls using family study methodology. They compared the rates of antisocial disorders (CD and antisocial personality disorder) in relatives of four groups of index children: children with attention deficit hyperactivity disorder (ADHD) and full, subthreshold, or no CD diagnoses and non-ADHD/non-CD control subjects. Results showed no interaction between gender and familiality across the four groups. Furthermore, there was no significant evidence of familiality of subthreshold CD. From a family genetic perspective, the diagnostic threshold for CD does not appear to differ by gender. The current results support the possibility that differential rates of CD reflect actual differences in rates of antisocial behavior across gender.

Antisocial Personality Disorder↗