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J Biederman

Publications and source records attributed to J Biederman.

At least 91 records · Page 5Linked to original sources
PubMed1999

Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder.

This review revisits the thesis that a dysregulation of the central noradrenergic networks may underlie the pathophysiology of ADHD. We review the pertinent neurobiological and pharmacological literature on ADHD. The noradrenergic system has been intimately associated with the modulation of higher cortical functions including attention, alertness, vigilance and executive function. Noradrenergic activation is known to profoundly affect the performance of attention, especially the maintenance of arousal, a cognitive function known to be deficient in ADHD. Data from family, adoption, twin, and segregation analysis strongly support a genetic hypothesis for this disorder. Although molecular genetic studies of ADHD are relatively new and far from definitive, several replicated reports have found associations between ADHD with DAT and D4 receptor genes. Brain imaging studies fit well with the idea that dysfunction in fronto-subcortical pathways occurs in ADHD with its underlying dysregulation of noradrenergic function. A wealth of pharmacological data (within and without the stimulant literature) provides strong evidence for selective clinical activity in ADHD for drugs with noradrenergic and dopaminergic pharmacological profiles. Available research provides compelling theoretic, basic biologic and clinical support for the notion that ADHD is a brain disorder of likely genetic etiology with etiologic and pathophysiologic heterogeneity. Neurobiological and pharmacological data provide compelling support for a noradrenergic hypothesis of ADHD and suggest that drugs with noradrenergic activity may play an important role in the therapeutics of this disorder.

Arousal↗
PubMed1999

Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.

BACKGROUND: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e., focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-deficit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recruit the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. METHODS: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI. RESULTS: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network, indicating ACcd hypoactivity was not caused by globally poor neuronal responsiveness. CONCLUSIONS: The data support a hypothesized dysfunction of the ACcd in ADHD.

Adolescent↗
PubMed1999

Attention-deficit/hyperactivity disorder and comorbidity.

Studies of children with ADHD consistently document high rates of comorbid psychiatric conditions, including conduct disorders, depression and other mood disorders, anxiety disorders, and tic disorders. In diagnosing children with ADHD, one must be careful not to dismiss other symptomatology as secondary. Poor social skills, problems with parents, low academic functioning, and other correlates of ADHD can be construed as causal factors. Although these should not be ignored, neither should the possibility that a child suffers from another psychiatric disorder that might respond to appropriate pharmacotherapy. A variety of behavior rating scales are available to the practitioner as the first steps in this process.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Substance use disorders in high-risk adolescent offspring.

OBJECTIVE: To examine the risk for substance use disorders (SUD) in offspring of SUD parents who were not selected due to referral to SUD treatment centers. METHODS: The original sample was ascertained through two groups of index children: 140 ADHD probands and 120 non-ADHD comparison probands. These groups had 174 and 129 biological siblings and 279 and 240 parents, respectively. RESULTS: We found that: 1) parental SUD was associated with SUD and all SUD subtypes in the offspring; 2) parental alcohol use disorders were associated with alcohol use disorders in the offspring as well as co-occurring alcohol and drug use disorders but not drug use disorders alone in the offspring; and 3) drug use disorders in the parents were associated with drug use disorders but not alcohol use disorders in the offspring. CONCLUSIONS: These findings suggest that alcoholism and drug abuse may breed true from parents to their offspring, but further work with larger samples is needed to confirm this idea. Our findings also suggest a possible common diathesis that is expressed as comorbid alcohol and drug use in the offspring of alcoholic parents. If confirmed, these findings may be useful for the development of preventive and early intervention strategies for adolescents at high risk for SUD based on parental history of SUD.

Adolescent↗
PubMed1999

Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder.

The objective of this study was to evaluate pharmacological approaches for attention deficit hyperactivity disorder (ADHD) in children with bioplar disorder and comorbid ADHD. The medical charts of 38 patients with diagnoses of both Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised ADHD and bipolar disorder were reviewed over multiple visits to assess improvement and prescription patterns. Logistic regression was used to model the probability of improvement at each visit, and robust standard errors were estimated in order to account for correlation among individuals using Huber's correction for clustered data. The proportion of visits at which ADHD symptoms were rated as improved following initial improvement in manic symptoms was 7.5 times greater than before initial improvement of manic symptoms. The recurrence of manic symptoms following their initial stabilization significantly inhibited ADHD response to medication. Although tricyclic antidepressants (TCAs) significantly increased the probability of ADHD improvement following mood stabilization, there was also a significant association between treatment with TCAs and relapse of manic symptoms. Our results support the hypothesis that mood stabilization is a prerequisite for the successful pharmacologic treatment of ADHD in children with both ADHD and manic symptoms. Although TCAs can be helpful in the management of ADHD children with manic symptoms, these drugs should be used with caution since they can also have a destabilizing effect on manic symptoms.

Adolescent↗
PubMed1999

A pilot controlled family study of DSM-III-R and DSM-IV ADHD in African-American children.

BACKGROUND: Very little is known about attention-deficit hyperactivity disorder (ADHD) in African-American children, and although the familial transmission of ADHD has been well established in white samples, prior work has not evaluated this feature of ADHD in African-American families. METHOD: Subjects were 37 first-degree relatives of children with DSM-III-R-defined ADHD and 52 first-degree relatives of non-ADHD comparison children matched for ethnicity, age, and gender. DSM-III-R-based structured interviews (modified to include DSM-IV diagnoses) provided the basis for psychiatric diagnoses in relatives. RESULTS: The risks for both DSM-III-R and DSM-IV ADHD were significantly greater in first-degree relatives of ADHD probands than in relatives of controls. In addition, the relatives of ADHD probands also were at higher risk for oppositional defiant disorder, antisocial personality disorder, major depression, generalized anxiety, and substance use disorders. CONCLUSIONS: These results suggest that ADHD and related disorders are familial in African-Americans. Further work is needed to confirm the familial transmission of ADHD in African-American children and to explore the role of genetics as well as environmental factors in the transmission of the disorder.

Adolescent↗
PubMed1999

Antecedents and complications of trauma in boys with ADHD: findings from a longitudinal study.

OBJECTIVE: To examine the relationship between trauma and attention-deficit hyperactivity disorder (ADHD), evaluating whether ADHD increases the risk for trauma, the risk for posttraumatic stress disorder (PTSD), or the risk for trauma-associated psychopathology. METHOD: Data from a longitudinal sample of 260 children and adolescents with and without ADHD were examined. All were evaluated comprehensively with assessments in multiple domains of functioning including systematic assessments of trauma and PTSD. Comparisons were made between traumatized and nontraumatized youths with and without ADHD. RESULTS: No meaningful differences were detected in comparisons between ADHD and control children, either in the rate of trauma exposure or in the development of PTSD. Although trauma was associated with the development of major depression, this effect was independent of ADHD status. In contrast, bipolar disorder at baseline assessment was a significant risk factor for subsequent trauma exposure. CONCLUSIONS: ADHD was not found to be a risk factor for either trauma exposure or PTSD, but childhood mania was. If confirmed, this finding stresses the potential severe clinical sequelae of childhood mania in children.

Adolescent↗
PubMed1999

Desipramine clearance in children and adolescents: absence of effect of development and gender.

OBJECTIVE: To examine the influence of development and gender on the pharmacokinetics of desipramine (DMI) in the pediatric population. METHOD: DMI pharmacokinetic parameters were calculated from 407 routinely drawn, dose- and weight-normalized serum concentrations in 173 youths receiving DMI (90 children, 83 adolescents; 29 were female, 144 were male). RESULTS: Mean pharmacokinetic parameters for the entire population included dose (3.78 +/- 1.51 mg/kg), weight- and dose-normalized serum concentration (45.41 +/- 47.39 [micrograms/L]/[mg/kg]), and DMI clearance (0.68 +/- 1.51 [L/kg]/hr). No between-group differences for children and adolescents were detected in dose (child, adolescent) (3.73 +/- 1.40 mg/kg, 3.83 +/- 1.68 mg/kg), weight- and dose-normalized serum concentrations (44.52 +/- 39.6 [micrograms/L]/[mg/kg], 46.34 +/- 34.89 [micrograms/L]/[mg/kg]; p = .62), and clearance (0.680 +/- 0.890 [L/kg]/hr, 0.695 +/- 1.05 [L/kg]/hr; p = .103). No between-group gender differences were detected in dose (male, female) (3.83 +/- 1.55 mg, 3.39 +/- 1.84 mg), weight- and dose-normalized serum concentrations (45.15 +/- 37.76 [micrograms/L]/[mg/kg], 47.14 +/- 34.96 [micrograms/L]/mg/kg]; p = .720), and clearance (0.699 +/- 0.89 [L/kg]/hr, 0.606 +/- 0.535 [L/kg]/hr; p = .390). CONCLUSIONS: These results suggest that age and gender do not significantly influence DMI clearance or dose-normalized serum concentrations in the pediatric population.

Adolescent↗
PubMed1999

Further evidence of a bidirectional overlap between juvenile mania and conduct disorder in children.

OBJECTIVE: To investigate systematically the overlap between mania and conduct disorder (CD) in a sample of consecutively referred youths. It was hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the 2 disorders would have correlates of both. METHOD: Subjects were consecutively referred children and adolescents meeting DSM-III-R diagnostic criteria on structured diagnostic interview for CD (n = 116), mania (n = 110), and CD + mania (n = 76). RESULTS: Of 186 children and adolescents with mania and of 192 with CD, 76 satisfied criteria for both CD and mania, representing 40% of youths with CD and 41% of youths with mania, respectively. Examination of the clinical features, patterns of psychiatric comorbidity, and functioning in multiple domains showed that children with CD and mania had similar features of each disorder irrespective of the comorbidity with the other disorder. CONCLUSIONS: The data suggest that when mania and CD co-occur in children, both are correctly diagnosed. In these comorbid cases, CD symptoms should not be viewed as secondary to mania and manic symptoms should not be viewed as secondary to CD.

Adolescent↗
PubMed1999

Multicenter open-label sertraline study in adolescent outpatients with major depression.

OBJECTIVE: The aim of this multicenter outpatient study was to assess the therapeutic benefits, response patterns, and safety of sertraline in adolescent major depressive disorder (MDD). METHOD: Fifty-three adolescent outpatients with MDD were treated in an open-label, 10-week, acute-phase trial with sertraline and, if responders, for an additional 12-week continuation phase. Diagnostic and response assessments included the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), 17-item K-SADS-derived depression severity score, Hamilton Depression Rating Scale, Beck Depression Inventory, and Clinical Global Impression Scale. RESULTS: By 2 weeks, when analyzed as continuous variables, all severity scores showed significant differences from baseline. This pattern persisted through 10 weeks, with a significantly greater response occurring when treatment was extended from 6 to 10 weeks. Both clinician- and patient-rated improvement was maintained during continuation treatment. Response rates varied considerably when depression rating scales were analyzed categorically. Sertraline was generally well tolerated and did not induce manic symptoms. CONCLUSIONS: In open treatment of adolescent MDD with sertraline, significant improvement occurred early on and was maintained for 22 weeks. Absolute response rates varied depending on the rating scales used, definition of response, and length of treatment. Maximal response rates were obtained by clinician-defined ratings after 10 weeks of treatment.

Adolescent↗
PubMed1999

Absence of cardiovascular adverse effects of sertraline in children and adolescents.

OBJECTIVE: In a 12 week, placebo-controlled, parallel-design, multicenter study of sertraline for obsessive-compulsive disorder in 107 children and 80 adolescents, the authors prospectively assessed cardiovascular effects to doses of sertraline of < or = 200 mg/day. METHOD: Vital signs (blood pressure and heart rate) and electrocardiograph parameters (ECGs) were systematically evaluated at baseline and again throughout treatment. RESULTS: There were no clinically significant cardiovascular adverse events in any of the subjects enrolled in the study. Moreover, compared with baseline and placebo, sertraline treatment at an average dose of 167 mg did not result in any clinically meaningful changes in any ECG indices (PR, QRS, and QTc intervals), cardiac rhythm, blood pressure, or heart rate. CONCLUSIONS: These prospectively derived results support the cardiovascular safety of sertraline at doses up to 200 mg in children and adolescents.

Adolescent↗
PubMed1999

Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder.

OBJECTIVE: Previous work in adults has suggested that early-onset bipolar disorder (BPD) is associated with an elevated risk for substance use disorders (SUD). To this end, the authors assessed the risk for SUD in child- versus adolescent-onset BPD with attention to comorbid psychopathology. METHOD: All youths (aged 13-18 years) with available structured psychiatric interviews were studied systematically. From clinic subjects (N = 333), 86 subjects with DSM-III-R BPD were identified. To evaluate the risk for SUD and BPD while attending to developmental issues, the authors stratified the BPD sample into those with child-onset BPD (< or = 12 years of age, n = 50) and those with adolescent-onset BPD (13-18 years of age, n = 36). RESULTS: In mid-adolescence, youths with adolescent-onset BPD were at significantly increased risk for SUD relative to those with child-onset BPD (39% versus 8%; p = .001). Compared with those with child-onset BPD, those with adolescent-onset BPD had 8.8 times the risk for SUD (95% confidence interval = 2.2-34.7; chi 7(2) = 9.7, p = .002). The presence of conduct disorder or other comorbid psychopathology within BPD did not account for the risk for SUD. CONCLUSIONS: Adolescent-onset BPD is associated with a much higher risk for SUD than child-onset BPD, which was not accounted for by conduct disorder or other comorbid psychopathology. Youths with adolescent-onset BPD should be monitored and educated about SUD risk. The identification and treatment of manic symptomatology may offer therapeutic opportunities to decrease the risk for SUD in these high-risk youths.

Adolescent↗
PubMed1999

ADHD in a school sample of Brazilian adolescents: a study of prevalence, comorbid conditions, and impairments.

OBJECTIVE: To evaluate the prevalence, comorbid conditions, and impairments of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Porto Alegre, Brazil. METHOD: 1,013 students aged 12 to 14 years were evaluated at 64 state schools, using a screening instrument based on the 18 DSM-IV ADHD symptoms. All positive screened students (n = 99) and a random subset of negative screened subjects (n = 92) had a psychiatric evaluation carried out within a hospital setting or at home. RESULTS: The prevalence of ADHD was estimated to be 5.8% (95% confidence interval = 3.2-10.6), and the comorbidity with other disruptive behavior disorders was high (47.8%). Youths with ADHD (n = 23) had significantly higher rates of school repetitions, suspensions, and expulsions (p < .01) than controls (n = 168). No association was identified between ADHD and alcohol, marijuana, and inhalant use. CONCLUSION: The results extend to adolescents well-documented findings in children, indicating that ADHD is quite prevalent in early adolescence and affected youths are at high risk for impairment and dysfunction in multiple domains.

Adolescent↗
PubMed1999

Risperidone treatment for juvenile bipolar disorder: a retrospective chart review.

OBJECTIVE: To investigate the effectiveness and tolerability of the atypical neuroleptic risperidone in the treatment of juvenile mania. METHOD: This is a retrospective chart review of outpatients with the diagnosis of bipolar disorder (DSM-IV) treated with risperidone at a university center. Response to treatment was evaluated using the Clinical Global Impression Scale (CGI) with separate assessments of mania, psychosis, aggression, and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Twenty-eight youths (mean +/- SD age, 10.4 +/- 3.8 years) with bipolar disorder (25 mixed and 3 hypomanic) who had been treated with risperidone were identified. These children received a mean dose of 1.7 +/- 1.3 mg over an average period of 6.1 +/- 8.5 months. Using a CGI Improvement score of < or = 2 (very much/much improved) to define robust improvement, 82% showed improvement in both their manic and aggressive symptoms, 69% in psychotic symptoms, but only 8% in ADHD symptoms. CONCLUSIONS: Although limited by its retrospective nature, this study suggests that risperidone may be effective in the treatment of manic young people and indicates the need for controlled clinical trials of risperidone and other atypical neuroleptics in juvenile mania.

Adolescent↗
PubMed1999

Clinical correlates of ADHD in females: findings from a large group of girls ascertained from pediatric and psychiatric referral sources.

OBJECTIVE: The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. METHOD: Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. RESULTS: Compared with female controls, girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. CONCLUSIONS: These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females.

Adolescent↗
PubMed1999

Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder.

Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, we tested its efficacy in adults with ADHD using higher daily doses than those previously studied. We conducted a 10-week, double-blind, placebo-controlled, crossover design study of pemoline at a target daily dose of 3 mg/kg per day in 35 adult patients with DSM-III-R and -IV ADHD. We used standardized structured psychiatric instruments for diagnosis. To measure improvement, we used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. ADHD outcome was determined using the ADHD symptom checklist and Clinical Global Impression scales of Severity and Improvement. Of the 35 adults with ADHD who were randomized in the trial, 27 (77%) completed the protocol. Treatment with pemoline in the final week of the 4-week active phase was best tolerated at doses substantially lower than the target dose of 3 mg/kg per day (mean dose, 2.2 mg/kg per day; mean+/-SD, 148+/-95 mg). Pemoline was significantly better at reducing ADHD symptoms compared with placebo (z = 2.4,p < 0.02). Using a predefined 30% reduction in symptoms as an indication of improvement, 50% of pemoline-treated subjects and 17% of subjects in the placebo group were considered positive responders (chi2 = 7.1, p = 0.008). These results indicate that pemoline is moderately effective in the treatment of ADHD in adults. Although robust doses were targeted, most adults preferred more moderate dosing (120-160 mg/day). Given the limited efficacy, tolerability, and concerns of hepatic dysfunction, pemoline should be considered as second-line medication for treating ADHD in adults.

Adult↗
PubMed1999

A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder.

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials. Recent reports have suggested the potential usefulness of cholinergic agents for ADHD. To this end, the authors completed a controlled study of ABT-418, a novel cholinergic activating agent, for the treatment of adults with ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, crossover trial that compared a transdermal patch of ABT-418 (75 mg/day) to placebo in adults who met DSM-IV criteria for ADHD. There were two 3-week treatment periods separated by 1 week of washout. RESULTS: Of the 32 subjects enrolled in the study (88% were men; mean age = 40 years, SD = 9), 29 completed the study. At the endpoint of each active arm (last observation carried forward), a significantly higher proportion of subjects was considered improved while receiving ABT-418 than while receiving placebo (40% versus 13%). Similarly, at endpoint there was a significantly greater reduction in ADHD symptom checklist scores (28% versus 15%). Symptoms reflective of attention, and subjects with less severe ADHD, responded more robustly to ABT-418. Treatment with ABT-418 was relatively well tolerated; dizziness and nausea were the most frequently reported adverse effects. CONCLUSIONS: The results of this investigation indicate that ABT-418, a nicotinic analog, may be a potentially useful agent for the treatment of ADHD.

Administration, Cutaneous↗