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J Biederman

Publications and source records attributed to J Biederman.

At least 55 records · Page 3Linked to original sources
PubMed2001

Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder.

OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component. Although several studies have shown an association between ADHD and the 7-repeat allele of the dopamine D(4) receptor gene (DRD4), several studies have not. Thus, the status of the ADHD-DRD4 association is uncertain. METHOD: Meta-analysis was applied to case-control and family-based studies of the association between ADHD and DRD4 to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. RESULTS: For both the case-control and family-based studies, the authors found 1) support for the association between ADHD and DRD4, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias. CONCLUSIONS: Although the association between ADHD and DRD4 is small, these results suggest that it is real. Further studies are needed to clarify what variant of DRD4 (or some nearby gene) accounts for this association.

Adolescent↗
PubMed2001

School dropout and conduct disorder in Brazilian elementary school students.

OBJECTIVES: To evaluate the association between DSM-IV conduct disorder (CD) and school dropout in a sample of students from the third and fourth elementary grades at state schools in the capital of the southernmost state of Brazil. METHODS: In this case-control study, students that dropped out of schools (n = 44) and a control group who continued attending schools (n = 44) were assessed for CD and other prevalent mental disorders, using the Schedule for Affective Disorders and Schizophrenia for School Age Children, Epidemiological Version (K-SADS-E). RESULTS: The prevalence of DSM-IV CD was significantly higher in the school-dropout group than in control subjects (P < 0.001), both in the entire sample and in a subsample including only subjects under age 12 years (P = 0.001). Also, the odds ratio (OR) for school dropout was significantly higher in the presence of DSM-IV CD, even after controlling for potential confounding factors (age, estimated IQ, school repetition, family structure, and income) (P < 0.01). CONCLUSION: Our results extend to children and young adolescents previous findings from studies of older adolescents, suggesting an association between school dropout and CD.

Adolescent↗
PubMed2001

Long-term stability of the Child Behavior Checklist in a clinical sample of youth with attention deficit hyperactivity disorder.

Evaluated the long-term stability of the Child Behavior Checklist (CBCL) in a longitudinal clinical sample of youth with attention deficit hyperactivity disorder (ADHD), testing the hypothesis that the CBCL scales will show stability over time. Participants were 105 Caucasian, non-Hispanic boys with ADHD between the ages of 6 and 17 assessed at baseline and at a 4-year follow-up. Stability of CBCL scales were computed for dimensional (intraclass correlation coefficients [ICCs], Pearson correlations) and dichotomized scale scores (kappa coefficients and odds ratios [ORs]). Evidence was found for stability of the categorical and dimensional types of scores, as demonstrated by statistically significant stability of the Pearson correlation coefficients, kappas, and ORs. The robust findings obtained from ICCs and kappa coefficients document substantial stability for CBCL scales over time within individuals with ADHD. These results support the informativeness of the CBCL as a useful measure of longitudinal course in clinical samples of youth with ADHD.

Adolescent↗
PubMed2001

Diagnostic and therapeutic dilemmas in the management of pediatric-onset bipolar disorder.

Although the diagnosis of pediatric-onset bipolar disorder is controversial, an increasing literature of systematic research has challenged the traditional view that this disorder is a rare condition. This article summarizes research regarding the atypical presentation of pediatric bipolar disorder and its overlap with attention-deficit/hyperactivity disorder and other comorbid conditions, as well as family-genetic and treatment data. When structured interview data were examined, cases of pediatric mania constituted 16% of referrals to our outpatient clinic. Presentation is atypical by adult standards and includes irritability, chronicity, and mixed state. Family-genetic and treatment data help to establish diagnostic validity. Pediatric bipolar disorder is not a rare condition. Treatment requires a combined pharmacotherapy approach to address issues of comorbidity. Atypical antipsychotic medications have provided promising treatment results, but additional controlled clinical trials are needed.

Adolescent↗
PubMed2000

Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis.

BACKGROUND: Bipolar disorder has emerged as a risk factor for substance use disorders (alcohol or drug abuse or dependence) in youth; however, the association between bipolar disorder and substance use disorders is complicated by comorbidity with conduct disorder. We used familial risk analysis to disentangle the association between the three disorders. METHODS: We compared relatives of four proband groups: 1) conduct disorder + bipolar disorder, 2) bipolar disorder without conduct disorder, 3) conduct disorder without bipolar disorder, and 4) control subjects without bipolar disorder or conduct disorder. All subjects were evaluated with structured diagnostic interviews. For the analysis of substance use disorders, Cox proportional hazard survival models were utilized to compare age-at-onset distributions. RESULTS: Bipolar disorder in probands was a risk factor for both drug and alcohol addiction in relatives, independent of conduct disorder in probands, which was a risk factor for alcohol dependence in relatives independent of bipolar disorder in probands, but not for drug dependence. The effects of bipolar disorder and conduct disorder in probands combined additively to predict the risk for substance use disorders in relatives. CONCLUSIONS: The combination of conduct disorder + bipolar disorder in youth predicts especially high rates of substance use disorders in relatives. These findings support previous results documenting that when bipolar disorder and conduct disorder occur comorbidly, both are validly diagnosed disorders.

Adolescent↗
PubMed2000

Pediatric mania: a developmental subtype of bipolar disorder?

Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards.

Adolescent↗
PubMed2000

Attention-deficit disorder and conduct disorder in girls: evidence for a familial subtype.

BACKGROUND: The frequent comorbidity between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) raises the possibility that ADHD+CD is a distinct and separate condition. METHODS: We tested hypotheses about patterns of familial association between ADHD, CD, oppositional defiant disorder (ODD) and adult antisocial personality disorder (ASPD). Using family study methodology in a sample of girls, we found 11 children with diagnoses of ADHD+ CD, 39 with ADHD+ODD, and 90 with ADHD only. These were compared with 122 non-ADHD, non-CD control probands. Familial risk analysis was utilized. RESULTS: Relatives of each ADHD proband subgroup were at significantly greater risk for ADHD, and the relatives of ADHD-only subjects were at a greater risk of ODD than relatives of control subjects. Also, rates of CD were elevated among relatives of ADHD+CD probands only, and the coaggregation of ADHD and the antisocial disorders could not be accounted for by marriages between ADHD and antisocial spouses. Both ADHD and antisocial disorders occurred in the same relatives more often than expected by chance. CONCLUSIONS: These findings suggest that ADHD with and without antisocial disorders may be etiologically distinct disorders and provide evidence for the nosologic validity of ICD-10 hyperkinetic conduct disorder.

Adolescent↗
PubMed2000

Attention-deficit/hyperactivity disorder in adults: an overview.

To assess the validity of adult attention-deficit/hyperactivity disorder (ADHD), we reviewed clinical, family, psychopharmacologic, neurobiological, and outcome studies. We found multiple reports describing adults with clinical features highly reminiscent of the childhood ADHD. These adults, who are impulsive, inattentive, and restless, have the clinical "look and feel" of ADHD children. As with their childhood counterparts, many adults with ADHD suffer from antisocial, depressive, and anxiety disorders. They also show clinically significant impairments--histories of school failure, occupational problems, and traffic accidents. Studies of biological features show correspondences between child and adult cases of ADHD. Both show familial aggregation and a characteristic profile of neuropsychologic deficits; an emerging neuroimaging literature suggests that abnormalities in the same brain regions underlie both the child and adult forms of the disorder. Although these converging lines of evidence support the validity of ADHD in adults, follow-up studies of ADHD children have yielded ambiguous results. This ambiguity is in part due to differences in how researchers define the persistence of ADHD, a problem that suggests future research focus on how best to diagnose ADHD in adulthood.

Adult↗
PubMed2000

Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder.

Converging evidence from family, twin, and adoption studies points to a substantial genetic component of the etiology of attention deficit hyperactivity disorder (ADHD). These data about ADHD have motivated molecular genetic studies of the disorder, which have produced intriguing but somewhat conflicting results. Some studies have reported associations with candidate genes and others not. Our review of the literature shows that one problem facing molecular genetic studies of ADHD is that its recurrence risk to first-degree relatives is only about five times higher than the population prevalence. This suggests that, to produce consistently replicated results, molecular genetic studies should either use much larger samples or should select those families in which genes exert the largest effect. Risch [(1990a) Am J Hum Genet 46:222-228; (1990b) Am J Hum Genet 46:229-241] proved that the statistical power of a linkage study increases with the magnitude of risk ratios (lambda's) computed by dividing the affection rate among each relative type to the rate of affection in the population. Our prior work suggests two dimensions of genetic heterogeneity that might be useful for selecting ADHD subjects for molecular genetic studies: comorbidity with conduct disorder and persistence of ADHD into adolescence. This paper shows that these sub-phenotypes are useful for molecular genetic studies because (1) they have much higher empirical lambda values and (2) they affect a substantial minority of ADHD patients.

Adolescent↗
PubMed2000

Clinical correlates of obsessive compulsive disorder in children and adolescents referred to specialized and non-specialized clinical settings.

The objective of this study was to assess the extent of referral bias by comparing children and adolescents with Obsessive Compulsive Disorder (OCD) ascertained through a specialized pediatric OCD and a general child psychiatry clinic. Subjects were juveniles meeting DSM-III-R and DSM IV criteria for OCD referred to a general pediatric psychopharmacology clinic and to a specialized OCD clinic within the same academic medical center. Subjects were evaluated clinically and with structured diagnostic interviews using the Kiddie SADS-E. OCD was identified in 8.6% of the general psychiatry clinic subjects. The only differences between ascertainment sources in clinical or sociodemographic characteristics of OCD subjects were higher rates of social phobia and ADHD in the non-specialized clinic, while specialty clinic subjects had a greater lifetime severity of OCD and were more likely to have received treatment of their OCD. Because we found limited evidence for referral biases, our results suggest that findings from studies using either of these sources may generalize to the other. It also suggests that pooling subjects from the two sources is justified. Nevertheless, because some group differences did emerge, researchers should acknowledge referral bias as a potential limitation of their work.

Adolescent↗
PubMed2000

Non-stimulant treatments for ADHD.

We reviewed the literature of medication trials in ADHD to evaluate the scope of the available non-stimulant treatments. A variety of compounds with a common noradrenergic/ dopaminergic activity have shown documented anti-ADHD activity. There is a substantial body of literature documenting the efficacy of tricyclic antidepressants on ADHD in over 1,000 subjects. In addition, the atypical antidepressant bupropion and the novel noradrenergic specific antidepressant tomoxetine have also been documented to be effective in the treatment of ADHD in controlled clinical trials. Despite wide use, the scientific base supporting the efficacy of alpha-2, noradrenergic agonists continues to be limited. Several lines of evidence provide preliminary support for the potential benefits of cholinergic cognitive enhancing drugs in such as anticholinesterase inhibitors (tacrine, donepezil) as well as novel nicotinic analogues (ABT-418). Despite these promising results, more research is needed on alternative pharmacologic treatments for the treatment of ADHD.

Adolescent↗
PubMed2000

Exploring ADHD age-of-onset criterion in Brazilian adolescents.

OBJECTIVE: To explore age-of-onset criterion for the diagnosis of attention-deficit hyperactivity disorder (ADHD) in a school sample of young Brazilian adolescents. METHODS: 191 students aged 12 to 14 years were evaluated using DSM-IV ADHD criteria, measures of ADHD symptoms and global impairment. RESULTS: Both adolescents with ADHD (n = 30) and adolescents who fulfilled all DSM-IV ADHD criteria, except age of onset of impairment criterion (ADHD w/o age-of-onset, n = 27) had significantly higher scores on Attention Problems, Delinquent and Aggressive Behavior scales of the Child Behavior Checklist (CBCL) and lower scores on the Child Global Assessment scale (CGAS) than non-ADHD adolescents (n = 134). Adolescents with ADHD and youths with ADHD w/o age-of-onset did not differ significantly in any measure assessed. CONCLUSION: These results concur with recent literature proposing revision of the age-of-onset criterion for the diagnosis of ADHD.

Adolescent↗
PubMed2000

Is bipolar disorder a risk for cigarette smoking in ADHD youth?

Despite emerging literature linking juvenile bipolar disorder (BPD) and substance abuse, little is known about a link between BPD and cigarette smoking. To this end, we evaluated the association between BPD and cigarette smoking in youth. Subjects were 31 bipolar adolescents derived from a cohort of boys with DSM-III-R ADHD (N = 128) and non-ADHD comparisons (N = 109) followed prospectively for 4 years into mid-adolescence. Information on cigarette smoking was obtained in a standardized manner blind to the proband's clinical status. Logistic regression models were used to determine risk for smoking at follow-up. BPD was associated with a higher risk for cigarette smoking in mid-adolescence, which was largely accounted for by conduct disorder. The developmental onset of BPD in adolescence (age 13-18 years) conferred a greater risk for cigarette smoking compared to those youths with the onset of their BPD prepubertally (< or = 12 years; odds ratio = 10.8, p < 0.01), even after controlling for conduct disorder and other confounds. The naturalistic treatment of BPD with combined counseling and pharmacotherapy appeared to reduce the risk for cigarette smoking. BPD, particularly when it onsets in adolescence, is a significant risk factor for the early initiation of cigarette smoking in these ADHD youths. These data coupled with the literature strongly suggest that juveniles with BPD need to be carefully monitored for the early initiation of cigarette smoking and substance abuse.

Adolescent↗
PubMed2000

Family-based tests of association and linkage that use unaffected sibs, covariates, and interactions.

We extend the methodology for family-based tests of association and linkage to allow for both variation in the phenotypes of subjects and incorporation of covariates into general-score tests of association. We use standard association models for a phenotype and any number of predictors. We then construct a score statistic, using likelihoods for the distribution of phenotype, given genotype. The distribution of the score is computed as a function of offspring genotypes, conditional on parental genotypes and trait values for offspring and parents. This approach provides a natural extension of the transmission/disequilibrium test to any phenotype and to multiple genes or environmental factors and allows the study of gene-gene and gene-environment interaction. When the trait varies among subjects or when covariates are included in the association model, the score statistic depends on one or more nuisance parameters. We suggest two approaches for obtaining parameter estimates: (1) choosing the estimate that minimizes the variance of the test statistic and (2) maximizing the statistic over a nuisance parameter and using a corrected P value. We apply our methods to a sample of families with attention-deficit/hyperactivity disorder and provide examples of how covariates and gene-environment and gene-gene interactions can be incorporated.

Alleles↗
PubMed2000

Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young.

Pediatric bipolar disorder is commonly mixed with co-occurring symptoms of major depression and mania. Knowledge has begun to accumulate on the treatment of the mania component, but limited information is available to guide the therapeutic approach to bipolar depression. To this end, we reviewed the medical charts of 59 patients with diagnosis of DSM-III-R bipolar disorder from an outpatient pediatric psychopharmacology clinic. Multivariate methods were used to model the probability of improvement and relapse at each visit of clinical follow-up. Serotonin-specific antidepressants were significantly associated with both an increased rate of improvement of bipolar depression-relative risk = 6.7 (1.9-23.6); p = 0.003-and a significantly greater probability of relapse of manic symptomatology-relative risk = 3.0 (1.2-7.8); p = 0.02. Although mood stabilizers improved manic symptomatology, they had no demonstrable effect on the symptoms of bipolar depression. Despite the increased risk of mood destabilization, serotonin-specific antidepressants did not interfere with the antimanic effects of mood stabilizers. Because bipolar youth commonly come to clinical practice with depression, these results underscore the importance of assessing a lifetime history of bipolar disorder in making treatment decisions in depressed youth.

Adolescent↗
PubMed2000

A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder.

OBJECTIVES: To study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD). METHODOLOGY: Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responders to treatment were then randomized into a 3-week, controlled discontinuation phase. During this phase, subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depression. RESULTS: Of the 35 subjects enrolled in the study, 32 completed the open phase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusion of the open 6-week study, NT was related to a significant reduction in ADHD (p < 0.001) and oppositional symptoms (p < 0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects randomized to placebo (31 versus 21; t = 2.2; p < 0.04). No significant adverse events were observed, and children were noted to have weight gain during the trial. CONCLUSIONS: These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality. This group of children and adolescents tolerated robust dosing of NT well, with few clinical or cardiovascular adverse events.

Adolescent↗
PubMed2000

Pemoline treatment of adolescents with attention deficit hyperactivity disorder: a short-term controlled trial.

BACKGROUND: Despite the increased recognition of attention deficit hyperactivity disorder (ADHD) in adolescents, few controlled studies have assessed treatments for this age group. Adolescent issues, such as embarrassment at receiving medication at school and experimentation with abusable substances, have accelerated efforts to find effective, well-tolerated treatments beyond traditional stimulants. Pemoline has been found effective for treating both children and adults with ADHD but has not been evaluated in adolescents with ADHD. METHODS: Twenty-one adolescents (mean age 14 years old) diagnosed with ADHD by structured and clinical interviews participated in a 10-week, double-blind crossover design study of pemoline. Dosing was optimized with robust doses up to 3 mg/kg/day in one to two doses. Clinical evaluations of ADHD, depression, anxiety, and oppositional defiant disorder (ODD) symptoms were assessed weekly. RESULTS: Adolescents with ADHD exhibited a marked response to pemoline treatment relative to placebo on the ADHD rating scale (p = 0.001), with an average reduction of 3.02 points per week of treatment. Sixty percent of adolescents responded to pemoline, compared to 11% treated with placebo. This response was independent of gender or lifetime psychiatric comorbidity. Pemoline was well tolerated, with patients averaging 2.88 mg/kg/day in two doses per day, with a mean dose at end of follow-up of 181.1 mg (SD 45.6, range 112.5-262.5 mg). Side effects were mild, and no adverse hepatic events occurred. CONCLUSIONS: These findings resemble those reported in children and adults with ADHD. This trial suggests pemoline is well tolerated and effective in adolescents and may be a particularly useful ADHD treatment for adolescents.

Adolescent↗