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Biomedical subjects

J Biederman

Publications and source records attributed to J Biederman.

At least 109 records · Page 6Linked to original sources
PubMed1999

Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder.

OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some studies have reported an association between ADHD and the dopamine D4 (DRD4) gene. METHOD: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. RESULTS: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat alleles predicted the diagnosis of ADHD. CONCLUSIONS: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.

Adult↗
PubMed1999

Further validation of social impairment as a predictor of substance use disorders: findings from a sample of siblings of boys with and without ADHD.

Examined predictors of substance use disorders in nonreferred siblings of boys with and without attention deficit hyperactivity disorder to further investigate whether previous findings documenting the role of social impairment in predicting substance use disorders would be replicated. Participants were comprehensively assessed at Time 1 and at 4-year follow-up. We found that social impairment was the sole significant predictor of alcohol and substance abuse and smoking after controlling for other variables previously shown to be predictors of substance use disorders. These results confirmed prior findings documenting the critical role of social impairment in predicting later substance use disorders.

Adolescent↗
PubMed1999

Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder.

OBJECTIVE: To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD). METHODS: The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects. RESULTS: Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 [1.8-21.6]). Subjects with ADHD medicated at baseline were at a significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 [0.04-0.6]). For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category. CONCLUSIONS: Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth.

Adolescent↗
PubMed1999

Absence of effect of stimulants on the phamacokinetics of desipramine in children.

We conducted a retrospective chart review to examine the pharmacokinetic interaction between desipramine and the stimulants methylphenidate and dexedrine using routinely monitored desipramine serum concentrations in children receiving desipramine either alone or with a stimulant. Subjects were 142 children and adolescents (age 6-17 yrs; 113 taking desipramine, 29 taking desipramine-stimulants) in whom 401 dose- and weight-normalized serum concentrations were evaluated (333 desipramine, 68 desipramine-stimulants). Desipramine pharmacokinetic parameters were similar for both groups, including mean weight-corrected dose (3.66+/-1.36 mg/kg, desipramine; 3.66+/-1.09 mg/kg, desipramine-stimulants; p=0.97), weight- and dose-normalized serum concentrations (47.26+/-39.26 [microg/L]/[mg/kg], desipramine, 39.02+/-19.92 [microg/L]/[mg/kg], desipramine-stimulants; p=0.09), and clearance (0.690+/-0.913 [L/kg]/hr, desipramine; 0.613+/-0.514 [L/kg]/hr, desipramine-stimulants; p=0.499). When stratified by age, gender, and type of stimulant, no difference was detected (p>0.05) between groups. Our findings indicate the absence of a clinically significant interaction between desipramine and stimulants.

Adolescent↗
PubMed1998

Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial.

CONTEXT: The serotonin reuptake inhibitors are the treatment of choice for patients with obsessive-compulsive disorder; however, empirical support for this assertion has been weaker for children and adolescents than for adults. OBJECTIVE: To evaluate the safety and efficacy of the selective serotonin reuptake inhibitor sertraline hydrochloride in children and adolescents with obsessive-compulsive disorder. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: One hundred eighty-seven patients: 107 children aged 6 to 12 years and 80 adolescents aged 13 to 17 years randomized to receive either sertraline (53 children, 39 adolescents) or placebo (54 children, 41 adolescents). SETTING: Twelve US academic and community clinics with experience conducting randomized controlled trials. INTERVENTION: Sertraline hydrochloride was titrated to a maximum of 200 mg/d during the first 4 weeks of double-blind therapy, after which patients continued to receive this dosage of medication for 8 more weeks. Control patients received placebo. MAIN OUTCOME MEASURES: The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH GOCS), and the NIMH Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) rating scales. RESULTS: In intent-to-treat analyses, patients treated with sertraline showed significantly greater improvement than did placebo-treated patients on the CY-BOCS (adjusted mean, -6.8vs -3.4, respectively; P=.005), the NIMH GOCS (-2.2 vs -1.3, respectively; P=.02), and the CGI-I (2.7 vs 3.3, respectively; P=.002) scales. Significant differences in efficacy between sertraline and placebo emerged at week 3 and persisted for the duration of the study. Based on CGI-I ratings at end point, 42% of patients receiving sertraline and 26% of patients receiving placebo were very much or much improved. Neither age nor sex predicted response to treatment. The incidence of insomnia, nausea, agitation, and tremor were significantly greater in patients receiving sertraline; 12 (13%) of 92 sertraline-treated patients and 3 (3.2%) of 95 placebo-treated patients discontinued prematurely because of adverse medical events (P=.02). No clinically meaningful abnormalities were apparent on vital sign determinations, laboratory findings, or electrocardiographic measurements. CONCLUSION: Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder.

Adolescent↗
PubMed1998

Neurobiology of attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is an early-onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. Family, twin, adoption, segregation analysis, and molecular genetic studies show that is has a substantial genetic component. Although their results are still tentative, molecular genetic studies suggest that three genes may increase the susceptibility to ADHD: the D4 dopamine receptor gene, the dopamine transporter gene, and the D2 dopamine receptor gene. Studies of environmental adversity have implicated pregnancy and delivery complications, marital distress, family dysfunction, and low social class. The pattern of neuropsychological deficits found in ADHD children implicate executive functions and working memory; this pattern is similar to what has been found among adults with frontal lobe damage, which suggests that the frontal cortex or regions projecting to the frontal cortex are dysfunctional in at least some ADHD children. Moreover, neuroimaging studies implicate frontosubcortical pathways in ADHD. Notably, these pathways are rich in catecholamines, which have been implicated in ADHD by the mechanism of action of stimulants--the class of drugs that effectively treats many ADHD children. Yet human studies of the catecholamine hypothesis of ADHD have produced conflicting results, perhaps due to the insensitivity of peripheral measures.

Adult↗
PubMed1998

Neuropsychological function in adults with attention-deficit hyperactivity disorder.

BACKGROUND: Recent studies indicate that attention-deficit hyperactivity disorder (ADHD) persists into adulthood, but little is known about the neuropsychological features of adult ADHD. Our objective was to assess neuropsychological functioning in adults with ADHD with a battery of executive function tests. METHODS: Subjects were 64 unmedicated adults, 19-59 years of age, with DSM-III-R ADHD of childhood onset who met criteria for ADHD when referred in adulthood and 73 non-ADHD controls of similar age and gender. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Compared with controls, adults with ADHD were significantly impaired on measures of vigilance, semantic encoding for verbal memory, and written arithmetic, irrespective of age, gender, psychiatric comorbidity, or presence of learning disability. Despite comparable educational level and IQ, ADHD adults had a trend to lower occupational attainment and had significantly more academic problems in school. CONCLUSIONS: These executive, attention, and achievement dysfunctions demonstrated in adults with ADHD provide additional support for the validity of the syndrome in adults.

Adult↗
PubMed1998

Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence?

BACKGROUND: The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) in adults has been the focus of much clinical and scientific inquiry. In this study we examine the effects of ADHD on the transitions from substance abuse to dependence and between different classes of agents of abuse. METHODS: An ADHD sample of 239 consecutively referred adults of both genders with a clinical diagnosis of childhood-onset and persistent DSM-III-R ADHD confirmed by structured interview were compared with 268 non-ADHD healthy adults. RESULTS: ADHD was associated with a twofold increased risk for PSUD. ADHD subjects were significantly more likely than comparisons to make the transition from an alcohol use disorder to a drug use disorder (hazard ratio = 3.8) and were significantly more likely to continue to abuse substances following a period of dependence (hazard ratio = 4.9). CONCLUSIONS: ADHD is associated with a sequence of PSUD in which early alcohol use disorder increases the risk for subsequent drug use disorder, and early substance dependence increases the risk for subsequent substance abuse. If confirmed such developmental pathways might lead to preventive and early intervention strategies aimed at reducing the risk for PSUD in ADHD subjects.

Adult↗
PubMed1998

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness.

Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families.

Adolescent↗
PubMed1998

Familial risk analysis of the association between attention-deficit/hyperactivity disorder and psychoactive substance use disorders.

OBJECTIVE: To test hypotheses about patterns of familial association between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorders (PSUDs) by using the family study method. DESIGN: The first-degree relatives of clinically referred children and adolescents with ADHD (131 probands, 413 relatives) and healthy control probands (106 probands, 323 relatives) were assessed by blind raters. RESULTS: After stratifying the probands with ADHD and the control probands into those with PSUD (group 1 and group 3, respectively) and those without PSUD (group 2 and group 4, respectively), familial risk analyses revealed the following: (1) the risk for ADHD was not significantly different between relatives of group 2 and group 1 probands (19.6% vs 18.0%; P= .88), but these 2 risks were significantly greater than the risk to relatives of group 3 probands (1.0%; P= .01 and P= .02, respectively) and group 4 probands (7.0%; P=.001 and P=.01, respectively); (2) there were no significant differences in the risk for PSUD between relatives of group 1 (47.5%) and group 3 probands (39.7%; P = .40), but these risks were greater than the risk to relatives of group 2 (30.0%; P = .32) and group 4 probands (20.9%; P<.001); and (3) there was no evidence for nonrandom mating. CONCLUSIONS: These findings are consistent with the hypothesis that ADHD and PSUD are transmitted independently in families. Because the probands were young adolescents, many have not lived through the age at risk for PSUD. Thus, the hypothesis stating that ADHD and PSUD represent variable expressions of a common underlying risk factor cannot be ruled out.

Adolescent↗
PubMed1998

Normalized functioning in youths with persistent attention-deficit/hyperactivity disorder.

OBJECTIVE: The goal of this study was to examine normalization of functioning among youths with persistent attention-deficit hyperactivity/disorder (ADHD) symptoms. RESEARCH DESIGN: Subjects were 85 referred boys with persistent ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) who were followed up prospectively into mid adolescence and 68 boys without ADHD. These subjects were assessed at baseline and follow-up visits by using measures from 3 domains of functioning: school, social, and emotional. For each of these domains, we defined boys with ADHD as having normalized functioning if they attained scores above the 5th percentile of scores in the non-ADHD group. RESULTS: Twenty percent of boys with ADHD were functioning poorly in all 3 domains, 20% were functioning well in all 3 domains, and 60% had intermediate outcomes. Increased exposure to maternal psychopathology, larger family size, DSM-III-R psychiatric comorbidity, and symptoms of impulsivity were negatively associated with normalization of functioning among children with persistent ADHD. CONCLUSION: Our results show that children with ADHD have a variable emotional, educational, and social adjustment despite syndromatic persistence. This suggests that normalization of functioning and syndromatic persistence of ADHD may be partially independent.

Adolescent↗
PubMed1998

Depression in attention deficit hyperactivity disorder (ADHD) children: "true" depression or demoralization?

BACKGROUND: The purpose of this study was to further evaluate the nature of the association between major depression (MD) and attention deficit hyperactivity disorder (ADHD) by examining predictors of persistence of MD attending to issues of familiality, adversity and comorbidity. METHODS: Four years of follow-up of 76 depressed ADHD children were analyzed using multivariate regression to determine predictors of persistent MD. RESULTS: Bipolar disorder and higher indices of interpersonal problems predicted MD persistence. In contrast, school difficulty and ADHD-associated measures of severity were not associated with persistent MD. Remission from ADHD was also not statistically significantly associated with remission from MD. CONCLUSIONS: ADHD and MD had independent and distinct courses, indicating that ADHD-associated MD reflects a depressive disorder and not merely demoralization. LIMITATIONS: This study may have reduced power due to stratification of our group of ADHD boys with persistent and remitting MD.

Adolescent↗
PubMed1998

Clinical features of children with both ADHD and mania: does ascertainment source make a difference?

OBJECTIVE: We evaluated the structural diagnostic results of children ascertained through an ADHD diagnosis with comorbid mania to determine if they have the same phenotype as children ascertained through a mania diagnosis with comorbid ADHD. METHOD: We compared a sample of children participating in a family genetic study of ADHD to a sample of children ascertained through a study of childhood mania. RESULTS: Similar correlates of ADHD and mania were observed in children satisfying criteria for both disorders irrespective of ascertainment source. CONCLUSIONS: Findings suggest that children with mania and ADHD have two disorders, their features not varying with the primary diagnostic focus. LIMITATIONS: The results may have been limited by small sample size. CLINICAL RELEVANCE: Because the coexistence of ADHD and mania seriously complicates the course and treatment of children, understanding the compatibility of these disorders has important clinical implications in the management of this population.

Adolescent↗
PubMed1998

Psychiatric, neuropsychological, and psychosocial features of DSM-IV subtypes of attention-deficit/hyperactivity disorder: results from a clinically referred sample.

OBJECTIVE: To assess the validity of the DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD). METHOD: Using structured diagnostic interviews and psychometric measures of cognitive and social functioning, the authors assessed 413 children and adolescents consecutively referred to a pediatric psychopharmacology clinic since 1991. RESULTS: Marked psychiatric differences were found among DSM-IV subtypes of ADHD, but few differences were found in cognitive or psychosocial functioning. The greatest psychiatric differences were found between the combined-type subjects (who tended to show more impairment in multiple domains) and the other two subgroups. The inattentive patients, however, were more likely to have required extra help in school. The hyperactive-impulsive patients were not different from controls on rates of depression, Child Behavior Checklist measures of social functioning, or psychometric measures of intellectual functioning and academic achievement. CONCLUSIONS: The results suggest that, regarding clinical features, combined-type patients have a more severe disorder than the other DSM-IV subtypes.

Adolescent↗
PubMed1998

Diagnostic continuity between child and adolescent ADHD: findings from a longitudinal clinical sample.

OBJECTIVE: To determine whether there are differences in the clinical expression and correlates of attention-deficit hyperactivity disorder (ADHD) between children and adolescents. METHOD: Subjects were 6- to 17-year old Caucasian, non-Hispanic boys with and without ADHD. DSM-III-R structured diagnostic interviews, psychometric measures, and blind raters assessed psychiatric diagnoses, intellectual performance, social disability, school failure, and family functioning. RESULTS: Children and adolescents with ADHD had an almost identical pattern of correlates in multiple domains of assessment including psychosocial adversity and comorbidity with conduct, mood, and anxiety disorders. Although the rate of substance abuse differed in comparison between child and adolescent subjects, this was independent of ADHD status. CONCLUSIONS: These findings document the diagnostic continuity of ADHD between childhood and adolescence and support the inclusion of adolescent samples in ADHD research protocols.

Adolescent↗
PubMed1998

Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature.

OBJECTIVE: To examine the clinical correlates of obsessive-compulsive disorder (OCD) in children and adolescents. METHOD: A systematic review of the extant literature on juvenile OCD was conducted examining age at onset, gender distribution, symptom phenomenology, psychiatric comorbidity, neurological and perinatal history, family psychiatric history, cognitive and neuropsychological profiles, and treatment and outcome in juvenile OCD subjects. RESULTS: Juvenile OCD was associated with a unique peak of age at onset indicating a bimodal incidence of the disorder, male preponderance, a distinct pattern of comorbidity with attention-deficit/hyperactivity disorder and other developmental disorders as well as frequent associated neuropsychological deficits, an increased familial loading for OCD, and frequent absence of insight. CONCLUSION: These findings show that juvenile OCD is associated with a unique set of correlates that appear to differ from findings reported in studies of adult OCD subjects. Although in need of confirmation, these findings suggest that juvenile OCD may be a developmental subtype of the disorder. Since juvenile OCD is likely to continue into adulthood, these findings stress the importance of considering age at onset in clinical and research studies of adults with OCD.

Adolescent↗