Genetic markers, temperament, and psychopathology.
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Adult↗
Biomedical subjects
J Biederman
Publications and source records attributed to J Biederman.
An exploratory study of ADHD among second-degree relatives of ADHD children.
Family-genetic studies consistently show that attention deficit hyperactivity disorder (ADHD) aggregates in nuclear families. Little is known about the aggregation of ADHD in second-degree relatives. We examined the prevalence of ADHD in second-degree relatives of 140 ADHD probands and 120 normal controls. Information pertinent to the diagnosis of ADHD in second-degree relatives was collected from the probands' parents. The second-degree relatives of ADHD probands were at increased risk for ADHD compared with the second-degree relatives of normal control probands. These risks were greatest when the second-degree relative was biologically related to an ADHD parent of an ADHD proband. Consistent with the greater prevalence of ADHD among boys compared with girls, grandfathers were at greater risk than grandmothers and uncles were at greater risk than aunts. Our results support the usefulness of ascertaining information from second-degree relatives in studies evaluating the genetic epidemiology of ADHD. If confirmed, such studies may help clarify the mechanism of familial transmission of ADHD.
Attention Deficit Disorder with Hyperactivity↗
Gender differences in a sample of adults with attention deficit hyperactivity disorder.
Although originally conceptualized as a childhood disorder, attention deficit hyperactivity disorder (ADHD) may also be an adult disorder. However, despite increasing media attention to adult ADHD, its validity has only recently been studied in a systematic fashion. The overrepresentation of females in adult samples in comparison to pediatric samples of ADHD raises additional questions about the validity of this disorder in adults. The goal of this article is to explore whether ADHD is a valid clinical entity in female subjects and whether it is expressed differently in male and female adults. To this end, we examined the clinical, cognitive, and functional characteristics of 128 referred adult ADHD cases of both sexes. Each subject had a clinical diagnosis of childhood-onset ADHD confirmed by structured interview. The male and female ADHD adults were similar to one another but more disturbed and impaired than non-ADHD adult control subjects. Compared with normal control females, ADHD women had higher rates of major depression, anxiety disorders, and conduct disorder; and more evidence of school failure and cognitive impairment. The consistency of these findings in both genders further supports the validity of the diagnosis of ADHD in adults. Our results stress the viability and importance of identification of female subjects with ADHD. The underidentification and undertreatment of females with ADHD may have substantial mental health and educational implications, suggesting that research is needed to develop a better understanding of clinical indicators of ADHD in females.
Adult↗
DSM-IV field trials for the disruptive behavior disorders: symptom utility estimates.
OBJECTIVE: We tested the predictive utility of symptoms for proposed DSM-IV definitions of the disruptive behavior disorders using indices corrected for symptom and diagnosis base rates. METHOD: The field trials sample consisted of 440 clinic-referred youths who were consecutive referrals to a heterogeneous group of mental health clinics. Multiple informants were interviewed to determine the presence of symptoms and diagnoses. RESULTS: Some symptoms which were either not in DSM-III or DSM-III-R, or were modifications of DSM-III-R symptoms, had greater diagnostic efficiency than did several existing symptoms. Symptom utility estimates were generally similar for different ages and genders, although some interesting age and sex trends emerged for a few symptoms. CONCLUSIONS: The results supported the inclusion of more restricted definitions of "lying" and "truancy" to increase their association with a conduct disorder diagnosis and they supported the elimination of "swearing" in the oppositional defiant disorder criteria. In addition to their relevance for developing optimal criteria for DSM-IV, these results can aid DSM-IV users by providing a useful guide to the relative efficiency of individual symptoms based on data from a large heterogeneous clinic population.
Adolescent↗
Tricyclic antidepressant treatment of children with ADHD and tic disorders.
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Adolescent↗
DSM-IV field trials for attention deficit hyperactivity disorder in children and adolescents.
OBJECTIVE: Optimal diagnostic thresholds were determined for DSM-IV attention deficit hyperactivity disorder, and the psychometric properties were compared to alternative definitions. METHOD: Structured diagnostic interviews of multiple informants for 380 clinic-referred youths aged 4-17 years were conducted. In addition, standardized clinicians' validation diagnoses of attention deficit disorder were obtained to assess agreement with clinical judgment. Measures of impairment were obtained to assess the accuracy of identifying youth with an impairing condition. RESULTS: Three subtypes of attention deficit hyperactivity disorder (predominantly inattentive, predominantly hyperactive-impulsive, and combined types) were distinguished on the basis of the degree of deviance on separate dimensions of inattention and hyperactivity-impulsivity. These three subtypes were found to differ in terms of types of impairment, age, and sex ratio, but not ethnicity. In terms of case identification of attention deficit hyperactivity disorder, DSM-IV was found to be very similar to DSM-III-R, except that DSM-IV identified more impaired girls and preschool children. CONCLUSIONS: These results support the decision to subdivide the heterogeneous category of DSM-III-R attention deficit hyperactivity disorder into three subtypes. The resulting DSM-IV definition appears to be somewhat less biased toward the symptom pattern typical of elementary school boys.
Adolescent↗
Comorbidity of attention-deficit hyperactivity and psychoactive substance use disorders.
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Adolescent↗
The etiology of social phobia.
Human beings are by nature social animals, but for some, social scrutiny is a source of extreme anguish. Those with social phobia, for example, suffer excessive and often disabling concern about potential and real social-evaluative threat. As new and effective therapies for this condition are pursued, there is a simultaneous movement to extend the understanding of this disorder's etiology. In psychiatry, as in the rest of medicine, this development of new treatments often occurs in parallel with increasing sophistication about causes of illness. Advances in one area typically inform and predictably lead to advances in the other. Social phobia is recognized as a relatively common and significantly impairing anxiety disorder. As with other psychiatric disorders, emerging models of the etiology of social phobia are derived from converging evidence of interacting biological and environmental contributions. Current theories regarding the evolution of social phobia will be addressed, including biological preparedness to fear scrutiny by others, genetically transmitted predisposition to fear acquisition, nongenetic familial and environmental factors, as well as other possible causes and antecedents. Additionally, we describe recent work on behavioral inhibition in infancy as an identifiable early marker of proneness to the development of anxiety disorders, including social phobia.
Adolescent↗
Efficiency of diagnostic criteria for attention deficit disorder: toward an empirical approach to designing and validating diagnostic algorithms.
Using structured psychiatric interviews, 73 attention deficit disorder (ADD) patients, 26 psychiatric control patients, 26 normal controls, and all available first degree relatives of these index children were examined. ADD subgroups with and without comorbid psychiatric disorders did not differ on rates of specific ADD symptoms. The construct of ADD is internally consistent as measured by Cronbach's alpha. The diagnostic efficiency of individual items is presented. A receiver operating characteristic-based procedure is used to create an ADD diagnostic algorithm that is more efficient in discriminating ADD children from controls than the DSM-III-based clinical diagnosis. Cross-validation with family study data shows this procedure to be superior to the procedure used for the DSM-III-R diagnosis. The results show that proponents of conditional probability and receiver operating characteristic analyses are correct in asserting that the examination of symptom combinations may result in better diagnostic algorithms.
Algorithms↗
A double-blind placebo controlled study of desipramine in the treatment of ADD: III. Lack of impact of comorbidity and family history factors on clinical response.
A 6-week randomized, double-blind, placebo controlled trial of desipramine (DMI) in daily doses averaging 4 to 5 mg/kg for the treatment of children and adolescents with attention deficit disorder with hyperactivity (ADDH) was further analyzed. Investigators examined whether comorbidity of ADDH with conduct disorder, major depression, an anxiety disorder, or a family history of ADDH predicted response to DMI treatment. There was a highly significant effect of treatment with DMI in outcome assessments, but responses to DMI were indistinguishable in ADDH patients with and without a comorbid disorder or familial ADDH. Cases of "pure" ADDH (lacking comorbidity with depression, anxiety, or conduct disorder and having a positive family history of ADDH) showed a trend toward lesser placebo responses and a corresponding greater DMI-placebo difference. These findings suggest that (1) DMI is effective in simple, noncomorbid cases, (2) DMI is not selective for comorbid cases, but (3) a response to DMI can be obtained even in complex cases of ADDH with associated comorbidity.
Adolescent↗
Nortriptyline treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome.
Although as many as 50% of patients with Tourette's syndrome (TS) also meet diagnostic criteria for Attention-deficit Hyperactivity Disorder (ADHD), until recently little attention has been paid to ADHD symptoms in the assessment of therapeutic outcome of TS or patients with chronic motor tics (CMT). Because antipsychotics are of limited value in controlling the symptoms of ADHD and stimulants can exacerbate tics, alternative treatments for patients with chronic tic disorder (CTD) (TS or CMT) plus ADHD (CTD+ADHD) patients are direly needed. We examined the efficacy of the tricyclic antidepressant nortriptyline in the treatment of pediatric patients with CTD+ADHD ascertained from systematic chart reviews of all subjects with this diagnosis treated with nortriptyline. Of the 12 identified patients, 67% had significant improvement in CTD symptomatology and 92% significantly improved ADHD symptoms without major adverse effects over an average follow-up period of 19 months. Although the conclusions from this retrospective report can be only seen as preliminary until replicated in a controlled investigation, the magnitude and persistence of the response is encouraging and suggest a therapeutic role for nortriptyline in the treatment of CTD+ADHD patients.
Adolescent↗
Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette's syndrome.
Concerns have been raised regarding the development of tics in some children with attention-deficit hyperactivity disorder (ADHD) receiving stimulants. Because in many patients with Tourette's syndrome (TS) the ADHD symptoms are the major source of disability, alternative nonstimulant treatments are needed. Initial reports on bupropion have suggested that it may be an effective alternative in children and adults with ADHD. The value of bupropion as an alternative treatment for patients with comorbid TS and ADHD is determined by the question of association with exacerbation of tics. The purpose of this study was to examine an apparent association with exacerbation of tics in patients with comorbid TS and ADHD. A careful retrospective analysis was conducted of clinic cases of patients who all had comorbid TS and ADHD treated with bupropion. We present four cases of children with ADHD and comorbid TS treated with bupropion in whom tics were exacerbated by this medicine. This series suggests that bupropion may not be an appropriate alternative to stimulants in the treatment of ADHD in TS.
Attention Deficit Disorder with Hyperactivity↗
A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents.
OBJECTIVE: We retrospectively evaluated a large pediatric population treated with nortriptyline (NT) in an outpatient psychopharmacology clinic to assess pharmacokinetic and electrocardiographic (EKG) effects. METHODS: A systematic search revealed 82 children and adolescents treated naturalistically with NT. All patients with available EKGs and serum NT levels were included in the series with the exception of those receiving concomitant antipsychotic agents. Forty-three percent of subjects were receiving medications in addition to NT. RESULTS: Patients received an average (+/- SE) NT dose of 2.0 +/- 0.1 mg/kg yielding mean serum NT levels of 105.5 +/- 7.4 ng/mL. There was a linear relationship of NT dose (mg/kg) to serum NT levels (r = 0.50, p < 0.0001). NT treatment resulted in small increases in heart rate, and PR, QRS, and QTc intervals (all ps < 0.01), of similar magnitude in children and adolescents. Individuals with the highest baseline EKG indices had the least amount of change in those indices with NT treatment. There were only a few statistically significant associations between NT dose or serum NT levels and EKG parameters. NT treatment was significantly associated with the onset of asymptomatic sinus tachycardia (heart rate > 100 beats per minute), and prolongation of the EKG QRS (> 100 msec) and QTc (> 440 msec) intervals. CONCLUSIONS: These findings suggest: (1) NT has a predictable dose to level relationship, (2) the effect of NT on the EKG in this age group is mild and similar to that reported with other tricyclic antidepressants, and (3) there are few age-specific differences in NT-induced EKG changes.
Adolescent↗
Diagnoses of attention-deficit hyperactivity disorder from parent reports predict diagnoses based on teacher reports.
OBJECTIVE: For DSM-III attention deficit disorder (ADD), it was previously reported that, when a parent report leads to a diagnosis of ADD, it is highly likely that the teacher report will also be positive. This report seeks to generalize that finding to DSM-III-R attention-deficit hyperactivity disorder (ADHD). METHOD: In a population of 34 children meeting clinical criteria for DSM-III-R ADHD, parents and teachers independently responded to questions about individual ADHD symptoms. RESULTS: Correlations between parents and teachers for individual symptoms were low to moderate; however, there was a 77% probability that the teacher report would result in a positive diagnosis given a positive parent diagnosis. This probability increased to 88% if "broad" teacher diagnoses of ADHD, defined by 35% of the 14 DSM-III-R symptoms, were included. CONCLUSIONS: In clinically-referred children, a clinical diagnosis of ADHD based on parent report is likely to be corroborated by a teacher report.
Attention Deficit Disorder with Hyperactivity↗
Nortriptyline in the treatment of ADHD: a chart review of 58 cases.
OBJECTIVE: The potential benefit of the tricyclic antidepressant medication, nortriptyline (NT), in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD) was evaluated. METHOD: A systematic search was conducted from a computerized data base of all clinic patients in an outpatient pediatric psychopharmacology unit treated with NT for ADHD. The records of the 58 subjects identified (37 children and 21 adolescents) were reviewed for overall response, dose, serum levels, and adverse effects. RESULTS: Ninety-seven percent of the identified subjects had failed to respond to an average of four previous medication trials, 84% had at least one comorbid diagnosis with ADHD, and 47% were receiving at least one concurrent medication. NT doses ranged from 0.4 to 4.5 mg/kg (X +/- SD = 2.0 +/- 1.0 mg/kg) and subjects received NT from 0.4 to 57.9 months (11.9 +/- 14.0 months). Overall, 76% of subjects were considered to have a moderate to marked improvement by an independent rater, which was corroborated by their clinicians. There was no association between response and age, rate of comorbidity, number of previous medication trials, or concurrent pharmacotherapy (all p NS). Although there were no overall differences in serum NT levels between responders and nonresponders, significantly more patients within the suggested therapeutic range in adults of 50 to 150 ng/ml were classified as "markedly improved" than those outside this range (68% versus 35%, p < 0.03). Mild adverse effects were reported in 20 subjects (34%). CONCLUSIONS: These findings suggest that NT may be an effective well-tolerated agent for ADHD children and adolescents. Additional controlled investigations utilizing NT for ADHD should be undertaken.
Adolescent↗
Comparison of clonidine response in the treatment of attention-deficit hyperactivity disorder with and without comorbid tic disorders.
OBJECTIVE: Clonidine has been suggested as an alternative pharmacotherapy for patients with attention-deficit hyperactivity disorder (ADHD) and comorbid tic disorders. To examine the efficacy of clonidine in this population of children, the use of clonidine in the treatment of children with ADHD with and without comorbid tic disorders was examined in a retrospective chart review of 54 children over a 4-year period. METHOD: Treatment was administered openly to these patients in a Pediatric Psychopharmacology Clinic, and response was assessed using clinical global improvement measures. RESULTS: Clonidine treatment resulted in improvement in both the ADHD (39/54; 72%) and tic symptoms (18/24; 75%) groups. The findings suggested that the children with ADHD with comorbid tic disorders (23/24; 96%) have a more frequent positive behavioral response to clonidine than children with ADHD without comorbid tic disorders (16/30; 53%). CONCLUSIONS: This report provides further support of a role for clonidine in the treatment of children with ADHD, particularly for those with comorbid tic disorders.
Adolescent↗
Desipramine treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome.
OBJECTIVE: As many as 50% of patients with Tourette's syndrome (TS) also meet diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Since antipsychotics are of limited value in controlling the symptoms of ADHD and stimulants can exacerbate tics, alternative treatments are directly needed. The purpose of this study was the examination of the efficacy of desipramine (DMI) in the treatment of pediatric patients with chronic tic disorder (CTD; TS or chronic motor tics) + attention-deficit hyperactivity disorder (ADHD). METHOD: All pediatric patients with the diagnosis of CTD that were treated with DMI were ascertained from retrospective systematic chart reviews of a psychopharmacology clinic and a neurology service specialized in movement disorders. RESULTS: Of the 33 identified patients, 30 had comorbid CTD + ADHD and three had CTD alone. In all, 82% had significant improvement in CTD symptomatology and 80% significantly improved ADHD symptoms without major adverse effects over an average follow-up period of 16 months. CONCLUSIONS: Although the conclusions from this retrospective report can be seen as preliminary only until replicated in a controlled investigation, the magnitude and persistence of the response is encouraging and suggest a therapeutic role for DMI in the treatment of CTD + ADHD patients.
Adolescent↗
Electrocardiographic effects of desipramine and 2-hydroxydesipramine in children, adolescents, and adults treated with desipramine.
OBJECTIVE: To assess the developmental effects of desipramine (DMI) treatment on the electrocardiogram (ECG), we investigated serum concentrations of DMI ([DMI]), and its major active metabolite 2-hydroxydesipramine ([OHDMI]) and ECG parameters. METHODS: ECGs and [DMI] and [OHDMI] were analyzed from 50 children, 39 adolescents, and 30 adult psychiatric patients receiving DMI. RESULTS: There were modest overall correlations between [DMI], [OHDMI], or [OHDMI+DMI], and the PR and QRS intervals when data from all 119 subjects were pooled. Within the pediatric age groups there were no significant associations between serum drug levels and heart rate or conduction intervals; and in all subjects with ECG abnormalities, there were some findings of higher [DMI], [OHDMI], and [OHDMI+DMI]. CONCLUSIONS: These findings indicate that only modest associations of [DMI] and [OHDMI] with ECG conduction intervals were found, and are not likely to be clinically significant in any of the age groups studied. Compared with adults, children and adolescents do not appear to be at increased risks for ECG changes related to DMI treatment or to circulating concentrations of [DMI] or [OHDMI].
Adolescent↗