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Biomedical subjects

Joseph Biederman

Publications and source records attributed to Joseph Biederman.

At least 55 records · Page 3Linked to original sources
PubMed2006

Laboratory-observed behavioral disinhibition in the young offspring of parents with bipolar disorder: a high-risk pilot study.

OBJECTIVE: This study tested whether behavioral disinhibition is more prevalent among offspring of parents with bipolar disorder than among offspring of parents without bipolar disorder. METHOD: The authors conducted a secondary analysis of data from a preexisting high-risk study of offspring at risk for panic disorder and depression (N=278) that had included some children with parents who had bipolar disorder (N=34). Children (ages 2-6) had been classified as behaviorally inhibited, disinhibited, or neither in laboratory assessments. RESULTS: Offspring of bipolar parents had significantly higher rates of behavioral disinhibition than offspring of parents without bipolar disorder. Behavioral inhibition did not differ between groups. Differences were not accounted for by parental panic disorder or major depression or by parental history of attention deficit hyperactivity disorder, conduct disorder, antisocial personality, or substance use disorders. CONCLUSIONS: Results suggest a familial link between bipolar disorder in parents and behavioral disinhibition in their offspring. Behavioral disinhibition may be a familially transmitted predisposing factor for dysregulatory distress later in life.

Age Factors↗
PubMed2006

Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: a proton magnetic resonance spectroscopy study.

OBJECTIVE: The authors' goal was to investigate phosphatidylinositol and glutamatergic metabolism in the anterior cingulate cortex of children and adolescents with attention deficit hyperactivity disorder (ADHD) alone, children with ADHD plus bipolar disorder, and children with no axis I diagnosis. METHOD: Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were healthy comparison subjects. RESULTS: Children with ADHD had a significantly higher ratio of glutamate plus glutamine to myo-inositol-containing compounds than children with ADHD plus bipolar disorder and healthy children. CONCLUSIONS: myo-Inositol-containing compounds may provide information on the action of antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and glutamine are measures of glutamatergic neurotransmission and thus may also reflect changes in serotonin and dopamine pathways.

Adolescent↗
PubMed2006

PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate.

OBJECTIVE: The abuse potential of methylphenidate has been related to the drug's capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would also produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate. METHOD: Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (C(max)) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses to detection/likeability questionnaire items were obtained hourly for 10 hours after administration of methylphenidate on two separate occasions for each subject. Dopamine transporter receptor occupancies were measured at hours 1, 3, 5, and 7 by using a carbon-11-labeled imaging agent (Altropane) and positron emission tomography. RESULTS: Despite similar C(max) values for both formulations, osmotic-release methylphenidate was associated with a longer time to maximum concentration, longer time to maximum CNS dopamine transporter occupancy, and no detection/likeability, compared with immediate-release methylphenidate. CONCLUSIONS: The findings suggest that the abuse potential of oral methylphenidate is strongly influenced by the rate of delivery and not solely by the magnitude of plasma concentration or brain transporter occupancy. These results advance understanding of the underlying central effects of methylphenidate in humans and identify a potentially less abusable methylphenidate formulation.

Administration, Oral↗
PubMed2006

Adults with ADHD and sleep complaints: a pilot study identifying sleep-disordered breathing using polysomnography and sleep quality assessment.

OBJECTIVE: ADHD and sleep-disordered breathing are both prevalent in adulthood. Because both conditions may be responsible for similar symptoms of cognitive impairment, the authors investigate whether their presentation may overlap in adults diagnosed with ADHD. METHOD: Data are collected from six adults with sleep complaints who were diagnosed with ADHD using rigorous clinical criteria. All participants undergo overnight polysomnography and complete questionnaires about sleep quality, circadian sleep pattern, and daytime fatigue. RESULTS: On standardized measures, all participants report poor sleep quality, two report daytime fatigue, and none report distinct deviation from normal sleep and wake cycle pattern. Polysomnography reveals evidence of sleep-disordered breathing and sleep fragmentation in all participants. CONCLUSION: Objective evidence of breathing-related sleep disorders can be found in some adults with carefully diagnosed ADHD who report sleep complaints. This report highlights the importance of identifying treatable sleep disorder comorbidity in adults with ADHD.

Adult↗
PubMed2006

Symptoms versus impairment: the case for respecting DSM-IV's Criterion D.

Diagnosing ADHD based primarily on symptom reports assumes that the number/frequency of symptoms is tied closely to the impairment imposed on an individual's functioning. That presumed linkage encourages diagnosis more by Diagnostic and Statistical Manual of Mental Disorders (4th ed.) style symptom lists than well-defined, psychometrically sound assessments of impairment. The current study correlated measures reflecting each construct in four separate, large-scale ADHD research samples. Average correlation between symptoms and impairment accounted for less than 10% of variance. Symptoms never predicted more than 25% of the variance in impairment. When an ADHD group was formed according to a measure of current symptoms, the sample size shrunk by 77% when a criterion-based measure of impairment was added. The partial unlinking of symptoms and impairment has implications for decisions about the diagnostic process, research criteria for participant inclusion, prevalence estimates, gender ratios, evaluation of treatment effects, service delivery, and many other issues.

Adolescent↗
PubMed2006

Donepezil in the treatment of ADHD-like symptoms in youths with pervasive developmental disorder: a case series.

BACKGROUND: Recent studies reported ADHD-like symptoms and cognitive deficits in pervasive developmental disorder (PDD). Because work in dementia documents improvement in executive function deficits with the acetylcholinesterase inhibitor donepezil, the authors reason that similar benefits could be obtained in PDD. METHOD: The authors describe eight cases of PDD youth ages 10 to 17 treated with donepezil targeting ADHD-like symptoms associated with PDD. RESULTS: Most participants improve ADHD-like symptomatology. In addition, improvement in communication and socialization is noted. CONCLUSION: Donepezil may have a role in treating ADHD-like symptoms in children with PDD.

Adolescent↗
PubMed2006

Stimulants and sudden death: what is a physician to do?

OBJECTIVE: Recently, a US Food and Drug Administration advisory committee raised concerns about cardiovascular risks and sudden death in children and adolescents with attention-deficit/hyperactivity disorder who are receiving stimulants. METHODS: We comment on the risk of sudden death in children/adolescents taking stimulants compared with population rates, biological plausibility, and known cardiovascular effects of stimulants to determine specific risk. RESULTS: There does not seem to be higher risk of sudden death in stimulant-treated individuals compared with the general population. Although there is evidence of biological plausibility, the known effects of the stimulants on cardiovascular electrophysiology and vital signs seem to be benign. CONCLUSIONS: There does not seem to be compelling findings of a medication-specific risk necessitating changes in our stimulant treatment of children and adolescents with attention-deficit/hyperactivity disorder. The use of existing guidelines on the use of stimulants (and psychotropic agents) may identify children, adolescents, and adults who are vulnerable to sudden death.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Using self-reported data to assess the validity of driving simulation data.

In this article, we use self-reported driving behaviors from a written questionnaire to assess the measurement validity of data derived from a driving simulation. The issue of validity concerns the extent to which measures from the experimental context map onto constructs of interest. Following a description of the experimental methods and setting, an argument for the face validity of the data is advanced. Convergent validity was assessed by regressing behaviors observed in thedriving simulatoron self-reported measures of driving behaviors. Significant relationships were found across six measures: accidents, speeding, velocity, passing, weaving between traffic, and behavior at stop signs. Concurrent validity was evaluated with an analysis of simulator accident involvement and attention deficit hyperactivity disorder status. Discriminant validity was assessed using a multitrait-multimethod matrix of simulator and questionnaire data. We concluded that although the relationship between self-reported behaviors and observed responses in the simulator falls short of perfect correspondence, the data collected from the driving simulator are valid measures of the behaviors of interest.

Adolescent↗
PubMed2006

Modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation.

OBJECTIVE: The objective of this fixed-dose study was to determine the efficacy and safety of a new formulation of modafinil (modafinil film-coated tablets) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). In addition, the effect of abrupt discontinuation of modafinil was evaluated in a 2-week observation period. METHOD: Patients aged 6 to 17 years with DSM-IV-TR-defined ADHD were randomly assigned to 7 weeks of double-blind treatment with modafinil or placebo in a 2:1 ratio, followed by abrupt discontinuation of modafinil and a 2-week, double-blind observation period in which 46% of patients receiving modafinil were switched to placebo without tapering and half continued to receive modafinil. Study drug was administered once daily and titrated over the first 7 to 9 days to daily doses of 340 mg for patients < 30 kg or 425 mg for patients > or = 30 kg. Assessment instruments included the Attention-Deficit/ Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global Impressions-Improvement scale (CGI-I). The study was conducted from November 2003 to June 2004. RESULTS: A total of 190 patients were randomly assigned to receive modafinil (340 mg, N = 44; 425 mg, N = 82) or placebo (N = 64). 189 patients were evaluated for safety. Modafinil significantly improved symptoms of ADHD as shown by reductions in ADHD-RS-IV School Version total scores compared with placebo at all visits (p < or = .009), including the final visit of the double-blind phase (p < .0001). With modafinil, ADHD-RS-IV School Version mean total scores changed from 37.8 at baseline to 29.3 at week 1 and 20.7 at final visit; corresponding placebo values were 36.6, 32.8, and 28.4, respectively; effect size at final visit was 0.76 (95% CI = 0.63 to 0.88). Total scores on the ADHD-RS-IV Home Version were also significantly reduced at all visits (p < or = .022) and final visit (p = .001) in patients receiving modafinil compared with those receiving placebo. Significantly higher proportions of patients receiving modafinil were rated "much improved" or "very much improved" in overall clinical condition (CGI-I) at all visits compared with patients receiving placebo (p < .001). No withdrawal symptoms were observed when modafinil was abruptly discontinued at the beginning of the final 2-week observation period. Modafinil was generally well tolerated. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Sixty-three percent of patients who received modafinil completed the study; 13% discontinued because of lack of efficacy; 10%, because of adverse events; and 13%, for other reasons (e.g., consent withdrawn, lost to follow-up). CONCLUSION: Modafinil significantly improved symptoms of ADHD both at school and at home and was well tolerated by children and adolescents. Abrupt discontinuation of modafinil was not associated with symptoms of withdrawal or with rebound of symptoms of ADHD.

Adolescent↗
PubMed2006

Association between attention-deficit/hyperactivity disorder and bulimia nervosa: analysis of 4 case-control studies.

BACKGROUND: Impulsivity is a common feature of attention-deficit/hyperactivity disorder (ADHD), and evidence suggests that impulsivity traits may be an indicator of poor prognosis for individuals with bulimia nervosa. To identify whether there is an association between ADHD and bulimia nervosa, the authors systematically examined data from children and adults with and without ADHD. METHOD: We systematically identified rates of bulimia nervosa in individuals with and without ADHD (DSM-III-R criteria) in our 2 large pediatric and 2 large adult samples (N = 522 children, 742 adults). Subjects were assessed from the late 1980s to February 1999. RESULTS: In the 2 samples of adults with and without ADHD, significantly greater rates of bulimia nervosa were identified in women with versus without ADHD (12% vs. 3%, p < .05 for 1 sample and 11% vs. 1%, p < .05 for the other sample). No significant differences in rates of bulimia nervosa were identified in men or children with ADHD when compared to sex-matched control subjects. CONCLUSION: Although preliminary and requiring further confirmation, these findings suggest that ADHD may be associated with bulimia nervosa in some women. If confirmed, this association between bulimia nervosa and ADHD could have important clinical and therapeutic implications.

Adolescent↗
PubMed2006

Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity.

OBJECTIVE: The objective of this study was to determine if measures of broad clinical psychopathology or neuropsychological performance could aid in the prediction of therapeutic response to the highly selective norepinephrine transporter inhibitor, atomoxetine, among adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: We analyzed data from 2 double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomly assigned to 10 weeks of treatment with atomoxetine or placebo and were assessed with Conners' Adult ADHD Rating Scales (CAARS), the General Well-Being Schedule (GWB), the Sheehan Disability Scale, the Stroop Color-Word Test (SCWT), and the Structured Clinical Interview for DSM-IV (SCID) before and after treatment. RESULTS: Therapeutic improvement on atomoxetine as evidenced by reduced CAARS scores was reliably predicted by the presence of a lifetime comorbid diagnosis of depression or post-traumatic stress disorder at baseline, while improvement on subscales of the GWB and Sheehan Disability Scale were predicted by these and other SCID endorsements, such as alcohol and substance use, as well as demographics such as age and gender. In light of the exploratory nature of this work and the many comparisons that were examined in the corresponding regression models, these findings should be regarded as tentative pending replication and extension in another dataset. CONCLUSION: From these findings, we conclude that the variable responsiveness of individuals to atomoxetine cannot be largely accounted for by differences in broad-spectrum psychopathology or neuropsychological indicators of attentional capacity.

Adrenergic Uptake Inhibitors↗
PubMed2006

Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community.

OBJECTIVE: The objective of this study was to evaluate functional impairments in a nonreferred sample of adults identifying themselves as having been diagnosed with attention-deficit/hyperactivity disorder (ADHD) by a clinician in their community. METHOD: We completed a survey in April and May 2003 of a community sample of 500 adults who reported having received a diagnosis of ADHD in the community and 501 gender- and age-matched comparisons from a national sample representative of the U.S. population. RESULTS: Adults with self-reports of diagnosed ADHD in the community were significantly less likely to have graduated high school (83% vs. 93% of controls; p < or = .001) or obtain a college degree (19% vs. 26%; p < .01), were less likely to be currently employed (52% vs. 72%; p < or = .001), and had significantly more mean job changes over 10 years (5.4 vs. 3.4 jobs; p < or = .001). They also were significantly more likely to have been arrested (37% vs. 18% of controls; p < or = .001) or divorced (28% vs. 15%; p < or = .001) and were significantly less satisfied (p < or = .001) with their family, social, and professional lives. CONCLUSION: Adults who reported having received a diagnosis of ADHD in the community had significant impairment in multiple domains of functioning compared with age- and gender-matched controls without this diagnosis, highly consistent with findings derived from carefully diagnosed referred samples.

Adolescent↗
PubMed2006

Characterizing impaired driving in adults with attention-deficit/hyperactivity disorder: A controlled study.

OBJECTIVE: We sought to confirm previously documented findings that individuals with attention-deficit/hyperactivity disorder (ADHD) demonstrate impaired driving behavior when compared with controls. METHOD: Subjects were adults with (N = 26) and without (N = 23) DSM-IV ADHD ascertained through clinical referrals to an adult ADHD program and through advertisements in the local media. Driving behavior was assessed using the Manchester Driving Behavior Questionnaire (DBQ) and 10 questions from a driving history questionnaire. Neuropsychological testing and structured interviews were also administered to all subjects. RESULTS: Substantially more ADHD subjects had been in an accident on the highway (35% vs. 9%, p = .03) or had been rear-ended (50% vs. 17%, p = .02) compared with controls. Analysis of the DBQ findings showed that ADHD subjects had significantly higher mean +/- SD scores than control subjects on the total DBQ (34.1 +/- 15.2 vs. 18.0 +/- 8.6, p < .001) and in all 3 subscales of the DBQ: errors (9.3 +/- 5.4 vs. 4.6 +/- 3.5, p < .001), lapses (12.4 +/- 6.2 vs. 6.1 +/- 3.5, p < .001), and violations (12.4 +/- 5.2 vs. 7.4 +/- 4.1, p < .001). Using the score that separated ADHD from control drivers on the DBQ as a cutoff, ADHD drivers at high risk for poor driving outcomes had more severe rates of comorbidity and exhibited more impaired scores on neuropsychological testing. CONCLUSIONS: Our results confirm and extend previous work documenting impaired driving behavior in subjects with ADHD. Results also suggest that ADHD individuals at high risk for poor driving behavior might be distinguishable from other ADHD individuals on DBQ scores, neuropsychological deficits, and patterns of comorbidities.

Accidents, Traffic↗
PubMed2006

An open-label study of the tolerability of mixed amphetamine salts in adults with attention-deficit/hyperactivity disorder and treated primary essential hypertension.

OBJECTIVE: To evaluate the short-term tolerability of an extended-release preparation of the stimulant medication mixed amphetamine salts (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) whose hypertension has been successfully treated with antihypertensive medications. METHOD: An 8-week, 2-phase, open-label study design was implemented. All adults had ADHD (DSM-IV diagnosis) and essential hypertension and were required to be normotensive (blood pressure < 135/85 mm Hg, treated) for at least 4 weeks at entry into the study. MAS XR was given for a 6-week period, titrated once each week to a target maximum dose of 60 mg/day given once daily in the morning (phase 1), and then discontinued for 2 weeks at the end of the study (phase 2). At baseline, subjects underwent a comprehensive clinical assessment, medical history, vital signs assessment, and electrocardiogram (ECG). Rating scales were used throughout the study to assess response to treatment, and blood pressure was measured manually at each study visit. The primary outcome was the effect of MAS XR on blood pressure and the development of hypertension. RESULTS: Thirteen subjects receiving antihypertensive therapy were entered and placed on MAS XR treatment and completed the trial. There were no serious adverse events. No sustained elevated blood pressure (> 140/90 mm Hg at 2 consecutive visits) was observed in the subjects treated with MAS XR. Similar rates of single episodes of hypertension were observed in phases 1 and 2. Similarly, there was no group mean increase in systolic or diastolic blood pressure or pulse during treatment with MAS XR. No clinically significant changes in the ECG were observed. During the 6-week medication phase, significant improvement was found on rating scales assessing ADHD symptoms and severity that reversed with discontinuation of MAS XR. CONCLUSION: The results of this open study suggest that adults with ADHD and controlled hypertension can be safely treated with MAS XR.

Adult↗
PubMed2006

A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebo-controlled study.

OBJECTIVE: This randomized, double-blind, placebo-controlled study assessed the efficacy and tolerability of several modafinil dosing regimens in children with attention-deficit/hyperactivity disorder (ADHD) to determine whether modafinil can be given once daily in pediatric ADHD. METHOD: Children and adolescents (age range, 6-13 years) (N = 248) with DSM-IV-defined ADHD were enrolled in a 4-week, double-blind, placebo-controlled study, conducted February-May 2002. The group was assigned to receive oral (100-mg tablets) modafinil 300 mg once daily (300 mg in the morning followed by placebo at midday), modafinil 300 mg as a divided dose (100/200 mg or 200/100 mg), or matching placebo. In children weighing > or = 30 kg, a higher dose of 400 mg (200/200 mg) was evaluated. Efficacy measures included the teacher-rated School Version and clinician-rated Home Version of the ADHD Rating Scale-IV and the parent-completed Conners' ADHD/DSM-IV Scales. RESULTS: 223 children completed the study. Those who received modafinil 300 mg once daily showed a significantly greater improvement (change from baseline) than those who received placebo in symptoms of ADHD across all rating scales and subscales (all p < .05). Divided 300-mg doses of modafinil provided some significant but inconsistent improvements in ADHD symptoms. In children weighing > or = 30 kg, modafinil 400 mg (200/200 mg) was significantly superior to placebo on clinician- and parent-completed scales (all p < .05). Insomnia was the only adverse event to occur with significantly greater frequency in a modafinil group (200/100) than in the placebo group (14% vs. 2%) (p = .03). CONCLUSION: Modafinil significantly improved ADHD symptoms in children. Once-daily dosing (300 mg) provided the most consistent improvement in symptoms. All dosing regimens of modafinil were well tolerated.

Adolescent↗
PubMed2006

Antecedents to panic disorder in nonreferred adults.

OBJECTIVE: Previous work has shown that childhood anxiety disorders are unique antecedents for panic disorder. The current study examined both childhood and adult comorbid disorders as potential antecedent disorders to panic disorder in a large sample of nonreferred adults. METHODS: Subjects were 1018 adults with (N = 58) and without (N = 960) panic disorder who were derived from a sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD); data were obtained from 1988 to 1996. Classification and regression trees (CART) analysis was used to examine anxiety and nonanxiety disorders antecedent to panic disorder. RESULTS: CART analysis showed that separation anxiety disorder, social phobia, and simple phobia were unique predictors of subsequent panic disorder. CONCLUSION: These results support and expand previously reported findings in referred samples documenting that comorbid anxiety disorders are unique antecedent risk factors for panic disorder.

Adult↗