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Biomedical subjects

Joseph Biederman

Publications and source records attributed to Joseph Biederman.

At least 19 recordsLinked to original sources
PubMed2006

Absence of association with DAT1 polymorphism and response to methylphenidate in a sample of adults with ADHD.

A polymorphism in the dopamine transporter gene (DAT1) has been previously associated with ADHD and methylphenidate has been hypothesized to block the dopamine transporter. The goal of this study was to examine whether a 40-bp variable number of tandem repeats (VNTR) of DAT1 moderate response and adverse effects associated with methylphenidate treatment of adults with ADHD. Subjects were 106 adults with ADHD enrolled in 6-week randomized placebo-controlled parallel design trials of methylphenidate (OROS and immediate release preparations). There was no evidence of an association between DAT1 VNTR and response to methylphenidate (F(2,100) = 0.04, P = 0.9). Similarly, there was no pattern of statistically significant association with DAT1 VNTR and cardiovascular or spontaneously reported adverse effects. We failed to identify an association with DAT1 and the response or tolerability of methylphenidate in adults with ADHD.

Adult↗
PubMed2006

Deriving phenotypes for molecular genetic studies of substance use disorders: a family study approach.

Although, family, twin, and adoption studies indicate that genes play a significant etiologic role in the development of substance use disorders (SUDs), the specific genes involved have been difficult to detect due, in part, to uncertainties about how best to define SUDs, the possibility of genetic heterogeneity and the variable phenotypic expression of SUD genotypes. The goal of the present work was to determine if phenotypes external to the diagnosis of SUD such as psychopathology and cognitive functioning would show evidence of utility as phenotypes for genetic studies of SUD. We did this by applying factor analysis to multiple measures collected from our family-study program and then determining if these factors were heritable and were co-familial with SUDs. We used data from families recruited into six contemporaneous studies of four psychiatric conditions in children and adults. We found evidence for two SUD related phenotypes. One was an index of Psychopathology and Psychosocial Impairment; the other was an index of school failure and cognitive dysfunction. Both factors showed evidence of heritability, longitudinal stability and familial association with Parental SUD but these findings were stronger for the index of school failure and cognitive dysfunction. Results provide some support for the idea that candidate SUD phenotypes such as psychopathology and cognitive functioning, which are external to the diagnostic criteria for SUDs, may be useful for genetic studies of SUD.

Adolescent↗
PubMed2006

Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data.

RATIONALE: Up to 60% of children with attention-deficit/hyperactivity disorder (ADHD) suffer from comorbid affective or behavioral impairments, the most common condition being oppositional defiant disorder (ODD), which occurs in 40-60% of children with ADHD. OBJECTIVES: This post hoc meta-analysis was performed to determine the effect of the presence of comorbid ODD symptoms on clinical outcomes among pediatric and adolescent subjects being treated for ADHD. METHODS: Acute-phase data were analyzed from three randomized, double-blind, placebo-controlled studies in outpatients aged 6-16 and meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects received placebo or atomoxetine (max 1.8 mg/kg/day, daily) for 6-8 weeks. Patients were diagnosed with comorbid ODD on structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-aged Children-Present and Lifetime Versions). RESULTS: Of the 512 subjects studied, 158 were diagnosed with comorbid ODD. Relative to placebo, atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects irrespective of the comorbidity with ODD. ADHD subjects also showed significant improvements from baseline on most of the psychosocial measures of the child health questionnaire irrespective of the comorbidity with ODD. Reduction in ODD symptoms was highly related to the magnitude of ADHD response. CONCLUSIONS: Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine.

Adolescent↗
PubMed2006

Psychopathology in the young offspring of parents with bipolar disorder: a controlled pilot study.

Studies have suggested that the offspring of parents with bipolar disorder are at risk for a spectrum of psychopathology, but few have focused on children in the youngest age ranges or examined the impact of comorbid parental disorders. We utilized a pre-existing sample of young (mean age: 6.8 years) offspring of parents with bipolar disorder (n=34), of parents with panic or major depression (n=179), and of parents with neither mood or anxiety disorder (n=95). Children were assessed blindly to parental diagnoses using the Schedule for Affective Disorders and Schizophrenia-Epidemiologic version (K-SADS-E). Offspring of bipolar parents had significantly higher rates of disruptive behavior and anxiety disorders than offspring from both of the comparison groups, accounted for by elevated rates of ADHD and overanxious disorder. These comparisons were significant even when lifetime histories of the corresponding categories of comorbid disorders in the parents (disruptive behavior disorders and anxiety disorders) were covaried. In addition, offspring of bipolar parents had increased rates of bipolar I disorder, compared with psychiatric controls. Results support the hypotheses of elevated behavior, anxiety, and mood disorders among offspring at risk for bipolar disorder, and suggest that this psychopathology is already evident in early childhood.

Adult↗
PubMed2006

Childhood antecedent disorders to bipolar disorder in adults: a controlled study.

OBJECTIVE: The aim of the study was to examine antecedent childhood psychiatric disorders in adult patients with bipolar disorder. METHOD: Using structured diagnostic interviews, childhood psychiatric diagnoses of 83 referred patients with diagnosed DSM-IV bipolar disorder were compared to those of 308 adults without mood disorders. RESULTS: Patients with bipolar disorder had significantly higher rates of childhood disruptive behavior disorders (ADHD, oppositional-defiant disorder, and conduct disorder), childhood anxiety disorders (separation anxiety and overanxious disorder), and enuresis, compared to patients without mood disorders. The presence of these childhood disorders was associated with an earlier age of onset of bipolar illness. LIMITATIONS: The retrospective nature of the study may have affected both the rates of disorders recalled, as well as the ages of onset of disorders. Different referral sources for bipolar and comparison participants may have also impacted findings. CONCLUSIONS: Bipolar disorder in adults is frequently preceded by childhood disruptive behavior and anxiety disorders. These childhood disorders may be important markers of risk for adult bipolar disorder.

Adult↗
PubMed2006

Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: a proton magnetic resonance spectroscopy study of the anterior cingulate cortex.

BACKGROUND: The purpose of this study was to investigate the anterior cingulate cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups of children with Bipolar Disorder (BPD): those exhibiting manic symptoms requiring treatment and those being stably treated with the atypical antipsychotic risperidone. Atypical antipsychotics have been shown to increase serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this study, we hypothesized that the children with BPD in need of treatment would have lower Glx/Cr compared with the children with BPD being stably treated with risperidone. METHODS: Proton MR spectra were acquired, at 1.5 T, from the ACC of eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10+/-3.48 years; five female) were manic and not medicated with any antipsychotic and eight (10.88+/-2.99 years; one female) were medicated with the atypical antipsychotic risperidone. RESULTS: Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania scores than the children not treated with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC Glx/Cr levels. LIMITATIONS: The cross-sectional design, small sample size, the use of Glx rather than glutamate or glutamine and the use of Cr ratios rather than absolute concentrations are limitations of this study. CONCLUSIONS: Children with mania have lower Glx/Cr levels than children with BPD being stably treated with the atypical antipsychotic risperidone. Mania may be associated with reduced glutamate/glutamine levels in the ACC: other imaging studies have shown mania associated with hypometabolism in the ACC. These reductions in glutamate/glutamine may be increased following successful treatment with glutamatergic agents.

Adolescent↗
PubMed2006

Examining the relationship between obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in children and adolescents: a familial risk analysis.

BACKGROUND: To use family study methodology to examine the relationship between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. METHODS: We assessed for ADHD and OCD in the 1533 first-degree relatives of three groups of index children: those with ADHD and OCD, those with ADHD but no OCD, and matched controls with neither disorder. RESULTS: The risk for ADHD was similarly elevated in families of ADHD youth with (18.9%) and without OCD (20.1%; p = .91), and both groups had significantly higher rates of ADHD compared with controls (4.6%; p < or = .001), which was consistent with previous research showing a strong familial risk for ADHD. The risk for OCD was significantly elevated only among relatives of youth with ADHD plus comorbid OCD (13.0%) compared with controls (.5%; p < or = .001) and was consistent with previous research showing a strong familial risk for OCD. Relatives affected with ADHD had a significantly elevated risk for OCD compared with relatives unaffected by ADHD (7.4% vs. 1.3%; p < .001), suggestive of co-segregation between these disorders. There was no evidence of nonrandom mating between ADHD- and OCD-affected spouses. CONCLUSIONS: These results extend previously reported findings regarding the heritability of both ADHD and OCD and provide new evidence of a familial relationship between ADHD and pediatric OCD that best fits the hypothesis of a unique familial subtype.

Adolescent↗
PubMed2006

Human cerebral cortex: a system for the integration of volume- and surface-based representations.

We describe an MRI-based system for topological analysis followed by measurements of topographic features for the human cerebral cortex that takes as its starting point volumetric segmentation data. This permits interoperation between volume-based and surface-based topographic analysis and extends the functionality of many existing segmentation schemes. We demonstrate the utility of these operations in individual as well as to group analysis. The methodology integrates analyses of cortical segmentation data generated by manual and semi-automated volumetric morphometry routines (such as the program cardviews) with the procedures of the FreeSurfer program to generate a cortical ribbon of the cerebrum and perform cortical topographic measurements (including thickness, surface area and curvature) in individual subjects as well as in subject populations. This system allows the computation of topographical cortical measurements for segmentation data generated from manual and semi-automated volumetric sources other than FreeSurfer. These measurements can be regionally specific and integrated with systems of cortical parcellation that subdivides the neocortex into gyral-based parcellation units (PUs). This system of topographical analysis of the cerebral cortex is consistent with current views of cortical development and neural systems organization of the human and non-human primate brain.

Adult↗
PubMed2006

Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with structural alterations in brain networks influencing cognitive and motor behaviors. Volumetric studies in children identify abnormalities in cortical, striatal, callosal, and cerebellar regions. In a prior volumetric study, we found that ADHD adults had significantly smaller overall cortical gray matter, prefrontal, and anterior cingulate volumes than matched controls. Thickness and surface area are additional indicators of integrity of cytoarchitecture in the cortex. To expand upon our earlier results and further refine the regions of structural abnormality, we carried out a structural magnetic resonance imaging study of cortical thickness in the same sample of adults with ADHD (n = 24) and controls (n = 18), hypothesizing that the cortical networks underlying attention and executive function (EF) would be most affected. Compared with healthy adults, adults with ADHD showed selective thinning of cerebral cortex in the networks that subserve attention and EF. In the present study, we found significant cortical thinning in ADHD in a distinct cortical network supporting attention especially in the right hemisphere involving the inferior parietal lobule, the dorsolateral prefrontal, and the anterior cingulate cortices. This is the first documentation that ADHD in adults is associated with thinner cortex in the cortical networks that modulate attention and EF.

Adolescent↗
PubMed2006

A randomized, double-blind study of continuation treatment for attention-deficit/hyperactivity disorder after 1 year.

BACKGROUND: The efficacy of atomoxetine in maintaining symptom response following 1 year of treatment was assessed in children and adolescents (n = 163) with DSM-IV defined attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects had previously responded to atomoxetine acutely and had completed 1 year of double-blind atomoxetine treatment. They were then randomly assigned in double-blind fashion to continued atomoxetine or placebo substitution for 6 months. RESULTS: Atomoxetine was superior to placebo in preventing relapse (Wilcoxon test, p = .008) and in maintaining symptom response (ADHD Rating Scale IV score, p < .001). Among subjects assigned to discontinuation, the magnitude of symptom return was generally to a level of severity less than that observed at study entry. CONCLUSIONS: Following 1 year of treatment with atomoxetine, continued treatment over the ensuing 6 months was associated with superior outcomes compared with placebo substitution. However, there was considerable variability between individuals in the magnitude of symptom return after drug discontinuation, suggesting that some subjects treated with atomoxetine for a year with good results may consolidate gains made during drug treatment and could benefit from a medication-free trial to assess the need for ongoing drug treatment.

Adolescent↗
PubMed2006

Neuropsychological studies of late onset and subthreshold diagnoses of adult attention-deficit/hyperactivity disorder.

BACKGROUND: Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve the DSM-IV threshold for diagnosis. Because neuropsychological deficits are associated with ADHD, we addressed the validity of the DSM-IV age at onset and symptom threshold criteria by using neuropsychological test scores as external validators. METHODS: We compared four groups of adults: 1) full ADHD subjects met all DSM-IV criteria for childhood-onset ADHD; 2) late-onset ADHD subjects met all criteria except the age at onset criterion; 3) subthreshold ADHD subjects did not meet full symptom criteria; and 4) non-ADHD subjects did not meet any of the above criteria. RESULTS: Late-onset and full ADHD subjects had similar patterns of neuropsychological dysfunction. By comparison, subthreshold ADHD subjects showed few neuropsychological differences with non-ADHD subjects. CONCLUSIONS: Our results showing similar neuropsychological underpinning in subjects with late-onset ADHD suggest that the DSM-IV age at onset criterion may be too stringent. Our data also suggest that ADHD subjects who failed to ever meet the DSM-IV threshold for diagnosis have a milder form of the disorder.

Adolescent↗
PubMed2006

Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging.

OBJECTIVES: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach. METHODS: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance had an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a priori hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups. RESULTS: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes. CONCLUSIONS: Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features.

Adult↗
PubMed2006

Comparison of parent and teacher reports of attention-deficit/hyperactivity disorder symptoms from two placebo-controlled studies of atomoxetine in children.

BACKGROUND: The validity of parent reports regarding children's attention-deficit/hyperactivity disorder (ADHD) symptoms has been questioned. This study assessed whether parent reports were as sensitive as teacher reports to document change in ADHD symptoms during clinical trials with atomoxetine. METHODS: Data were compared from two randomized, double-blind, placebo-controlled clinical trials of atomoxetine using different versions (parent or teacher) of the same rating scale (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV [parent or teacher] Version: Investigator Administered and Scored - ADHD RS). Exclusion criteria included history of bipolar disorder, psychosis, seizures, alcohol abuse, or positive drug screen. Patients (6-16 years old) were treated with atomoxetine (titrated to a maximum dose of 1.8 mg/kg/day) administered once daily for up to 7 weeks. Parent and teacher ratings were compared using an analysis of covariance (ANCOVA) model. RESULTS: The analysis (n = 318) showed that treatment effects (mean change, baseline to endpoint) were similar between parent and teacher ratings (total, p = .762; inattention, p = .519; hyperactive/impulsive, p = .955). Effect sizes also were similar based on total scores (parent ratings = .69; teacher ratings = .63). CONCLUSIONS: Parent reports are as sensitive as teacher reports in assessing the efficacy of long-acting pharmacologic treatment for ADHD in children during clinical trials using the nonstimulant atomoxetine.

Adolescent↗
PubMed2006

Effects of parental anxiety disorders in children at high risk for panic disorder: a controlled study.

BACKGROUND: To examine the association between anxiety disorders in parents and offspring in a sample of children at risk for panic disorder. We hypothesized that individual anxiety disorders will breed true in offspring. METHODS: Comparisons were made between offspring of parents with PD+MD (N=136), PD (N=27), MD (N=27), and Controls (N=103). All subjects were assessed with structured diagnostic interviews. Individual anxiety disorders in the offspring were used as dependent variables in logistic regression models where parental PD status, parental MD, and the same parental anxiety diagnosis were used as independent binary variables. RESULTS: Social phobia and separation anxiety disorder in the offspring were accounted for by the same disorders in the parent, whereas agoraphobia and OCD in the offspring were accounted for by parental panic disorder. CONCLUSIONS: These findings suggest that differing risk factors underlie the expression of individual anxiety disorders in children at risk for panic disorder.

Adolescent↗
PubMed2006

Psychopathology in females with attention-deficit/hyperactivity disorder: a controlled, five-year prospective study.

BACKGROUND: Despite the importance of understanding the long-term outcome of children with attention-deficit/hyperactivity disorder (ADHD), the available literature is predominantly based on male samples. This study estimated the lifetime burden of comorbid psychopathology in a large sample of girls with and without ADHD followed up over five years. METHODS: We conducted a blind, five-year prospective longitudinal study of girls with (n=140) and without (n=122) ADHD, aged 6-18 years at baseline, consecutively ascertained from either community pediatricians or psychiatrists at an academic medical center. At the five-year follow-up, 123 (88%) and 112 (92%) of the ADHD and control children, respectively, were re-assessed at a mean age of 16.7 years. Psychiatric disorders were assessed using blinded structured diagnostic interviews. RESULTS: At follow-up, females with ADHD were at significantly higher risk than controls to manifest disruptive behavior, mood and anxiety disorders, and substance dependence. The magnitude of increased risk was greatest for major depression and oppositional-defiant disorder, followed by substance dependence and anxiety disorders. CONCLUSIONS: These prospective follow-up findings documenting high morbidity associated with ADHD extend to females previously reported findings in male samples and underscore the importance of early recognition and intervention efforts for youth with ADHD of both genders.

Adolescent↗
PubMed2006

A controlled longitudinal 5-year follow-up study of children at high and low risk for panic disorder and major depression.

BACKGROUND: To evaluate the longitudinal course of psychiatric disorders in children of parents with panic disorder (PD) and major depression (MD) as they transition through the period of risk from childhood into adolescence. METHOD: Over a 5-year follow-up, we compared psychiatric disorders in four groups of children: (1) offspring of parents with PD plus MD (n=136); (2) offspring of parents with PD without MD (n=27); (3) offspring of parents with MD but without PD (n=53); and (4) offspring of non-PD non-MD parents (n=103). RESULTS: Parental PD was significantly associated with increased risk for anxiety disorders, irrespective of parental MD. Parental MD was associated with increased risk for MD, disruptive behavior disorders, and deficits in psychosocial functioning, irrespective of parental PD. CONCLUSIONS: These longitudinal findings confirm and extend previous cross-sectional results documenting significant associations between PD and MD in parents and patterns of psychopathology and dysfunction in their offspring.

Adolescent↗
PubMed2006

Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene.

OBJECTIVE: To determine whether SNPs within the dopamine transporter gene (DAT) are associated with quantitative phenotypes generated from drug frequency variables in an ADHD sample. METHOD: 35 SNPs were genotyped in and around DAT. We developed a quantitative phenotype at each SNP by weighting the drug frequency variables. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, a screening procedure was used to select and test the SNPs with the greatest power to detect an association in DAT. RESULTS: No SNPs in DAT were associated with the quantitative phenotypes generated from the drug frequency variables after the multiple comparisons adjustment; however, some SNPs achieved nominal significance. A sliding window of analysis of 3 SNPs also resulted in only nominal associations. CONCLUSIONS: SNPs in DAT do not appear to be associated with the phenotypes generated from drug frequency variables among individuals with ADHD.

Adolescent↗