Effects of source of DNA on genotyping success rates and allele percentages in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

Objective: In children diagnosed with attention-deficit/hyperactivity disorder (ADHD) and their parents, who were participants of the Preschool ADHD Treatment Study (PATS), we assessed the effect of source of DNA (from buccal or blood cells) on the genotyping success rate and allele percentages for the five polymorphisms in three candidate genes (DAT1, DRD4, and SNAP 25) investigated in the PATS pharmacogenetic study of response to stimulant medication.

Method: At baseline assessment, 241 individuals (113 probands and 128 parents) consented to participate; 144 individuals (52 probands and 92 parents) provided blood samples from venipuncture, and 97 individuals (61 probands and 36 parents) provided buccal samples from cheek swab as specimens for isolation of DNA. Three types of polymorphisms-variable number of tandem repeat (VNTR) polymorphism, tandem duplication polymorphism (TDP), and single nucleotide polymorphism (SNP)-were evaluated, including the DRD4 gene 48-bp VNTR in exon III, the DAT1 gene 40-bp VNTR in 3'-untranslated region, the DRD4 gene TDP 120-bp duplication in the promoter region, the SNAP-25 gene TC-1069 SNP, and the SNAP-25 gene TG-1065 SNP.

Factor structure of parent- and teacher-rated attention-deficit/hyperactivity disorder symptoms in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

Objective: This study examines one-, two-, and three-factor models of attention-deficit/hyperactivity disorder (ADHD) using the existing 18 Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV) symptoms in a sample of symptomatic preschoolers.

Methods: Parent and/or teacher ratings of DSM-IV symptoms were obtained for 532 children (aged 3-5.5) who were screened for the Preschool ADHD Treatment Study (PATS).

Parent versus teacher ratings of attention-deficit/hyperactivity disorder symptoms in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

Objective: To assess parent-teacher concordance on ratings of DSM-IV symptoms of attention-deficit/hyperactivity disorder (ADHD) in a sample of preschool children referred for an ADHD treatment study.

Methods: Parent and teacher symptom ratings were compared for 452 children aged 3-5 years. Agreement was calculated using Pearson correlations, Cohen's kappa, and conditional probabilities.

Effectiveness of methylphenidate in the 10-month continuation phase of the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

Objective: The aim of this study was to examine immediate-release methylphenidate effectiveness during the 10-month open-label continuation phase of the Preschoolers with Attention-Deficit/Hyperactivity Disorder (ADHD) Treatment Study (PATS).

Methods: One hundred and forty preschoolers with ADHD, who had improved with acute immediate-release methylphenidate (IR-MPH) treatment, entered a 10-month, open-label medication maintenance at six sites. Assessments included the Clinical Global Impression-Severity (CGI-S), CGI-Improvement (CGI-I), Children's Global Assessment Scale (C-GAS), Swanson, Nolan, and Pelham Questionnaire (SNAP), Scale Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale, Social Skills Rating System (SSRS), and Parenting Stress Index-Short Form (PSI-SF).

Methylphenidate effects on functional outcomes in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

Objective: The purpose of this study was to examine the effects of methylphenidate (MPH) on functional outcomes, including children's social skills, classroom behavior, emotional status, and parenting stress, during the 4-week, double-blind placebo controlled phase of the Preschoolers with Attention Deficit/Hyperactivity Disorder (ADHD) Treatment Study (PATS).

Methods: A total of 114 preschoolers who had improved with acute MPH treatment, were randomized to their best MPH dose (M = 14.22 mg/day; n = 63) or placebo (PL; n = 51).

Comorbidity moderates response to methylphenidate in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

Objective: The aim of this study was to examine whether demographic or pretreatment clinical and social characteristics influenced the response to methylphenidate (MPH) in the Preschoolers with ADHD Treatment Study (PATS).

Methods: Exploratory moderator analyses were conducted on the efficacy data from the PATS 5-week, double-blind, placebo-controlled six-site titration trial. Children (N = 165, age 3-5.

Clinical presentation of attention-deficit/hyperactivity disorder in preschool children: the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).

Objective: The aim of this study was to describe the clinical presentation of preschoolers diagnosed with moderate to severe attention-deficit/hyperactivity disorder (ADHD) recruited for the multisite Preschool ADHD Treatment Study (PATS). The diagnosis and evaluation process will also be described.

Method: A comprehensive multidimensional, multi-informant assessment protocol was implemented including the semistructured PATS Diagnostic Interview.

Atomoxetine treatment of ADHD in children with comorbid Tourette syndrome.

Objective: This study examines changes in severity of tics and ADHD during atomoxetine treatment in ADHD patients with Tourette syndrome (TS).

Method: Subjects (7-17 years old) with ADHD (Diagnostic and Statistical Manual of Mental Disorders, DSM-IV) and TS were randomly assigned to double-blind treatment with placebo (n = 56) or atomoxetine (0.5-1.

Neurocognitive correlates of child obsessive compulsive disorder and Tourette syndrome.

This study investigated the neurocognitive correlates of childhood OCD and TS, which are purported to share frontal-striatal dysfunction. Neurocognitive measures tapping frontal-striatal functions such as executive, attention/memory, and visuomotor abilities were administered to three groups of participants, OCD without comorbid TS (OCD), TS without comorbid OCD (TS), and normal controls. Results suggested that OCD group demonstrated deficits in the area of spatial attention relative to healthy controls.

Parent-rated anxiety symptoms in children with pervasive developmental disorders: frequency and association with core autism symptoms and cognitive functioning.

Background: In addition to the core symptoms, children with Pervasive Developmental Disorders (PDD) often exhibit other problem behaviors such as aggression, hyperactivity, and anxiety, which can contribute to overall impairment and, therefore, become the focus of clinical attention. Limited data are available on the prevalence of anxiety in these children. We examined frequency and correlates of parent-rated anxiety symptoms in a large sample of children with PDD.

Immunological validation of the EpitOptimizer program for streamlined design of heteroclitic epitopes.

One strategy to generate T-cell responses to tumors is to alter subdominant epitopes through substitution of amino acids that are optimal anchors for specific MHC molecules, termed heteroclitic epitopes. This approach is manually error-prone and time-consuming. In here, we describe a computer-based algorithm (EpitOptimizer) for the streamlined design of heteroclitic epitopes.

Atypical brain activation during simple & complex levels of processing in adult ADHD: an fMRI study.

Objective: Executive dysfunction in ADHD is well supported. However, recent studies suggest that more fundamental impairments may be contributing. We assessed brain function in adults with ADHD during simple and complex forms of processing.

Demographic and clinical characteristics associated with treatment status in family members with obsessive-compulsive disorder.

This study investigated the demographic and clinical factors that influence treatment status in family members with obsessive compulsive disorder (OCD). Six hundred and two subjects from the OCD Collaborative Genetics Study were interviewed using the Structured Clinical Interview for DSM-IV (SCID) to diagnose Axis I disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for assessment of OCD symptoms. The demographic and clinical data were compared between subjects who had received treatment and those who had not.

Significant linkage to compulsive hoarding on chromosome 14 in families with obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study.

Objective: Individuals with obsessive-compulsive disorder (OCD) who have compulsive hoarding behavior are clinically different from other OCD-affected individuals. The objective of this study was to determine whether there are chromosomal regions specifically linked to compulsive hoarding behavior in families with obsessive-compulsive disorder.

Methods: The authors used multipoint allele-sharing methods to assess for linkage in 219 multiplex OCD families collected as part of the OCD Collaborative Genetics Study.

Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures.

Background: Methylphenidate has been shown elsewhere to improve hyperactivity in about half of treated children who have pervasive developmental disorders (PDD) and significant hyperactive-inattentive symptoms. We present secondary analyses to better define the scope of effects of methylphenidate on symptoms that define attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), as well as the core autistic symptom domain of repetitive behavior.

Methods: Sixty-six children (mean age 7.

CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD.

Background: Atomoxetine, a selective norepinephrine reuptake inhibitor effective in the treatment of attention-deficit/hyperactivity disorder (ADHD), is metabolized through the cytochrome P-450 2D6 (CYP2D6) enzyme pathway, which is genetically polymorphic in humans. Variations in plasma atomoxetine exposures can occur because of genetic variation or as a consequence of coadministration with drugs that inhibit CYP2D6.

Method: We examined the effects of CYP2D6 on the efficacy, safety, and tolerability of atomoxetine in children and adolescents using pooled data from atomoxetine clinical trials.

Dietary status and impact of risperidone on nutritional balance in children with autism: a pilot study.

Background: Risperidone may be effective in improving tantrums, aggression, or self-injurious behaviour in children with autism, but often leads to weight gain.

Method: Using a quantitative Food Frequency Questionnaire (FFQ), we prospectively examined the nutritional intake of 20 children with autism participating in a randomised placebo-controlled trial of risperidone for disruptive behaviours.

Results: At baseline, the mean intakes for macronutrients, vitamins and minerals exceeded Dietary Reference Intakes (DRIs).

The association of DRD4 and novelty seeking is found in a nonhuman primate model.

Objective: The association of novelty seeking with a repeat polymorphism in the coding region of the dopamine D4 receptor gene (DRD4) has been demonstrated in several human populations, but not in others. The objective of this study was to test the generality of the association in a captive nonhuman primate population of known history, using objective methods for assessing novelty seeking and a pedigree-based association design.

Methods: Four hundred and fifty two socially-living vervet monkeys (Cercopithecus aethiops) from a large multigenerational pedigree at the UCLA-VA Vervet Research Colony were studied.

Parent satisfaction in a multi-site acute trial of risperidone in children with autism: a social validity study.

Rationale: Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures. Designing studies that consider the consumer's perspective will help to forge a better alliance between participants and researchers.

Objective: Participant satisfaction is seldom assessed in pharmacological research.

Direct health care costs for children with pervasive developmental disorders: 1996-2002.

We compared direct costs of treatment of Pervasive Developmental Disorder (PDD), asthma, and diabetes in children aged 3-17 years. A retrospective, claims-based study was conducted using the California Medicaid (Medi-Cal) database (1996-2002). Seven hundred and thirty-one children with PDD were identified and matched for sex with an equal number of randomly selected children with asthma and diabetes.

A prospective open trial of guanfacine in children with pervasive developmental disorders.

Objective: A common complaint for children with pervasive developmental disorder (PDD) is hyperactivity. The purpose of this pilot study was to gather preliminary information on the efficacy of guanfacine in children with PDD and hyperactivity.

Methods: Children with PDD accompanied by hyperactivity entered the open-label trial if there was a recent history of failed treatment with methylphenidate or the child did not improve on methylphenidate in a multisite, placebo-controlled trial.

Safety and tolerability of methylphenidate in preschool children with ADHD.

Objective: To report on the safety and tolerability of methylphenidate (MPH) 3- to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD) during 1 year of treatment.

Method: Exactly 183 children (3-5 years old) entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n=183); a 5-week placebo-controlled, double-blind phase (n=165); a 5-week double-blind, parallel phase (n=114); and 10 months of open-label maintenance (n=140 entered, 95 completed). Mean total daily MPH doses rose from the titration trial best dose, 14.

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

Background: Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions.

Methods: Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales.

Pharmacogenetics of methylphenidate response in preschoolers with ADHD.

Objective: The authors explored genetic moderators of symptom reduction and side effects in methylphenidate-treated preschool-age children diagnosed with attention-deficit/hyperactivity disorder (ADHD).

Method: DNA was isolated from 81 subjects in a double-blind, placebo-controlled, crossover methylphenidate titration. Parents and teachers completed ADHD symptom scales and side effect ratings for each of five randomly administered weekly conditions that included immediate-release methylphenidate 1.

Rationale, design, and methods of the Preschool ADHD Treatment Study (PATS).

Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS).

Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with attention-deficit/hyperactivity disorder (ADHD). Three hundred three subjects ages 3 to 5.