Faculty Bibliography

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). RESULTS: For the 95 children who completed the 10-month treatment, improvement occurred on the CGI-S (p = 0.02), CGI-I (p < 0.01), C-GAS (p = 0.001), and SSRS (p = 0.01). SNAP and SWAN scores remained stable. Forty five children discontinued: 7 for adverse effects, 7 for behavior worsening, 7 for switching to long-acting stimulants, 3 for inadequate benefit, and 21 for other reasons. The mean MPH dose increased from 14.04 mg/day +/- SD 7.57 (0.71 +/- 0.38 mg/kg per day) at month 1 to 19.98 mg/day +/- 9.56 (0.92 +/- 0.40 mg/kg per day) at month 10. CONCLUSIONS: With careful monitoring and gradual medication dose increase, most preschoolers with ADHD maintained improvement during long-term IR-MPH treatment. There was substantial variability in effective and tolerated dosing

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. Parent and teacher-report measures were used to supplement information from interviews. Consensus agreement by a cross-site panel on each participant's diagnoses was required. Analyses were conducted to describe the sample and to test associations between ADHD severity and demographic and clinical variables. RESULTS: The assessment protocol identified 303 preschoolers (3-5.5 years) with moderate to severe ADHD Hyperactive/Impulsive or Combined type. The majority of participants (n = 211, 69.6%) experienced co-morbid disorders, with oppositional defiant disorder, communication disorders, and anxiety disorders being the most common. Participants with co-morbid communication disorders were found to be more anxious and depressed. ADHD severity was found to correlate with more internalizing difficulties and lower functioning. Although boys and girls had similar symptom presentations, younger children had significantly higher ADHD severity. CONCLUSIONS: Preschoolers with moderate to severe ADHD experience high co-morbidity and impairment, which have implications for both assessment and treatment

The Predominantly Inattentive (PI) and Combined (CB) subtypes of AD/HD differ in cognitive tempo, age of onset, gender ratio, and comorbidity, yet a differentiating endophenotype has not been identified. The aim of this study was to test rigorously diagnosed PI, CB, and typical children on measures selected for their potential to reveal hypothesized differences between the subtypes in specific neurocognitive systems (anterior vs. posterior attentional systems) and processes (arousal vs. activation). Thirty-four CB and 26 PI children meeting full DSM-IV criteria for subtype both in school and at home, without confounding reading disability or emotional disorder, were enrolled along with 20 typically developing children. Neurocognitive functions measured included attention, inhibitory control, working memory, learning, and executive functions. Tasks included the Stroop, Wisconsin Card Sorting Test, Continuous Performance Test (CPT). Buschke Selective Reminding Test, ad the Tower of London (TOL), as well as instruments developed by Posner and Sternberg, and tasks assessing the impact on reaction time of [corrected] varying preparatory intervals and stimulus/response complexity. After co-varying for IQ, subtypes differed primarily on measures of impulsivity during tests of vigilance (CPT) and executive function (TOL), with the CB group showing greater impulsivity than both other groups. In addition, the PI group showed worse performance than CB and control groups on the WISC-III Processing Speed Index. Whether analyzed with or without an IQ co-variate, there was no support in the data for hypothesized differences between subtypes in functioning of the anterior vs. posterior attentional systems, nor in involvement of arousal vs. activation processes. The results indicate that the PI and CB subtypes are best differentiated by ratings, observations and tests of cognitive tempo and behavioral impulsivity. Neuropsychological methods have yet to identify critical neuropsychological [corrected] substrates of these differences.

BACKGROUND: The appropriateness of the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) nosology for classifying preschool mental health disturbances continues to be debated. To inform this debate, we investigate whether preschool psychopathology shows differentiation along diagnostically specific lines when DSM-IV symptoms are aggregated statistically. METHODS: One thousand seventy-three parents of preschoolers aged 2-5 years attending a large pediatric clinic completed the Child Behavior Checklist 1.5-5. A stratified probability sample of 193 parents of high scorers and 114 parents of low scorers were interviewed with the Preschool Age Psychiatric Assessment (PAPA). Confirmatory factor analysis was performed on symptoms from seven DSM disorders. RESULTS: Comparison of competing models supported the differentiation of emotional syndromes into three factors: social phobia (SOC), separation anxiety (SAD), and depression/generalized anxiety (MDD/GAD), and the differentiation of disruptive syndromes into three factors: oppositional defiant/conduct syndrome (ODD/CD), hyperactivity/impulsivity, and inattention. Latent syndrome correlations were moderately high after accounting for symptom overlap and measurement error. CONCLUSIONS: Psychopathology appears to be differentiated among preschoolers much as it is among older children, and adolescents. We conclude that it is as reasonable to apply the DSM-IV nosology to preschoolers as it is to apply it to older individuals.

OBJECTIVE: This article presents fidelity outcomes for five evidence-based practices that were implemented in routine public mental health settings in the National Implementing Evidence-Based Practices Project. METHODS: Over a two-year period 53 community mental health centers across eight states implemented one of five evidence-based practices: supported employment, assertive community treatment, integrated dual disorders treatment, family psychoeducation, and illness management and recovery. An intervention model of practice dissemination guided the implementation. Each site used both human resources (consultant-trainers) and material resource (toolkits) to aid practice implementation and to facilitate organizational changes. External assessors rated fidelity to the evidence-based practice model every six months from baseline to two years. RESULTS: More than half of the sites (29 of 53, or 55%) showed high-fidelity implementation at the end of two years. Significant differences in fidelity emerged by evidence-based practice. Supported employment and assertive community treatment had higher fidelity scores at baseline and across time. Illness management and recovery and integrated dual disorders treatment had lower scores on average throughout. In general, evidence-based practices showed an increase in fidelity from baseline to 12 months, with scores leveling off between 12 and 24 months. CONCLUSIONS: Most mental health centers implemented these evidence-based practices with moderate to high fidelity. The critical time period for implementation was approximately 12 months, after which few gains were made, although sites sustained their attained levels of evidence-based practice fidelity for another year.

The Child and Adolescent Trauma Treatments and Services Consortium (CATS) was the largest youth trauma project associated with the September 11 World Trade Center disaster. CATS was created as a collaborative project involving New York State policymakers; academic scientists; clinical treatment developers; and routine practicing clinicians, supervisors, and administrators. The CATS project was established to deliver evidence-based cognitive-behavioral trauma treatments for children and adolescents affected by the September 11 terrorist attack in New York City and to examine implementation processes and outcomes associated with delivery of these treatments. Referrals were obtained on 1,764 children and adolescents; of these, 1,387 were subsequently assessed with a standardized clinical battery and 704 found to be eligible for services. Ultimately 700 youth participated in the project. Treatments were delivered in either school or clinic settings by clinicians employed in 9 provider organizations in New York City. All participating clinicians were trained on the cognitive behavioral therapy models by the treatment developers and received case consultation for 18 months by expert clinician consultants and the treatment developers. The challenges of mounting a large trauma treatment project within routine clinical practices in the aftermath of a disaster and simultaneously evaluating the project have been significant. We outline the major challenges, describe strategies we employed to address them, and make recommendations based on critical lessons learned

Ca(2+) release from intracellular stores is controlled by complex interactions between multiple proteins. Triadin is a transmembrane glycoprotein of the junctional sarcoplasmic reticulum of striated muscle that interacts with both calsequestrin and the type 1 ryanodine receptor (RyR1) to communicate changes in luminal Ca(2+) to the release machinery. However, the potential impact of the triadin association with RyR1 in skeletal muscle excitation-contraction coupling remains elusive. Here we show that triadin binding to RyR1 is critically important for rapid Ca(2+) release during excitation-contraction coupling. To assess the functional impact of the triadin-RyR1 interaction, we expressed RyR1 mutants in which one or more of three negatively charged residues (D4878, D4907, and E4908) in the terminal RyR1 intraluminal loop were mutated to alanines in RyR1-null (dyspedic) myotubes. Coimmunoprecipitation revealed that triadin, but not junctin, binding to RyR1 was abolished in the triple (D4878A/D4907A/E4908A) mutant and one of the double (D4907A/E4908A) mutants, partially reduced in the D4878A/D4907A double mutant, but not affected by either individual (D4878A, D4907A, E4908A) mutations or the D4878A/E4908A double mutation. Functional studies revealed that the rate of voltage- and ligand-gated SR Ca(2+) release were reduced in proportion to the degree of interruption in triadin binding. Ryanodine binding, single channel recording, and calcium release experiments conducted on WT and triple mutant channels in the absence of triadin demonstrated that the luminal loop mutations do not directly alter RyR1 function. These findings demonstrate that junctin and triadin bind to different sites on RyR1 and that triadin plays an important role in ensuring rapid Ca(2+) release during excitation-contraction coupling in skeletal muscle.

BACKGROUND: Attaining a developmentally sensitive nosology for preschool disruptive behavior requires characterization of the features that distinguish it from the normative misbehavior of this developmental period. We hypothesize that quality of behavior and its pervasiveness across contexts are critical dimensions for clinical discrimination in young children and propose that structured diagnostic observation provides a systematic method for their identification. We use the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) to examine whether: (a) observed quality and pervasiveness of behavior distinguishes preschoolers with clinically concerning disruptive behavior from typically developing preschoolers, and (b) observed pattern of clinically salient behavior predicts impairment above and beyond maternal report of behavioral frequency. METHODS: Participants are a behaviorally heterogeneous sample of preschoolers (N = 327). Diagnostic methods developed for clinical assessment of preschoolers were used to classify children as (a) Non-Disruptive, (b) Sub-Clinical, or (c) Disruptive. Child behavior was coded based on interactions with parent and examiner during the DB-DOS. RESULTS: Quality and pervasiveness of observed behaviors during the DB-DOS significantly distinguished the three behavioral groups. Discriminative utility varied depending on the comparison. With few exceptions, clinically concerning patterns on the DB-DOS added significant incremental utility in predicting impairment. CONCLUSIONS: Observed patterns of clinically salient behavior show promise for advancing developmentally-informed characterization of disruptive behavior within the preschool period