Faculty Bibliography

BACKGROUND AND PURPOSE: The early postnatal period is perhaps the most dynamic phase of white matter development. We hypothesized that the early postnatal development of the corpus callosum and corticospinal tracts could be studied in unsedated healthy neonates by using novel approaches to diffusion tensor imaging (DTI) and quantitative tractography. MATERIALS AND METHODS: Isotropic 2 x 2 x 2 mm(3) DTI and structural images were acquired from 47 healthy neonates. DTI and structural images were coregistered and fractional anisotropy (FA), mean diffusivity (MD), and normalized T1-weighted (T1W) and T2-weighted (T2W) signal intensities were determined in central midline and peripheral cortical regions of the white matter tracts of the genu and splenium of the corpus callosum and the central midbrain and peripheral cortical regions of the corticospinal tracts by using quantitative tractography. RESULTS: We observed that central regions exhibited lower MD, higher FA values, higher T1W intensity, and lower T2W intensity than peripheral cortical regions. As expected, MD decreased, FA increased, and T2W signal intensity decreased with increasing age in the genu and corticospinal tract, whereas there was no significant change in T1W signal intensity. The central midline region of the splenium fiber tract has a unique pattern, with no change in MD, FA, or T2W signal intensity with age, suggesting different growth trajectory compared with the other tracts. FA seems to be more dependent on tract organization, whereas MD seems to be more sensitive to myelination. CONCLUSIONS: Our novel approach may detect small regional differences and age-related changes in the corpus callosum and corticospinal white matter tracts in unsedated healthy neonates and may be used for future studies of pediatric brain disorders that affect developing white matter.

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

CONTEXT: Salivary cortisol levels during social challenge relate to adaptive functioning in children and adults. Low cortisol levels have been related to conduct problems and antisocial behavior. Although studies in rodents implicate early-life social experience in cortisol regulation, no studies with humans have examined the effects of an experimentally manipulated early-life social experience on cortisol regulation. OBJECTIVE: To examine the effects of experimental manipulations of social experience on cortisol response to a social challenge in preschoolers at risk for antisocial behavior. DESIGN: Randomized controlled trial. SETTING: Department of Child and Adolescent Psychiatry, New York University School of Medicine. PARTICIPANTS: Ninety-two preschool-age siblings of youths adjudicated for delinquent acts. Intervention Family-based intervention included 22 weekly group sessions for parents and preschoolers and 10 biweekly home visits conducted during a 6- to 8-month period. MAIN OUTCOME MEASURES: Salivary cortisol levels before and after a social challenge (entry into an unfamiliar peer group). RESULTS: Relative to controls, children in the intervention condition had increased cortisol levels in anticipation of the peer social challenge. Increases were relative to both preintervention cortisol levels during the challenge and cortisol levels in the home, which were not altered by the intervention. CONCLUSIONS: A family-based preventive intervention for children at high risk for antisocial behavior alters stress response in anticipation of a peer social challenge. The experimentally induced change in cortisol levels parallels patterns found in normally developing, low-risk children

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.

OBJECTIVE: To examine symptomatology and mental health service use following students' contact with a large urban school district's suicide prevention program. METHOD: In 2001 school district staff conducted telephone interviews with 95 randomly selected parents approximately 5 months following their child's contact with the district's suicide prevention program, a School Gatekeeper Training model. Parents provided information regarding service use, their child's depressive symptoms (using the Diagnostic Interview Schedule for Children Predictive Scale, Depression module), and their perceptions of their child's need for services. Information about the crisis intervention was abstracted from a standardized assessment form. RESULTS: More than two thirds of students received school or community mental health services following contact with the suicide prevention program. Depressive symptoms, but not past year suicide attempt, predicted community mental health service use. Latino students had lower rates of community mental health service use than non-Latinos. School-based service use did not differ by student characteristics including race/ethnicity. CONCLUSIONS: Most students identified by a school-based suicide prevention program received follow-up care, although Latinos were less likely to access services outside the school. School-based mental health services may be an important way in which underserved populations at risk of suicide can receive care.

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: 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

Perceived social-evaluative threat triggers the hypothalamic-pituitary adrenal (HPA) axis, resulting in cortisol release. The current study examined the effects of varying the levels of social-evaluative threat on the stress response. Sixty healthy men (mean age + 23.17 +/- 3.89 years) underwent a public speaking task. Four conditions were established on the basis of panel location (inside or outside the room) and number of panelists (one or two). It was hypothesized that these variations affect salivary cortisol and physiological responses in a gradient manner. The task elicited significant cortisol and blood pressure changes for all conditions, but no difference between the groups was found, suggesting that all conditions were equally stressful. Study conclusions were that, for men, the visual presence of a panel is not necessary to elicit a cortisol response. Furthermore, increasing the number of judges does not increase the intensity of the stress response in a gradual manner, but rather seems to follow a threshold pattern. Future studies should include women and try to define the possible threshold to activate the HPA axis

In 118 children followed from age 2 to 5 (59 with autism, 24 with PDD-NOS and 35 with non-spectrum developmental disabilities), age 2 and age 3 scores of non-verbal ability, receptive communication, expressive communication and socialization were compared as predictors of receptive and expressive language at age 5. Non-verbal cognitive ability at age 2 was generally the strongest predictor of age 5 language, while at age 3 communication scores were a stronger predictor of age 5 language for children with autism. Early joint attention as well as vocal and motor imitation skills were more impaired in children who did not develop language by age 5 (but had relatively strong non-verbal cognitive skills) than in children who did develop language by 5