Faculty Bibliography

OBJECTIVE: Chest pain in children and adolescents is rarely associated with cardiac disease. We sought to examine psychological symptoms in youngsters with medically unexplained chest pain. We hypothesized that children and adolescents with medically unexplained chest pain would have high rates of anxiety and depressive symptoms. METHODS: We assessed 65 youngsters with noncardiac chest pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self-report measures of anxiety and depressive symptoms and anxiety sensitivity. RESULTS: Compared with the asymptomatic benign-murmur group, youngsters with NCCP had higher levels of some anxiety symptoms and anxiety sensitivity. Differences on depressive symptoms were not significant. CONCLUSIONS: Though preliminary, results suggest that youngsters with chest pain may experience increased levels of some psychological symptoms. Future studies of noncardiac chest pain in youngsters should include larger samples and comprehensive diagnostic assessments as well as long-term follow-up evaluations

Two-component systems represent the most widely used signaling paradigm in living organisms. Encoding the prototypical two-component system in Gram-positive bacteria, the staphylococcal agr (accessory gene regulator) operon uses a polytopic receptor, AgrC, activated by an autoinducing peptide (AIP), to coordinate quorum sensing with the global synthesis of virulence factors. The agr locus has undergone evolutionary divergence, resulting in the formation of several distinct inter- and intraspecies specificity groups, such that most cross-group AIP-receptor interactions are mutually inhibitory. We have exploited this natural diversity by constructing and analyzing AgrC chimeras generated by exchange of intradomain segments between receptors of different agr groups. Functional chimeras fell into three general classes: receptors with broadened specificity, receptors with tightened specificity, and receptors that lack activation specificity. Testing of these chimeric receptors against a battery of AIP analogs localized the primary ligand recognition site to the receptor distal subdomain and revealed that the AIPs bind primarily to a putative hydrophobic pocket in the receptor. This binding is mediated by a highly conserved hydrophobic patch on the AIPs and is an absolute requirement for interactions in self-activation and cross-inhibition of the receptors. It is suggested that this recognition scheme provides the fundamental basis for agr activation and interference

While it has been hypothesized that brain development is abnormal in schizophrenia and other neurodevelopmental disorders, there have been few attempts to study very early brain development in children. Twenty unsedated healthy newborns underwent 3 Tesla magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI). The left ventricle was significantly larger than the right; females had significantly larger ventricles than males. Fractional anisotropy (FA) increased significantly with gestational age in the genu and splenium of the corpus callosum. It is feasible to study brain development in unsedated newborns using 3 T MRI.

The objective of this study was to assess tic persistence and tic-associated impairment in referred youth with Tourette's Disorder (TD). Subjects were 50 youth (ages 6-17 years) who met DSM-IV diagnostic criteria for TD, were referred to a specialized TD program, and were evaluated by clinical and structured diagnostic interview. Tic severity and impairment was measured using the Yale Global Tic Severity Scale. The total tic score at or above minimal range defined tic persistence, and a TD impairment score at or above moderate range defined tic-associated impairment. Results were assessed during administration of the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiological Version. Mean age of onset of TD was 5.1 +/- 2.3 years, and mean illness duration was 5.6 +/- 3.2 years. At baseline, 88% of subjects met threshold criteria for at least mild tics, but only 30% met criteria for tic-associated impairment. At 2-year follow-up, 82% of these subjects met criteria for tic persistence (NS change from baseline), but only 14% met criteria for TD-associated impairment (p < .04 change from baseline). Although tics followed a persistent course in the majority of youth with TD, they were infrequently associated with impairment. There was a significant reduction in the proportion of youth with TD impairment from baseline to follow-up. These results support the view that TD is a persistent disorder, but suggest a dissociation between tic persistence and tic-associated dysfunction

The adult cerebral cortex can adapt to environmental change. Using monocular deprivation as a paradigm, we find that rapid experience-dependent plasticity exists even in the mature primary visual cortex. However, adult cortical plasticity differs from developmental plasticity in two important ways. First, the effect of adult, but not juvenile monocular deprivation is strongly suppressed by administration of barbiturate just prior to recording visual evoked potentials, suggesting that the effect of adult experience can be inactivated acutely. Second, the effect of deprivation is less persistent over time in adults than in juveniles. This correlates with the known decline in CREB function during maturation of the visual cortex. To compensate for this decline in CREB function, we expressed persistently active VP16-CREB and find that it causes adult plasticity to become persistent. These results suggest that in development and adulthood, the regulation of a trans-synaptic signaling pathway controls the adaptive potential of cortical circuits.

OBJECTIVE: To describe the psychometric properties and test the reliability of a new instrument designed to measure mental health services use within pediatric clinical samples, the Services for Children and Adolescents-Parent Interview (SCAPI), which was developed by the National Institute of Mental Health Multimodal Treatment Study of Children With Attention Deficit Hyperactivity Disorder (MTA). METHOD: Similarities and differences with other measures of services use are described. Ten types of services are measured by the SCAPI. Formal test-retest reliability testing was carried out in 104 subjects with a mean time between tests of 18 days. RESULTS: Test-retest kappa values ranged from 0.49 to 1.00, with an overall kappa value for all services of 0.97. Seven of the 10 service types had kappa values of 0.75 or higher, indicating excellent reliability. In addition, matched responses on specific questions about reasons for seeking services, starting and ending dates, number and length of visits, and type of provider seen were more than 75% for most service categories, consistently so for reporting of medications and school services. CONCLUSIONS: The SCAPI is a reliable instrument for assessing mental health and related services use and may be an especially valuable adjunct in studies involving clinical samples, especially clinical trials.

OBJECTIVE: To date, no instrument has been developed that captures children's services use across primary care, specialty mental health, and other settings, including setting, treatment type, provider discipline, and length and intensity of specific interventions over varying follow-up periods. The authors developed a highly structured services assessment measure [Services for Children and Adolescents-Parent Interview (SCAPI)] for use in the National Institute of Mental Health Multimodal Treatment Study of Children With Attention Deficit Hyperactivity Disorder (MTA). METHOD: After successfully piloting and refining the SCAPI during initial phases of the MTA, the authors used this measure at 24 months post-randomization to ascertain the previous 6 months of services use for all participating (516 of 579) MTA children and families and 285 age- and gender-matched classroom control children. RESULTS: Findings revealed meaningful, face-valid differences between MTA and control children in levels and types of services used during the previous 6-month period. Services use data reported by parents was substantially in accord with data independently gathered by the research data center. Site variations were found in the level and use of several specific services, such as individual child psychotherapy (sites ranged from 0% to 6.8% among classroom controls compared with 9.7% to 46.1% among MTA participants) and special education services (0% to 14.6% among classroom controls, 27.5% to 34.8% among MTA participants), consistent with differences reported in other studies. CONCLUSIONS: These data support the descriptive validity of SCAPI-ascertained services use data and indicate that the SCAPI can provide investigators and policymakers a valid means of assessing services type, intensity, onset and offset, provider type, and content.

The school nurse has a tremendous opportunity to be a part of the home, school, and community team in promoting state-of-the-art care for youngsters with ADHD. The multi-modal strategic approach, combining carefully titrated pharmacotherapy with these specific behavioral interventions in the child's school and other settings, currently provides the greatest likelihood of a positive treatment outcome for youth with ADHD