The NeuroDevNet Autism Spectrum Disorders Demonstration Project

The NeuroDevNet Autism Spectrum Disorder Demonstration Project interfaces at many levels with the network's research themes and priorities. Our interdisciplinary team aims to improve understanding of genetic factors underlying vulnerability to autism spectrum disorders (ASDs) to develop better diagnostic strategies and, ultimately, to pinpoint molecular pathways relevant to developing biologically based treatments. Linking our existing longitudinal ASD cohorts with both genetics and neuroimaging studies will provide, for the first time, integrated data on how the genetic variation influences brain and behavioral development in ASD. Importantly, as our science progresses and we translate this information to the health care system, we will also educate policy makers, media, and business, so an informed society is prepared to capitalize on new genomic advances and effectively integrate these into health services for the broader community. We believe that this research has the potential to transform assessment and care for individuals with ASD.     

Spatially patterned gene expression for guided neurite extension

Axon pathfinding by localized expression of guidance molecules is critical for the proper development of the nervous system. In this report, we present a well-defined spatially patterned gene expression system to investigate neurite guidance in vitro. Nonviral gene delivery was patterned by combining substrate-mediated gene delivery with soft lithography techniques, and the amount of protein produced at the region of localized expression was varied by altering the vector concentration and the width of the pattern, highlighting the flexibility of the system. A neuronal coculture model was used to investigate responses to spatial patterns of nerve growth factor (NGF) expression. The soluble NGF gradient elicited a guidance cue, and the degree of guidance was governed by the distance a neuron was cultured from the pattern and the time between accessory cell and neuron seedings. A portion of the diffusible NGF bound to the culture surface in the extracellular space, and the surface-associated NGF supported neuron survival and neurite outgrowth. However, the surface-bound NGF gradient alone did not elicit a guidance signal, and in fact masked the guidance cue by soluble NGF gradients. Mathematical modeling of NGF diffusion was used to predict the concentration gradients, and both the absolute and fractional gradients capable of guiding neurites produced by patterned gene expression differed substantially from the values obtained with existing engineered protein gradients. Spatially patterned gene expression provides a versatile tool to investigate the factors that may promote neurite guidance.     

Variations in use of second-generation antipsychotic medication by race among adult psychiatric patients

OBJECTIVE: This study examined variations in the use of second-generation antipsychotic medication among African-American and non-Hispanic white patients in a national sample of adults who were treated by psychiatrists. METHODS: This study used data from studies of psychiatric patients and treatments that were conducted by the American Psychiatric Institute for Research and Education's (APIRE's) Practice Research Network (PRN). Psychiatrists provided detailed clinical data for 126 African-American patients and 574 white patients who were randomly selected and for whom antipsychotic medications were prescribed. The study assessed differences by race in the use of second-generation antipsychotic medication, adjusting for clinical, sociodemographic, and health-system characteristics, including patients' source of payment for treatment. RESULTS: African-American patients were less likely than white patients to receive second-generation antipsychotic medications (49 percent compared with 66 percent). After the analysis statistically adjusted for clinical, sociodemographic, and health-system characteristics, African-American patients remained less likely than white patients to receive second-generation antipsychotics. CONCLUSIONS: Because African Americans tended to receive medications that are not first-line recommended treatments and that have a greater risk of producing tardive dyskinesia and extrapyramidal side effects, African Americans could be expected to suffer diminished clinical status. This disparity may also contribute to lower rates of adherence and to more frequent emergency department visits and psychiatric hospitalizations among African Americans     

Acute Adaptation to Volume Unloading of the Functional Single Ventricle in Children Undergoing Bidirectional Glenn Anastomosis

Objective. Volume unloading of the functional single ventricle after a bidirectional Glenn anastomosis (BDG) prior to 1 year of age leads to improved global ventricular function as measured by the myocardial performance index (MPI), a Doppler‐derived measurement of combined systolic and diastolic ventricular function. Systolic function remains unchanged after BDG according to previous studies; however, acute changes in global and diastolic function have not been previously investigated in this cohort. Our objective was to assess the short‐term effects of the BDG on global ventricular function in patients with a functional single ventricle. Design. Echocardiograms to obtain MPI, isovolumic contraction time, and isovolumic relaxation time were performed at four time periods: in the operating room, in the operating room prior to BDG, shortly after separation from cardiopulmonary bypass, less than 24 hours postoperatively, and either prior to hospital discharge or at the first clinic follow‐up visit. Results. Twenty‐six patients were enrolled. There was significant ventricular dysfunction noted shortly after separation from cardiopulmonary bypass, median MPI 0.63 (0.39–0.81), that persisted in the short term postoperatively median MPI 0.50 (0.40–0.63). Isovolumic contraction time did not change, however, isovolumic relaxation time was significantly prolonged following BDG. Conclusion. In the postoperative patient after BDG, systolic function is preserved; however, there is evidence of diastolic and global ventricular dysfunction, at least in the short term.     

The Impact of Realignment on Utilization and Cost of Community-Based Mental Health Services in California

Decentralization of California's public mental health system under program realignment has changed the utilization and cost of community-based mental health services. This study examined a sample of 75,951 users, representing 1.5 million adults who visited California's public mental health services during a 6-year period (FY 1988–1990 and FY 1992–1994). Regression analysis was performed to examine cost and utilization reduction over time, across regions, and across psychiatric diagnoses. Overall utilization and cost of community-based mental health services dropped significantly after the implementation of realignment. They were significantly lower for (a) 24-hour services in the urban industrialized Southern Region and (b) outpatient services in the agricultural Central Region of the state. Users diagnosed with mood disorders took a greater portion, but were associated with significantly less treatment and cost than other users in the post-realignment period. When local communities bear the financial risks and rewards, they find more efficient methods of delivering community-based mental health services.     

Acute lymphoblastic leukemia in the offspring of a mother exposed to diethylstilbestrol (DES) in utero. A case report and hypothesis

A case of a child with acute lymphoblastic leukemia (ALL) is reported. The child's mother was exposed to diethylstilbestrol (DES) in utero during the first two trimesters of pregnancy. Causal association for this child's leukemia could have resulted either from a maternal germ cell event or abnormal DES-induced intrauterine environment.     

Substitution in a Medicaid mental health carve-out: services and costs

The objective is to empirically test the incentives associated with a Medicaid capitated mental health carve-out contract, whether outpatient services (less expensive, inside the contract) and residential treatment center care (costly care, outside of the contract) were substituted for inpatient psychiatric hospitalization used by children and adolescents. Data sources include Medicaid fee-for-service (FFS) claims for the non-capitated comparison sites and for residential treatment center use, and "shadow billing" encounter data for the experimental capitated managed care sites that provided public mental health services for children and adolescents with Medicaid insurance statewide in Colorado from September 1994 to June 1997. Two part least squares regression models are used to decompose services. Managed care sites are compared to sites that remained under FFS financing, before and in two post-periods after the carve-out. Principal findings show that children and adolescents who received mental health services from a capitated managed care provider were significantly less likely to receive inpatient care, and significantly more likely to receive residential treatment center care. In addition, insurance contract design contains financial incentives that affect the amount and mix of clinical care provided to clients by risk-bearing provider agencies. Findings provide evidence of cost substitution from inpatient care both inside the specialty system and outside the carve-out to other child-serving systems.     

Two children with muscular dystrophies ascertained due to referral for diagnosis of autism

We report two children who were referred for diagnostic assessment for autism and were subsequently determined to have a muscular dystrophy (MD). Each child had a history of speech delay and social impairments, but also had motor delays that had not previously been investigated. Both children met diagnostic criteria for autism spectrum disorders on standardized assessment. Each child was hypotonic and had other mild motor impairments. Serum creatine kinase (CK) activity was markedly elevated in each child, and subsequent muscle biopsy led to diagnosis of Becker's MD and congenital (autosomal recessive) MD, respectively. These cases highlight the importance of a thorough neuromotor examination for all children with suspected autism spectrum disorders.