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Autism Research Program

Studies

Prenatal Exposure to Metals and Risk for Autism Spectrum Disorder in MARBLES and EARLI

The peri-conceptual and prenatal periods of gestation are the most likely window of susceptibility for ASD; thus, maternal exposures and maternal genetic susceptibility are critical targets of investigation. Maternal exposure to heavy metals has been recognized for many years as a cause of fetal harm, particularly neurodevelopmental. In this study, we combine two prospective, enriched risk, pregnancy cohorts with available pregnancy and birth biosamples for metals and genetic measurement, with early-life developmental phenotype data, with age 3 ASD diagnosis status assessed by ASD researchers, and enough outcomes to provide adequate power given the enriched design. Further, we consider the utility of epigenetic measures in the study of these environmental risk factors, given evidence of the susceptibility of DNA methylation changes from metals exposure and the potential role of DNA methylation as a mediator of ASD risk or as a post-natal biomarker of metals exposure.
Investigator: Croen, Lisa
Funder: National Institute of Environmental Health Sciences

Health System Integration of Tools to Improve Primary Care for Autistic Adults

The objective of this project is to use a CBPR approach to understand how to best integrate the AASPIRE Healthcare Toolkit, an online healthcare toolkit aimed at improving primary care services for autistic adults, into the KP Northern CA healthcare system as we prepare for the larger effectiveness-implementation trial. We will do so by achieving the following specific aims: 1) To determine how to integrate use of the toolkit into the Kaiser systems. 2) To assess the acceptability and feasibility of both the intervention and the research protocols. 3) To further explore potential mechanisms of action.
Investigator: Croen, Lisa
Funder: National Institute of Mental Health

Understanding Family Economic Impact of Chronic Child Health Conditions

This study will address an important knowledge gap by estimating financial and time costs for families of children with autism. We will recruit 1,500 families of children 3-17 years old from geographically and ethnically diverse integrated health systems: Kaiser Permanente Northwest, Kaiser Permanente Northern California, Kaiser Permanente Georgia, Kaiser Permanente Hawaii and the OCHIN network of federally qualified health plans. Using the Family Economic Impact Interview, we will follow participating families for one year to collect information on family costs and examine what factors contribute to these costs.
Investigator: Croen, Lisa
Funder: National Institute of Child Health and Human Development

Prenatal SSRI Exposure, Maternal and Child Genotype, and Autism Spectrum Disorders

The prevalence of Autism Spectrum Disorders (ASD) has increased rapidly over recent decades. Among many environmental exposures that have also increased in frequency is the use of anti-depressant medications during pregnancy. Approximately 10% of pregnant women are prescribed selective seratonin reuptake inhibitors (SSRIs) SSRIs and other anti-depressant medication cross the placenta and are secreted in breast milk, thus raising concerns about adverse effects on the fetus or infant. This study will expand upon previous findings of an association between prenatal SSRI exposure and autism risk by utilizing data and biospecimens already collected in the SEED study to explore main and joint effects of maternal antidepressant use, maternal psychiatric disease history, and maternal and child genetic susceptibility.
Investigator: Croen, Lisa
Funder: National Institute of Child Health and Human Development

Prospective Evaluation of Air Pollution, Cognition and Autism from Birth Onward

This study will examine the relationship between perinatal and early life air pollution exposure and early longitudinal measures of cognitive ability and ASD in two prospective samples - Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) and Early Autism Risk Longitudinal Investigation (EARLI). Aim 1 is to assign air pollutant exposure using geographic information systems (GIS) technology and novel biomarker measurements. Aim 2 is to examine the effect of air pollutant exposure on the trajectory of cognitive development. Aim 3 is to evaluate the effect of air pollution exposure on cross-sectional and longitudinal measures of autistic traits and ASD diagnoses.
Investigator: Croen, Lisa
Funder: National Institute of Environmental Health Sciences

Neurodevelopment of Cognitive Control in Autism: Adolescence to Young Adulthood

This study compares the developmental trajectory of behavioral measures of cognitive control from adolescence into young adulthood in typical individuals (TYP) and individuals with Autism Spectrum Disorder (ASD). We predict that approximately 2/3 of those with ASD will show a persistent lag in performance on cognitive control tasks through young adulthood, and that in those with ASD, cognitive control abilities will predict performance in complex information processing. We will also examine the development of the neural mechanisms of cognitive control from adolescence to young adulthood. We hypothesize that those with ASD will employ more reactive cognitive control than their TYP counterparts. Lastly, we will investigate relationships between the two modes of cognitive control, and functional and mental health outcomes between adolescence and young adulthood in the ASD group.
Investigator: Croen, Lisa
Funder: National Institute of Mental Health

Folic Acid Prevention Pathways for ASD in High Risk Families

Autism spectrum disorders affect 1 in 68 children in the US. There is evidence for a potentially large role for the early in-utero environment, including gestational nutrition, in ASD etiology. Maternal folic acid is one of the first modifiable factors with the potential to reduce occurrence of ASD. In addition to being essential for neurodevelopment, folate is a primary methyl-donor for methylation reactions. The time near conception is an especially critical period for adequate methyl supply during cycles of active de-methylation and re-methylation during embryogenesis, interactions with genetic and environmental risk factors, and the greatest reduction in ASD risk associated with higher maternal folic acid intake. Using data and samples from mother-child pairs in two large prospective studies, this study proposes to examine specific pathways for prevention of ASD through maternal dietary and supplemental folate intake.
Investigator: Croen, Lisa
Funder: National Institute of Environmental Health Sciences

Transitioning Pediatric Patients with ASD to Adult Care

This study includes the following aims: 1) Investigate prevalence of medical and psychiatric co-morbidities and rate of service and medication utilization among transition-age (15-25 years) patients with ASD in KPNC; 2) Determine barriers and facilitators of smooth transitions from pediatric to adult care; and 3) Develop and test tools and healthcare delivery processes to improve transitions from pediatric to adult care. Based on information collected in open-ended interviews and other appropriate modes, and on observations, we will collaborate with a multidisciplinary team of clinical providers, patients and caregivers to develop tools and resources and health care delivery processes that support a smooth transition from pediatric to adult care. The study is co-funded by Special Hope Foundation and Autism Speaks.
Investigator: Croen, Lisa
Funder: Autism Speaks

Design of study of fetal pharmaceutical use of the 1950s through 70s

This study will explore the feasibility of accessing information on the nature and extent of prenatal pharmaceutical usage in the late 1950s through the 1970s.
Investigator: Croen, Lisa
Funder: 

Early Life Exposure to Endocrine Disrupting Chemicals and Child Growth, Adiposity, and Neurodevelopment

We hypothesize that in-utero exposures to commonly used endocrine disrupting chemicals, such as PFCs and PBDEs, individually and/or in combination, have adverse effects on child obesity and neurodevelopment through possible common pathways. Our aims are: Aim 1. To evaluate whether in-utero exposures to maternal PFCs and PBDEs, individually and/or in combination, are associated with infant growth, adiposity and neurodevelopment. Aim 2. To evaluate whether in-utero PFCs and PBDEs exposures are associated with metabolic determinants of obesity and neurodevelopment . Aim 3. To explore whether in-utero PFCs and PBDEs exposures are associated with infant patterns of DNA methylation. Aim 4. To identify infant, maternal and paternal factors that modify the association of exposure to in-utero PFCs and PBDEs exposures and with infant growth, adiposity and neurodevelopment.
Investigator: Croen, Lisa; Ferrara, Assiamira
Funder: National Institutes of Health

Role of Pre-natal Vitamin D and Gene Interactions in Autism Spectrum Disorders: Leveraging an Existing Case-Control Study

This study is the first to investigate the role of perinatal vitamin D deficiency or insufficiency in ASD etiology, as modulated by race and genes involved in vitamin D metabolism and receptor activity, in a large, racially-diverse cohort. The role of vitamin D in a number of health conditions has gained recent attention, concurrent with high frequency of vitamin D deficiency/insufficiency being documented, attributed to changes in lifestyle. Evidence indicating higher risk of autism by factors shown to be related to lower vitamin D levels and recent advances in the understanding of the role of vitamin D on brain and immune function support a potential role in autism etiology that warrants rigorous investigation. A few studies of children with autism (or their mothers) have found lower vitamin D levels, but they all were limited by small samples and measurement of levels after the critical period of brain development.
Investigator: Croen, Lisa
Funder: National Institute of Child Health and Human Development

California CADDRE-SEED Phase II

The goal of this project is to continue the SEED study, a case-control study of genetic and environmental risk factors for autism. The major goal of the project is to conduct a multi-site collaborative epidemiologic study to investigate risk and causal factors for Autism Spectrum Disorders (ASD) and phenotypic subgroups of ASD using a population-based case-cohort study design.
Investigator: Croen, Lisa
Funder: Centers for Disease Control and Prevention