Kaiser Permanente Autism Family Biobank
Kaiser Permanente Autism Family Biobank
This project involves sending 3,751 DNA samples from the KP Autism Family Biobank to Mount Sinai School of Medicine to perform whole exome and whole genome sequencing.
Funder: Mount Sinai School of Medicine
Investigator: Croen, Lisa
Funder: Mount Sinai School of Medicine
GEARs Combining advances in Genomics and Environmental science to accelerate Actionable Research and practice in ASD
The Autism Centers of Excellence (ACE) program is a trans-NIH initiative that supports large-scale studies on autism spectrum disorder. A priority area for the ACE program is work that will advance our understanding of the biologic mechanisms underlying gene-environment interplay in autism. We intend to create a research consortium with infrastructure to enable the investigation of the interplay of environmental risks with genetic discoveries at scale; build infrastructure for experimental testing of functional biologic impacts of gene-environment interaction; and develop and implement a pipeline for dissemination of findings for primary and secondary prevention efforts.
Investigator: Croen, Lisa
Funder: National Institute of Environmental Health Sciences
Prenatal medication exposure in autism, birth complications and developmental disabilities
Systematically investigate the effects of maternal medication use in pregnancy on offspring autism spectrum disorder (ASD) risk. Test the mechanisms underlying the associations between maternal medication use and ASD. Establish the specificity and generalizability of maternal medication effects on ASD.
Investigator: Croen, Lisa
Funder: National Institute of Child Health and Human Development
SEED Follow-Up Study
SEED is a case-control study comparing children aged 2-5 years with autism spectrum disorder to children with other developmental disabilities. The SEED Follow-up Study is a longitudinal study designed to improve understanding of risk factors and expression of autism spectrum disorder from childhood through early adulthood. This study will help us better understand how adolescents and young adults with autism spectrum disorder differ from those with other developmental disabilities or from the general population in terms of: 1) Health service needs and utilization, community and social supports, bullying and discrimination, safety and suicide, family and financial impacts, and independence and adaptive behavior; 2) Other outcomes relevant to child age (e.g., planning for exit from high school and vocational training); 3) Self-report of various aspects relevant to relationships and quality of life in adolescence and early adulthood.
Investigator: Croen, Lisa
Funder: Centers for Disease Control and Prevention
Maternal Health in Pregnancy and Autism Risk – Genetic and Non-genetic Mechanisms
This study will systematically identify maternal diagnoses in pregnancy associated with autism spectrum disorder (ASD) in offspring; test if the association between maternal diagnoses and ASD is due to shared genetic factors using family data; and test the association between maternal diagnoses in pregnancy and child’s genetic liability for ASD.
Investigator: Croen, Lisa
Funder: National Institute of Mental Health
Autism Specific Patterns of DNA Methylation from Birth to Age 5
This study will examine potential differences in DNA methylation (DNAm) in early life, from birth through age 5, between children who are ultimately diagnosed with autism spectrum disorder and those typically developing. Results from this work will inform whether a large-scale effort for evaluating longitudinal DNAm and epigenetic clock changes in ASD is necessary.
Investigator: Croen, Lisa
Funder: National Institute of Child Health and Human Development
Autism Intervention Research Network on Physical Health
Establish an interdisciplinary Autism Intervention Research Network on Physical Health node that will lead, promote, and coordinate national research activities to improve the physical health and well-being of individuals with autism spectrum disorder across the lifespan, including children and adolescents as they transition to adulthood. The focus of this node is gender, sexuality, and reproductive health of autistic adults.
Projects include needs assessments, design of multi-site intervention research studies, small grants funding to facilitate training and mentorship to diverse new investigators, and publication of annual research supplement.
Investigator: Croen, Lisa
Funder: Health Resources and Services Administration
Interactions of Environmental Chemical Mixtures, Genetics, and Immune Pathways in Autism Spectrum Disorder
The goal of this K99/R00 Pathway to Independence Award is to receive mentored training in polygenic GWAS tools and complex mixtures modeling to position my career toward understanding the roles of GxE interactions and immune disruption in the etiology of autism spectrum disorder(ASD). This research will examine the interplay of cumulative exposure to endocrine-disrupting chemicals (EDCs), immune markers (cytokines/chemokines), and ASD; examine genetic (maternal and fetal) influences on mid-pregnancy circulating levels of EDCs; and combine K99 methodologic training in polygenic and complex mixtures tools to a study of GxE interactions in ASD. The K99 research will use data from the Early Markers for Autism study (EMA) with possible extension to the NIH ECHO or KPRB Birth Cohort studies during the R00 phase.
Investigator: Ames, Jennifer
Funder: National Institute of Environmental Health Sciences
Understanding Barriers to Reproductive Health Care among Women with Autism Spectrum Disorder
This project will examine both reproductive health disparities and OB/GYN health care gaps for 2300 adolescent and adult women with Autism Spectrum Disorder (ASD) receiving care at Kaiser Permanente Northern California, paying particular attention to differences across sociodemographic characteristics, co-occurring psychiatric and physical health conditions, and type and frequency of other interactions with the health care system. We will also characterize the epidemiology of pregnancy and obstetrics care utilization including frequency of recommended prenatal visits, screenings, and perinatal complications among women with ASD compared with a control sample of neurotypical women. Our findings will inform development of strategies for improving provider knowledge, care practices, and effective health care delivery for this vulnerable population.
Investigator: Ames, Jennifer
Funder: National Institute of Child Health and Human Development
Barriers to Obstetric/Gynecological Health Care for Women with Autism Spectrum Disorders
This study will identify the sociodemographic and health factors associated with low utilization of obstetrics/gynecology services among adult women with autism spectrum disorders and explore whether these women are at higher risk of adverse maternal and birth outcomes than women who do not have autism spectrum disorder.
Investigator: Ames, Jennifer
Funder: Northern California Community Benefit Programs
COVID-19 Response Grant
Adults with intellectual or developmental disabilities may be especially impacted by the ways the COVID-19 pandemic has led to drastic changes in usual daily routines and the way healthcare encounters have been transitioned to virtual (video, telephone) visits. This project will characterize healthcare utilization and health status among adults with autism spectrum disorders (ASD) during the COVID-19 pandemic, comparing to similar indices in the pre-COVID period. Among adults with chronic health conditions that require ongoing management (such as diabetes, heart disease, or mental health conditions), we will also compare healthcare utilization between adults with and without ASD.
Investigator: Croen, Lisa
Funder: Special Hope Foundation
Optimizing Social Communication Measurement with the Social Responsiveness Scale
This project aims to: 1) compare the psychometric characteristics (including distributional properties, agreement with gold-standard diagnostic measures, and sensitivity and specificity) of short versus full Social Responsiveness Scale (SRS) scores, using existing child SRS data from the Environmental influences on Child Health Outcomes (ECHO) study; 2) use existing SRS data in ECHO to compare the performance of short versus full SRS scores in analyses of established risk factors for autism spectrum disorder (gestational age and parental age), as well as in assessment of familiality of scores (previously established for the full scale) in cohorts with available parental scores; and 3) A) develop a computer-adaptive testing (CAT)-based SRS, and B) conduct a separate validation of the 16-item short form administered as a standalone questionnaire (rather than relying on short form scores derived from responses to the full SRS) and of the newly developed CAT-based SRS in separate clinical and general population samples of children aged 3 to 5 years.
Investigator: Croen, Lisa
Funder: National Institutes of Health, Office of the Director
Autism Adaptive Community-Based Treatment to Improve Outcomes Using Navigators (ACTION) Network
One of the greatest challenges in autism treatment is how to bridge the health care science-to-service gap and address disparities in access to evidence-based early intervention for children with autism spectrum disorder. This project will establish a new interdisciplinary network of eight institutions to blend implementation and clinical effectiveness research designs, with an overarching aim to study the individual and combined effects of three intervention components: 1) Infusing mobile technology for professional development and family education using the Autism Navigator collection of web-based courses and tools; 2) Engaging families to access resources and support when they first learn their child has autism spectrum disorder, using a brief engagement intervention by community healthcare workers as family navigators to accelerate access to care; and 3) Coaching families to embed evidence-based intervention strategies in everyday activities using the Early Social Interaction Parent Coaching model to improve outcomes for toddlers with autism spectrum disorder.
Investigator: Croen, Lisa
Funder: National Institutes of Health
Barriers to Health Care in a Latino Population with Autism Spectrum Disorder
This study will identify barriers to the use of recommended assessment, diagnostic, and treatment services among Latino children and adolescents with autism spectrum disorder. The study population will comprise Kaiser Permanente Northern California Latino members, and comparisons will be made between commercially insured versus federally insured (Medicaid) patients, and English versus Spanish speakers.
Investigator: Croen, Lisa; Gordon, Nancy
Funder: Northern California Community Benefit Programs
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
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: Ferrara, Assiamira; Croen, Lisa
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
