Infection, fever and immunity and offspring ADHD in a population-based pregnancy/birth cohort

基于人群的妊娠/出生队列中的感染、发烧和免疫以及后代多动症

• 批准号: 9217203
• 负责人: MADY HORNIG
• 金额: $ 42.24万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9217203
• 关键词: 3 year old; Address; Affect; Alcohol or Other Drugs use; Allergic; Analgesics; Animal Model; Antibiotics; Antibody Response; Attention deficit hyperactivity disorder; Attenuated; Autoimmune Process; Biological; Biological Markers; Birth; Blood specimen; Brain; Breast Feeding; Child; Clinical; Clinical assessments; Cohort Studies; Collection; Comorbidity; Cytomegalovirus; Data; Development; Diet; Disease; Early Diagnosis; Early Intervention; Economic Burden; Environmental Exposure; Epidemiology; Event; Exposure to; Fathers; Fever; Funding; Genetic Predisposition to Disease; Heritability; Herpesvirus 1; Hypersensitivity; Immune; Immune System Diseases; Immune response; Immunity; Immunoassay; Immunology procedure; Immunoprecipitation; Individual; Individual Differences; Infant; Infection; Infectious Agent; Inflammatory; Inflammatory Response; Innate Immune Response; Intake; Intervention; Learning Disabilities; Life; Luciferases; Maternal antibody; Measures; Mediating; Mental disorders; Microbe; Micronutrients; Modeling; Mothers; Neuraxis; Neurodevelopmental Disability; Non-Steroidal Anti-Inflammatory Agents; Norway; Outcome; Pathogenesis; Pharmaceutical Preparations; Plasma; Pregnancy; Prevention; Preventive measure; Questionnaires; Registries; Reporting; Resources; Retrieval; Risk; Risk Factors; Role; Sample Size; Sampling; Serologic tests; Serological; Study models; Symptoms; System; Systems Development; Teratogens; Testing; Time; Toxoplasma gondii; Umbilical Cord Blood; United States; United States National Institutes of Health; Universities; Vitamin D; Zinc; adaptive immune response; antipyretic; cohort; data access; design; developmental disease; disorder control; disorder risk; epidemiological model; fighting; high throughput screening; immune activation; immunoregulation; influenzavirus; insight; neurogenesis; novel; offspring; pathogen; population based; postnatal; pregnant; prospective; psychosocial; public health relevance; synaptogenesis; systems research

ABSTRACT Growing evidence from epidemiologic, clinical and animal model studies of attention-deficit/hyperactivity disorder (ADHD) supports a role for pre- and postnatal immune and infectious factors in the pathogenesis of this common, disabling and frequently persistent disorder. ADHD is a major contributor to the psychosocial and economic burden of neurodevelopmental disabilities globally, affecting 5% of children in the United States, and is frequently complicated by comorbidity with substance use and other psychiatric disorders, learning disabilities and criminality. Associations of ADHD with exposure of mothers during pregnancy and infants in early life to specific pathogens and fever episodes are reported, but individual differences in innate and adaptive immune responses, and concomitant exposures to medications and immunity-regulating micronutrients, have not been rigorously and prospectively addressed. This project will leverage the unique data and biological sample resources of the Norwegian Mother and Child Cohort Study (MoBa) and the Center for Infection and Immunity at Columbia University for insights into the role of infection and immunity in ADHD through pursuit of three complementary aims that address not only maternally-reported infection, fever and immune/inflammatory disease but also quantitative measures of immune activation and pathogen-directed antibody responses. Because MoBa mothers report illness events and symptoms as well as medication use in 4-week intervals throughout pregnancy, unusually rich information is available to relate the timing of these phenomena, rather than gestation per se, to ADHD outcomes. In Aim 1 we will investigate the relationship of maternal and child infection, fever and immune disorders to ADHD risk using prospective MoBa questionnaire data, controlling for medication use (antipyretics, analgesics, antibiotics) and intake of micronutrients with immunomodulatory potential (vitamin D, zinc). In Aim 2 we will define the immune signatures in plasma from mothers and children during pregnancy and at birth and determine their association with ADHD risk using multiplexed immunoassays (Luminex) to compare levels of 60 immune/inflammatory molecules with known or suspected effects on neurogenesis and synaptogenesis broadly as well as ADHD-relevant dopaminergic circuitry more specifically. In Aim 3 we will examine the role of specific infectious agents implicated in ADHD by measuring maternal antibodies at mid-gestation and birth to ToRCH pathogens Toxoplasma gondii, rubellavirus, cytomegalovirus and herpes simplex viruses 1 and 2 using multiplexed immunoassays (Luminex) and to influenza viruses using luciferase immunoprecipitation systems (LIPS). In concert, these aims have the potential to identify novel factors and biomarkers for ADHD risk that could facilitate early diagnosis and intervention and guide the development of preventive measures.

摘要