R01ES032028

The Influence of Multiple Environmental Exposures on Suicide Risk - Project Summary:

Suicide is the 10th leading cause of death in the United States, with the national economic costs of suicide approximated to be $53 billion annually. While suicide's causes are complex, suicide clusters in families, and it is widely hypothesized that interactions between an underlying genetic predisposition and environmental factors are in suicide's causal pathway.

We recently reported a heightened risk of suicide following short-term exposure to fine particulate matter and nitrogen dioxide among all suicides in Salt Lake County, Utah from 2000-2010. Complementary studies investigating the relationship between weather and suicide have found that suicide risk increases following exposure to excessive heat, solar radiation, and drought.

To date, studies have largely focused on the effects of single air pollutants or weather variables on suicide. Thus, complex mixtures, which more realistically reflect a person's daily exposure to ambient air pollution and weather, have not been examined in regards to suicide. In addition, the underlying characteristics that influence a person's vulnerability to suicide following exposure to air pollutants and weather variables are largely unknown, yet their recognition is critical for developing effective interventions.

The goals of the proposed study are to:

1) Investigate thoroughly the gaps in our current knowledge of the individual, additive, and combined effects of multiple short-term environmental exposures (i.e., ambient air pollutants and weather variables) on suicide risk.

2) Identify the demographic, clinical, and familial characteristics that increase a person's susceptibility to suicide following short-term exposure to ambient air pollution and weather.

3) Identify and characterize genetic variants that interact with short-term ambient air pollution and weather to increase suicide risk.

We are uniquely positioned at the University of Utah to carry out the proposed work. Data resources already available to our research team include molecular data from >5,500 cases (Illumina PsychArray data; whole genome sequence data is available on a subset of 665 cases). Clinical and demographic information is available from the Utah State Office of the Medical Examiner and the Utah Population Database (UPDB). The UPDB includes multi-generation genealogical records, demographic data, vital records data, information on early life conditions, and current medical information on ~11 million individuals in Utah.

We will use a nested case-control design analyzed in a multi-exposure Bayesian framework to quantify the effects of multiple environmental exposures and identify underlying individual-level and familial susceptibilities. Gene-environment interactions will be investigated using case-only and case-crossover study designs.

Study results may lead to the development of clinical, educational, and/or pharmacological interventions for suicide, targeted at high-risk individuals.

University Of Utah

TO FOSTER UNDERSTANDING OF HUMAN HEALTH EFFECTS OF EXPOSURE TO ENVIRONMENTAL AGENTS IN THE HOPE THAT THESE STUDIES WILL LEAD TO: THE IDENTIFICATION OF AGENTS THAT POSE A HAZARD AND THREAT OF DISEASE, DISORDERS AND DEFECTS IN HUMANS, THE DEVELOPMENT OF EFFECTIVE PUBLIC HEALTH OR DISEASE PREVENTION STRATEGIES, THE OVERALL IMPROVEMENT OF HUMAN HEALTH EFFECTS DUE TO ENVIRONMENTAL AGENTS, THE DEVELOPMENT OF PRODUCTS AND TECHNOLOGIES DESIGNED TO BETTER STUDY OR AMELIORATE THE EFFECTS OF ENVIRONMENTAL AGENTS, AND THE SUCCESSFUL TRAINING OF RESEARCH SCIENTISTS IN ALL AREAS OF ENVIRONMENTAL HEALTH RESEARCH. SUPPORTED GRANT PROGRAMS FOCUS ON THE FOLLOWING AREAS: (1) UNDERSTANDING BIOLOGICAL RESPONSES TO ENVIRONMENTAL AGENTS BY DETERMINING HOW CHEMICAL AND PHYSICAL AGENTS CAUSE PATHOLOGICAL CHANGES IN MOLECULES, CELLS, TISSUES, AND ORGANS, AND BECOME MANIFESTED AS RESPIRATORY DISEASE, NEUROLOGICAL, BEHAVIORAL AND DEVELOPMENTAL ABNORMALITIES, CANCER, AND OTHER DISORDERS, (2) DETERMINING THE MECHANISMS OF TOXICITY OF UBIQUITOUS AGENTS LIKE METALS, NATURAL AND SYNTHETIC CHEMICALS, PESTICIDES, AND MATERIALS SUCH AS NANOPARTICLES, AND NATURAL TOXIC SUBSTANCES, AND THEIR EFFECTS OF ON VARIOUS HUMAN ORGAN SYSTEMS, ON METABOLISM, ON THE ENDOCRINE AND IMMUNE SYSTEMS, AND ON OTHER BIOLOGICAL FUNCTIONS, (3) DEVELOPING AND INTEGRATING SCIENTIFIC KNOWLEDGE ABOUT POTENTIALLY TOXIC AND HAZARDOUS CHEMICALS BY CONCENTRATING ON TOXICOLOGICAL RESEARCH, TESTING, TEST DEVELOPMENT, VALIDATION AND RISK ESTIMATION, (4) IDENTIFYING INTERACTIONS BETWEEN ENVIRONMENTAL STRESSORS AND GENETIC SUSCEPTIBILITY AND UNDERSTANDING BIOLOGIC MECHANISMS UNDERLYING THESE INTERACTIONS, INCLUDING THE STUDY OF ENVIRONMENTAL INFLUENCES ON EPIGENOMICS AND TRANSCRIPTIONAL REGULATION, (5) CONDUCTING ENVIRONMENTAL PUBLIC HEALTH RESEARCH, INCLUDING IN AREAS OF ENVIRONMENTAL JUSTICE AND HEALTH DISPARITIES, THAT REQUIRES COMMUNITIES AS ACTIVE PARTICIPANTS IN ALL STAGES OF RESEARCH, DISSEMINATION, AND EVALUATION TO ADVANCE BOTH THE SCIENCE AND THE DEVELOPMENT OF PRACTICAL MATERIALS FOR USE IN COMMUNITIES, WITH A FOCUS ON TRANSLATING RESEARCH FINDINGS INTO TOOLS, MATERIALS, AND RESOURCES THAT CAN BE USED TO PREVENT, REDUCE, OR ELIMINATE ADVERSE HEALTH OUTCOMES CAUSED BY ENVIRONMENTAL EXPOSURES, (6) EXPANDING AND IMPROVING THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (7) EXPANDING AND IMPROVING THE STTR PROGRAM TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (8) PROVIDING SUPPORT FOR BROADLY BASED MULTI-DISCIPLINARY RESEARCH AND TRAINING PROGRAMS IN ENVIRONMENTAL HEALTH .THESE PROGRAMS INCLUDE THE ENVIRONMENTAL HEALTH SCIENCES CORE CENTERS , WHICH SERVE AS NATIONAL FOCAL POINTS AND RESOURCES FOR RESEARCH AND MANPOWER DEVELOPMENT. THROUGH THESE PROGRAMS, NIEHS EXPECTS TO ACHIEVE THE LONG-RANGE GOAL OF DEVELOPING NEW CLINICAL AND PUBLIC HEALTH APPLICATIONS TO IMPROVE DISEASE PREVENTION, DIAGNOSIS, AND THERAPY. ADDITIONAL CENTERS PROGRAMS DEVELOPED IN RECENT YEARS, INCLUDE THE CENTERS FOR OCEANS AND HUMAN HEALTH (CO-FUNDED WITH NSF), CHILDREN'S ENVIRONMENTAL HEALTH CENTERS (CO-FUNDED WITH US EPA) AND THE AUTISM CENTERS OF EXCELLENCE (CO-FUNDED WITH OTHER NIH INSTITUTES), AND THE HUMAN HEALTH EXPOSURE ANALYSIS RESOURCE (HHEAR) PROGRAM, (9) SUPPORTING RESEARCH TRAINING PROGRAMS WHICH SERVE TO INCREASE THE POOL OF TRAINED RESEARCH MANPOWER WITH NEEDED EXPERTISE IN THE ENVIRONMENTAL HEALTH SCIENCES THROUGH SUPPORT OF INDIVIDUAL AND INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS), (10) THE OUTSTANDING NEW ENVIRONMENTAL SCIENTIST PROGRAM WHICH PROVIDES FIRST TIME RESEARCH GRANT FUNDING TO OUTSTANDING JUNIOR SCIENTISTS IN THE FORMATIVE STAGES OF THEIR CAREER WHO ARE PROPOSING TO MAKE A LONG TERM COMMITMENT TO ENVIRONMENTAL HEALTH SCIENCES RESEARCH AND TO ADDRESS THE ADVERSE EFFECTS ON ENVIRONMENTAL EXPOSURES ON HUMAN BIOLOGY, HUMAN PATHOPHYSIOLOGY AND HUMAN DISEASE.

93.113 - Environmental Health

National Institute of Environmental Health Sciences (NIEHS) [HHS - NIH]

Salt Lake City, Utah 841081222 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 365% from $673,022 to $3,126,403.