What is “NICHES”?  The Center for Study of Neurodevelopment and Improving Children’s Health following Environmental tobacco Smoke exposure (NICHES) is a new Children’s Environmental Health and Disease Prevention Research Center. NICHES is funded by grants from the National Institute of Environmental Health Sciences and the United States Environmental Protection Agency. The NICHES Children’s Center will investigate how secondhand smoke (SHS) exposure during early life increases the risk of developing attention-deficit / hyperactivity disorder (ADHD).

Why is tobacco smoke exposure a problem? Nearly half of the world’s children are exposed to SS, a major environmental risk factor for ADHD, which is the most common psychiatric disorder in childhood. The Centers for Disease Control and Prevention (CDC) report that over 5 million US children ages 4-17 have been diagnosed with ADHD, a number increasing 5.5% each year. Genetic factors explains about 75% of ADHD, but the remaining 25% is related to the environment, likely through changes in the way the cells function.  We believe these changes are brought about through environmental exposures like cigarette smoke, or second hand smoke, that disrupts the way the genes in our DNA are regulated, making some of them too active, and others too inactive.

What is NICHES going to do?  Our long-term objectives are: (1) to identify tangible mechanisms to improve therapeutic options for treatment of ADHD, and (2) ultimately to identify the means to reduce ADHD burden through preventative or ameliorative strategies. We expect achieving these objectives to require development of epigenetic biomarkers to identify at-risk children based on an epigenetic archive of past SHS exposure, making possible earlier use of novel ameliorative treatments. We hypothesize that epigenetic alterations induced by SHS exposure in early life are mechanistically responsible for altering neurodevelopment and neuronal function, which manifest as altered neurobehaviors associated with ADHD. Our hypothesis is based on our own preliminary data, as well as on emerging reports showing DNA methylation changes, including those detectable in blood, are involved in the etiology of neurologic dysfunction in psychiatric disorders. Our rationale is that the proposed research will identify specific molecular targets and how they are deregulated, information that can be used to develop screening tools and targets for developing novel treatments. We have four overall specific aims:

Aim 1: To define relevant epigenomic-transcriptomic changes induced by nicotine exposure. We will use an in vivo rat model of ADHD (Project 2) to define related epigenomic-transcriptomic changes induced by nicotine exposure in brain and blood (Project 3), and extend these results through our pre-existing longitudinal human cohort of mother-infant pairs to quantitatively test the relationship between SHS and DNA methylation (Projects 1 and 3).
Aim 2: Examine the effect of exposure timing on outcome and epigenetic effects. We will test prenatal vs. postnatal exposure on behavioral phenotypes in rodents (Project 2) and humans (Project 1). Mechanistic studies of neuronal differentiation and function in vitro (Project 2) will be related to changes in DNA methylation (Project 3) in mediating observed phenotypes or disordered neurodifferentiation, and potential remediating effects of one-carbon pathway donors and antioxidants will be explored (Project 2).
Aim 3: Determine if methylation mediates the relationship between SHS exposure and ADHD-related neurobehaviors. We will define mediating effect of DNA methylation (Project 3) on the relationship between SHS exposure and neurobehavioral phenotypes in humans (Project 1) and rodents (Project 2).

Aim 4: Train multidisciplinary researchers to impact environmental health sciences. We will promote training and development of multidisciplinary researchers in environmental health sciences, including our Faculty Development Investigator (a computational biologist), graduate student, postdocs, and undergrads.

We believe this work will substantially improve understanding of the environment’s role in ADHD, generate potential new biomarkers, and identify new targets for developing treatments. This work will also train future scientists as well as educate the public and clinicians about the harms of environmental tobacco smoke.

NICHES is supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under award number P01ES022831 and by US EPA grant RD-83543701. The content of this web site is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or USEPA.