To understand how it all begins, we look at the early markers of future ADHD during pregnancy (we look at molecules in the mother’s blood, in the cord blood, in the placenta) and in early life (we look at biology, brain, and behavior in the infant and toddler). Here our primary hypothesis is that the many different causal influences converge on a small number of biological processes that we can learn to modify. Inflammation (exaggerated immune response) is our leading and most likely candidate. We have proven it affects early brain development and behavior.

Maternal-infant origins project. This project tracks biology and social context for families from the first or second trimester of conception on into the preschool years. We use blood biomarkers from the mom, the placenta, and the cord blood and behavioral markers in the infant to understand the development of self-control, attention, and emotion regulation and to predict future ADHD and other conditions. (Elinor Sullivan, Ph.D., Jennifer M. Loftis Ph.D., Hanna Gustafsson, Ph.D., Joel Nigg, Ph.D., Alice Graham, Ph.D.)

Genetics projects. We conduct genome wide tests to identify genetic algorithms that can predict clinical profile or clinical course, and to identify which features are related to genetic cause and which may be related to other causes. (Michael Mooney, Ph.D., Stephen Faraone, Ph.D.)

To find out, we test new treatments to prevent or cure. Here we are undertaking novel clinical trials that give hope of more dramatic change for individuals. We are not limited to new drugs—we believe some cures will involve intensive nutrition or simple anti-inflammatory treatments that are better targeted. We are particularly interested in modifiable environments. As we learn more about how mental control and mental effort work in the brain in ADHD, we can also develop new kinds of computerized training tools and more effective biofeedback tools. (Sarah Karalunas, Ph.D., Joel Nigg, Ph.D., Michael Mooney, Ph.D.)

Epigenetics project. This is a novel exploration to search for chemical signals in the genome that may map on to early environmental influences and enable us to identify causes as well as biomarkers of illness and course. It involves advanced analysis of blood, saliva, and placenta samples. (Michael Mooney, Ph.D., Jonathan Mill, Ph.D., Joel Nigg, Ph.D.)

Identical twin study. When identical twins develop different clinical profiles, we know the cause is very likely to be either a rare genetic mutation or else a modifiable environment, involving epigenetic change. We have a small cohort of identical twins and examine gene expression, epigenetics, genetic sequencing, and MRI brain imaging searching for clues. (Joel Nigg, Ph.D., Michael Mooney, Ph.D., Maximilian Muenke, M.D.)

Novel clinical trials. We already have enough information to undertake some novel clinical trials. For example, in collaboration with two other universities, We are conducting the first test in the nation to determine whether intensive high dose nutrient supplementation can help children with ADHD. We also are planning other trials. (Jeni Johnstone, Ph.D., Alice Graham, Ph.D.)

We have published over 150 papers, many of them well cited, on many aspects of ADHD and its underlying nature. Here is a sampler.

• Accurately predict which individuals with apparent ADHD are on a path to bad outcome and which ones are benign—thus markedly improve clinical identification.
• Identify and verify clinical subtypes that set the state for personalized medicine. Link these to brain signals using EEG and MRI.
• Identify inflammatory biomarkers as a “common pathway” for environmental risks in early life that disrupt brain development and lead to ADHD.
• Verify biotypes in the brain—different brain scan profiles that create an ADHD “look-alike” but may need different solutions. 
• Predict ADHD risk from birth or shortly after birth so set the stage for early prevention trials in susceptible children.  
• Complete clinical trials of a novel multi-nutrient treatment for irritable mood and inattention and begin to understand mechanisms so it can be steadily improved.
• Characterize different developmental paths of ADHD in relation to changes in the brain.
• Find biological evidence of environmental cause (that is, an epigenetic algorithm that predicts back to early exposure that triggered ADHD)

• NIH:  The National Institutes of Health. US federal funding is the largest source of scientific funding in the world directed at solving mental illness and the primary source of support for mental health research for us and the U.S. community.
• Food additives means dyes, preservatives, and any synthetic chemical added to food during processing.
• Inflammation/inflammatory/anti-inflammatory refers to the biology of the immune system, involving molecules such as cytokines and others that communicate throughout the body and the brain. Intended to help the body overcome health challenges, when overactive can damage brain and behavior.
• Emotional dysregulation means people who have temper tantrums, over-react, and are extremely reactive, cannot cope with minor stress, and as a result have major problems functioning. “Irritability” is a type of emotional problem that means problems controlling anger, but associated with underlying depression.
• Brain network refers to the way different parts of the brain are functionally organized into groups, analogous to the way social groups or teams are organized. Some networks in the brain handle memory, some attention, and some emotion. We map these using physical brain imaging.
• MRI: Magnetic Resonance Imaging. A method of brain imaging that uses a strong magnetic field to change the spin direction of molecules in the brain. This is used to infer blood flow (an index of neural activity) and water flow (an index of physical fiber connections) in the brain. A good method to map brain networks.
• EEG: Electroencephalograph. A method of measuring brain electrical activity using electrodes on the scalp, it allows us to measure second by second changes in brain reaction to something, even outside of mental awareness. A good method to measure the overall degree of functionality of the brain, especially the cortex, or higher brain levels that handle thinking and regulate emotion.
• Advanced analytics: This term and terms like it—machine learning, advanced mathematics, artificial intelligence, computational models—refer to very complex (“nonlinear”) models that identify patterns in the data not available through routine analysis. Similar to methods used by google or Facebook to identify patterns in their database.
• Epigenetic refers to chemical marks on the DNA that control gene expression and can be changed by either other genes or by experiences.