Attention-deficit/hyperactivity disorder (ADHD)

2011 Scientific Innovations Award
F. Xavier Castellanos, M.D.
Neidich Professor of Child and Adolescent Psychiatry at
NYU Langone Medical Center and Nathan Kline Institute

Dr. Castellanos is elucidating the neuroscience of ADHD and its relationship to substance abuse through genetic studies and sophisticated brain imaging.

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition that, until recently, has defied scientific understanding. Scientific research of a disease aims to identify causes or connect symptoms to underlying physiology. Such methods are traditionally less effective for understanding a syndrome, such as ADHD, which is characterized by multiple symptoms that frequently occur together.

Recent progress in the fields of neuroimaging and genetics make it possible for scientists to answer fundamental questions that will lead to better diagnosis, treatment and prevention of ADHD. After a dozen years and an international effort, researchers have identified a gene, Latrophilin-3 (LPHN3), related to the tendency to manifest ADHD. LPHN3 is thought to be linked to a particular type of ADHD that is associated with a high likelihood of developing conduct disorder, nicotine addiction, and substance abuse disorders (SUD) including alcoholism.

The Brain Research Foundation awarded F. Xavier Castellanos a $150,000 grant to launch a project that will lay the foundation for long-term research into ADHD. Dr. Castellanos, a physician and researcher with NYU and the Nathan Kline Institute for Psychiatric Research, has designed a research project using functional magnetic resonance imaging (fMRI) to study people who carry the risk gene for ADHD and are also prone to substance abuse. The study will involve only individuals who carry informative variations of the risk gene for ADHD and who have been diagnosed with ADHD. It will compare fMRI scans of substance abusers and non substance abusers. Analyses of brain imaging data will focus on areas of the brain implicated in ADHD and in which the risk gene for ADHD is strongly expressed.

Since the grant was awarded, scientists have learned more about this specific gene and its relationship with ADHD. Specifically, they have identified variations in the gene that appear to predict even more strongly which people diagnosed with ADHD will also have substance abuse. Castellanos and his colleagues will genetically characterize participants into four relevant subgroups. One group will include substance abusers with a high-risk type of ADHD gene; substance abusers with a low-risk type; and two separate groups of non substance abusers, one high-risk and one low-risk. These individuals will undergo fMRI to yield data that will identify commonalities, as well as differences, among the subgroups.

Identification of a gene is only an initial step. Identifying which specific variations in a gene are responsible for differences in biological function can be like finding a needle in a haystack. But learning how this gene functions and malfunctions in some types of ADHD will likely reveal much about ADHD overall.

Other Awards

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Dr. Shepherd’s lab discovered that a brain gene critical for memory and cognition, Arc, has biochemical properties like retroviruses such as HIV. Arc protein can form virus-like protein capsids that…
Yuki Oka, Ph.D., California Institute of Technology
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Angelique Bordey, Ph.D., Yale University
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