On the Shoulders of Giants Science Symposium
Nora Volkow, MD, presented at the Child Mind Institute’s 2013 On the Shoulders of Giants Scientific Symposium.
The 2013 On the Shoulders of Giants Scientific Symposium honoring Nora Volkow, MD, took place on October 2, 2013, at The Roosevelt House at Hunter College.
The Role of Dopamine D2-Receptor Signaling in the Addicted Human Brain
Nora Volkow, MD
Addiction is a disorder that involves complex interactions between genes, development and the social environment. Studies employing neuroimaging technology paired with behavioral measurements and, more recently, genetics, have led to remarkable progress in elucidating neurochemical and functional changes that occur in the brains of addicted subjects. Although large and rapid increases in dopamine have been linked with the rewarding properties of drugs, the addicted state, in striking contrast, is marked by significant decreases in brain dopamine D2 receptor mediated signaling. Such decreases are associated with dysfunction of prefrontal regions including orbitofrontal cortex, cingulate gyrus and dorsolateral prefrontal cortex, and impaired striato frontal connectivity. In addiction, disturbances in salience attribution result in enhanced value given to drugs and drug-related stimuli at the expense of other reinforces and promote inflexible behaviors. Dysfunction in inhibitory control systems, by decreasing the addict’s ability to refrain from seeking and consuming drugs, ultimately results in the compulsive drug intake that characterizes the disease. Discovery of such disruptions in the fine balance that normally exists between brain circuits underling reward, motivation, memory and self-control have important implications for designing multi-pronged interventions for the prevention and treatment of addictive disorders.
Common Brain Mechanisms in Addiction and Obesity
Gene-Jack Wang, MD
Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of, others. Both drugs and food have powerful reinforcing effects — partly mediated by dopamine increases in the limbic system — that, under certain circumstances or in vulnerable individuals, could overwhelm the brain’s homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories of addiction and obesity. Our imaging findings, predominantly derived from positron emission tomography, uncover common features of these two disorders and delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, impulse control, stress reactivity and interoceptive awareness.
Brain Mechanisms at the Interface of Appetitive Drive and Energy Regulation: Implications for Psychiatric Disease
Michael Michaelides, MD
Obesity is a complex disease state characterized by deficits in appetitive drive and metabolism. Similar deficits are observed in substance abusers. Among several neurobiological systems, dopamine and the striatal dopamine D2 receptor (D2R) are heavily implicated in substance abuse, and in 2001, Drs. Wang and Volkow reported that obese and normal-weight humans differed in striatal D2R. This finding was instrumental in substantiating the notion of neurobiological similarities between obesity and substance abuse disorders. My talk will expand on this initial finding by presenting molecular, behavioral and circuit-level evidence gained from recently developed preclinical imaging and gene technologies implicating striatal D2R in the direct regulation of appetitive drive and metabolism.
About the Participants
Nora Volkow, MD, is the director of the National Institute on Drug Abuse. Dr. Volkow’s work has been instrumental in demonstrating that drug addiction is a disease of the human brain. As a research psychiatrist and scientist, Dr. Volkow pioneered the use of brain imaging to investigate the toxic effects and addictive properties of abusable drugs. Her studies have documented changes in the dopamine system affecting, among others, the functions of frontal brain regions involved with motivation, drive and pleasure in addiction. She has also made important contributions to the neurobiology of obesity, ADHD and aging.
Dr. Volkow was born in Mexico, attended the Modern American School, and earned her medical degree from the National University of Mexico in Mexico City, where she received the Robins Award for best medical student of her generation. Her psychiatric residency was at New York University, where she earned the Laughlin Fellowship Award as one of the 10 Outstanding Psychiatric Residents in the USA.
Dr. Volkow spent most of her professional career at the Department of Energy’s Brookhaven National Laboratory (BNL) in Upton, New York, where she held several leadership positions including director of Nuclear Medicine, chairman of the Medical Department and associate director for Life Sciences.
Dr. Volkow has published more than 530 peer-reviewed articles and has written more than 80 book chapters and non-peer-reviewed manuscripts. She has also edited three books on neuroimaging for mental and addictive disorders.
During her professional career, Dr. Volkow has been the recipient of multiple awards, including her selection for membership in the Institute of Medicine in the National Academy of Sciences and the International Prize from the French Institute of Health and Medical Research for her pioneering work in brain imaging and addiction science. She was recently named one of TIME magazine’s “Top 100 People Who Shape Our World” and was included as one of the 20 people to watch by Newsweek magazine in its “Who’s Next in 2007?” feature. She was also included in Washingtonian magazine’s 2009 list of the “100 Most Powerful Women” and named “Innovator of the Year” by U.S. News & World Report in 2000.
Michael Michaelides, PhD, completed his undergraduate studies in economics and mathematics at Stony Brook University in 2004. He then received an NIH Postbac Intramural Research Training Award, spending two years studying behavioral neuropharmacology and neuroimaging applications in drug abuse and addiction research in Dr. Nora Volkow’s NIAAA Laboratory for Neuroimaging. Upon completion of this training, he was admitted to the Integrative Neuroscience Doctoral Program at Stony Brook University. The vast majority of Dr. Michaelides’ doctoral work was performed at Brookhaven National Laboratory where he studied neural mechanisms implicated in addiction and obesity under the direction of Drs. John K. Robinson and Peter Thanos. During this time he also worked on the development of novel behavioral PET imaging methodologies in small animals. After receiving his PhD in 2010, he was admitted to the Postdoctoral Training Program in Drug Abuse at the Icahn School of Medicine at Mount Sinai, where he has been co-advised by Drs. Gene-Jack Wang and Yasmin Hurd. During this time, he has had the chance to extend his research knowledge to humans and has also received extensive training in molecular biology and epigenetics of drug abuse. Currently, Dr. Michaelides is a 4th year postdoctoral fellow at Mount Sinai, where he is combining his unique training in behavioral pharmacology and neuroimaging with cutting-edge molecular biology and epigenetic techniques to study the molecular and developmental basis of appetitive drive and mood and motivational disorders.
Gene-Jack Wang, MD, is a board certified nuclear medicine physician with a joint appointment as both a professor of radiology at Stony Brook University and a senior scientist at the Brookhaven National Laboratory (BNL). His research focuses on the application of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to the study of various brain disorders. He is interested in using PET to study the neuro-psychiatric mechanisms and manifestations of alcoholism, drug addiction, obesity and eating disorders in humans and in animal models. Using PET, he reported similarity of brain circuits’ disruption in drug addiction and obesity. Currently, he uses PET to study the relationship between peripheral metabolic signals and brain neurotransmitters and uses fMRI to study effect of diet control drugs on brain satiety circuit and to assess cognitive function in obese subjects. He has published over 250 peer-reviewed original papers and 50 review articles/book chapters on his imaging research. He has received the distinguished Asian American professional award from Suffolk County, New York, and the Science and Technology award from BNL.