Discovery Winter 2009

University Center TRIAD— Susan Gray From Dinner 4 for Excellence— 5 STAT Test Kit 8 School— 10 to Discovery Behavior Analysis Available All That a Clinic Playground Can Do Obesity, Diabetes, Transition in VKC Leadership and Brain Function By Craig Boerner and Jan Rosemergy Transition in VKC Leadership By Jan Rosemergy Vanderbilt Kennedy Center Director Pat Levitt, Ph.D., stepped down after 6 years to pursue other ne of the most significant opportunities, effective November 1. Associate O health risks shared by Director Elisabeth Dykens, Ph.D., is serving as VKC children and adults with interim director while a nationwide search is developmental disabilities conducted for Levitt’s successor. and by the general U.S. Levitt, the Annette Schaffer Eskind Chair, has population is obesity. accepted a position at the University of Southern According to the national California as Director of the Zilkha Neurogenetic Centers for Disease Control Institute and Chair of the Department of Cell and GERLINDE PHOTOGRAPHY, MICHAEL HOPKINS Pat Levitt, Ph.D. and Prevention (CDC), Neurobiology at the Keck School of Medicine and roughly two-thirds of U.S. ©LES SCHOLZ. IMAGE FROM BIGSTOCKPHOTO.COM Provost Professor of Neuroscience, Psychiatry, and Pharmacy. adults aged 20 and over are The Vanderbilt Kennedy Center (VKC) has expanded greatly under Levitt’s overweight or obese, and the prevalence has increased sharply for both adults direction, more than doubling its extramural research portfolio, experiencing a and children since the mid-1970s. Obesity rates remain high, at 31.9%, among fortyfold increase in philanthropy, being designated a University Center for children and adolescents ages 2-19 years. Excellence in Developmental Disabilities, and assuming oversight of the Little is known about the national or state prevalence of obesity among LEND/MIND Training Program. Autism research and treatment programs also persons with disabilities, because it is not routinely measured or reported. One have seen dramatic growth through the Treatment and Research Institute for study (Rubin et al., 1998) found that in a sample of 290 persons with Down Autism Spectrum Disorders (TRIAD), the Marino Autism Research Institute, syndrome, 45% of men and 56% of women were overweight using the criteria and related activities. established in the Healthy People 2000 report, a finding that suggests that the “In my view, many of the programs now require leadership in clinical prevalence of obesity is likely to be even higher in persons with developmental research, clinical and translational services, and training areas, which are not my disabilities than in the general population. strengths,” said Levitt, a professor of pharmacology. “I know that the Center will benefit from fresh leadership. The Obesity and Type 2 Diabetes administration has been very Obesity increases the risk for many diseases, including type 2 diabetes, supportive, and I am not stepping hypertension, cardiovascular disease, respiratory problems, certain cancers, and down because of any problems.” lowered life expectancy. Among obesity-related diseases, national attention is “Pat has provided extraordinary being devoted to the increase in type 2 diabetes. According to the CDC, from leadership,” said Dykens, also co- 1980 through 2005, the number of adults aged 18-79 with newly diagnosed director of the VKC University Center diabetes almost tripled from 493,000 in 1980 to 1.4 million in 2005 in the U.S. for Excellence in Developmental “Obesity and diabetes not only are major health problems in and of Disabilities. “He gave priority to family themselves,” said Kevin Niswender, M.D., Ph.D., “but they also have and community needs. Pat and his implications for mental health, depression, attention deficit hyperactivity disorder (ADHD), and even substance abuse.” colleague BethAnn McLaughlin built a Niswender, assistant professor of medicine and molecular physiology & relationship with the Dan Marino biophysics, is a physician-scientist who conducts innovative research on diabetes KYLIE BECK Foundation, which is now supporting the Marino Autism Research Institute and obesity. He has teamed with Vanderbilt Kennedy Center investigator Elisabeth Dykens, Ph.D. Aurelio Galli, Ph.D., associate professor of molecular physiology & biophysics, at Vanderbilt and the University of who studies the mechanisms for how neurotransmitter imbalance leads to Miami. Working with deans and department chairs, he helped recruit 20 new neurological disorders such as schizophrenia, ADHD, and addiction to scientists to Vanderbilt. Pat also built relationships with donors that have led to substances of abuse. important programs for families like the Ann and Monroe Carell Jr. Families “What Dr. Galli and other cutting-edge investigators have hit on is that First Workshops for parents of young children with autism. In short, Pat has addiction biology is involved to some degree in human Continued on page 2 been an awesome leader.” Continued on page 3 Number 23 Winter 2009 Vanderbilt University Winter 2009 Discovery clinical relevance such as Ritalin (used for treatment “but in humans, where food intake usually occurs in Obesity, Diabetes from page 1 of ADHD), act upon these transporters to alter the a discrete meal, there are many nonhomeostatic concentration of dopamine in the synaptic cleft. mechanisms as well. Eating foods that are high in fat feeding behavior and potentially in the obesity and “The focus of my laboratory,” Galli said, “is to try and simple carbohydrates tickle the same parts of diabetes epidemics,” Niswender said. “What is really to understand the mechanisms of action of these the brain that substances of abuse activate and that phenomenal is that his work brings the process full drugs with the intent to improve the mediate addiction. The work of Dr. Galli and others circle. The brain controls appetite, shows that dopamine is one of the feeding, and ultimately insulin key neurotransmitters involved in production. What we’re beginning addiction and now, we think, in to understand is what happens feeding biology as well.” downstream; insulin itself actually Insulin’s role typically is feeds back to the brain and regulates associated with blood sugar control many of the processes involved in and diabetes. “The whole idea that feeding and potentially addiction, insulin does anything in the brain cognition, and other aspects of is beginning to receive increasing neurological function that were attention,” Niswender said. previously not thought to be The brain requires glucose, and ‘metabolically’ regulated.” the body requires insulin in order to use glucose effectively, he Brain Dopamine and Obesity explained, but the brain does not Food intake is regulated by several require insulin for glucose neurotransmitters, including metabolism. In fact, insulin in the dopamine, GABA, norepinephrine, brain reflects what the energy stores © CELSO PUPO. IMAGE FROM BIGSTOCKPHOTO.COM and serotonin, as well as by peptides in the body are, so that the brain and amino acids. Dopamine is of special interest pharmacological treatment of specific neurological can generate adaptive responses. If one fasts and the because it seems to regulate food intake by disorders and substance abuse—and now perhaps glucose level drops, insulin levels drop, and that modulating the “reward” circuitry of the brain. also obesity and type 2 diabetes.” reduction in insulin levels signals, in a homeostatic Drugs that block certain dopamine receptors This latter goal is the result of a major finding by way, that one needs to eat. increase appetite and lead to significant weight gain, the Galli laboratory that insulin itself is a potent “We think now that when one overeats, insulin while drugs that increase brain dopamine levels regulator of DAT function. By controlling DAT has a different function,” Niswender said. “Insulin dampen appetite and lead to weight loss. The function, insulin fine-tunes dopamine levels in the acts on those areas of the brain where dopamine involvement of dopamine in pathological eating and brain and therefore reward. Most recently, Galli’s normally functions to decrease the reward aspect obesity is not yet well understood, but it is an area of research has moved to focus more broadly on reward of food intake, thereby helping to limit food intense interest. processes in the brain. intake. It is likely that this novel function of Galli indicated that they insulin is compromised in obese people. It is are discovering that when intriguing to think that when people eat a high- an animal starts to become fat, high-carbohydrate diet, their food intake stays obese, the dopaminergic elevated, because insulin resistance causes the function that is involved in dopamine system to no longer be able to be the reward process, as well turned off and to compensate for the caloric as in cognition and motor intake and increased reward.” activities, is altered. The Galli’s lab has identified the molecular pathway dopamine transporter from the insulin receptor all the way through to the leaves the plasma dopamine transporters in the brain, which membrane, affecting both Niswender characterized as “phenomenally novel dopamine clearance and and important.” brain dopamine levels. The Galli pointed out that diabetes has co-morbidity group hypothesizes that with other disorders, including ADHD, motor because of brain insulin impairment, depression, and aggression. The resistance that develops in underlying biological mechanisms of these disorders KYLIE BECK

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