UC Davis M.I.N.D. Institute • Medical Investigation of Neurodevelopmental Disorders

. . . . MIND Matters WIN T E R 2 0 0 8

Exploring links among , the immune system and the

What causes autism, a neurodevelopmental disorder that now affects 1 in 150 children in the United States? Although studies suggest a strong genetic basis, scientists are also looking into possible biological and environmental origins, and among the most fascinating areas under investigation is the link between the immune and nervous systems. Researchers are exploring whether changes within the developing immune system could compromise nervous system development and ultimately lead to such disorders as autism. UC Davis researchers are at the leading edge of this field of inquiry, spurred on in large part by the synergy created when the M.I.N.D. Institute began supporting scientists from varying backgrounds to work on related problems. For instance, Kimberley McAllister, and Judy Van de Water, basic scientists at UC Davis’ Center for and Center for Neuroscience associate professor Kimberley McAllister is M.I.N.D. Institute respectively, are working on complementary investigating whether environmental factors can trigger changes in aspects of the immune system-autism question. Their M.I.N.D. immune system molecules like MHCI to contribute to autism. Institute-funded studies are creating a unique set of parallel building blocks that could well lead one day to a definitive quently altered by experience. She believes that environmentally explanation of a potential contributor to autism. triggered changes in certain immune system molecules within “The synergy between the outstanding basic science the developing brain could interact with genetic factors to cause research at the Center for Neuroscience and the translational several neurodevelopmental disorders, including autism. focus of the M.I.N.D. Institute helps basic scientists like me to She and her team have recently received grants from Autism design their experiments in a way that maximizes the potential Speaks, a nonprofit funding biomedical autism research, and the for understanding disease,” M.I.N.D. Institute to test this idea. The rationale behind Inside explains McAllister, an associ- this theory is: ate professor who began her • MHCI (short for ”major histocompatibility complex I”) Animal models help unravel academic studies as a medical molecules mediate the adaptive immune response. autism mysteries...... 3 student before getting hooked • MHCI molecules are present in nerve cells, or neurons. • It’s possible that changes in MHCI in developing brain Working on the “ultimate on basic science and switching machine” drives a career... 6 tracks, ultimately earning a neurons contribute to autism by altering the way that doctorate in neurobiology from synapses develop. Neuroscientist studies • Those changes in MHCI are typically triggered by environ- consciousness and brain Duke University in 1996. functions...... 7 mental factors or an immune response. A focus on MHCIs • Environmental factors (such as an immune response) may Disc jockeys team up to raise McAllister’s laboratory stud- alter synaptic connectivity in the developing brain. autism awareness...... 10 ies how synapses, the points • Rather than impact MHCI directly, environmental factors Executive director’s at which impulses pass from affect MHCI through cytokines, proteins that regulate message...... 12 one nerve cell to another, are intercellular communication within the immune system. initially formed and are subse- (continued page 2)

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Exploring links (from page 1)

• Several cytokines have been found to indicates problems in proper signaling of be up-regulated, or overly active, in cells to produce certain proteins or factors, “The science of brain the of children with autism. potentially rendering these children more development is remarkable. • Perhaps these cytokines alter syn- susceptible to infections. aptic connectivity in the developing “Indeed, this tells us that there is likely It’s amazing how brain by altering MHCI levels, and something wrong in communication environment and experience those alterations in turn contribute among cells within the developing immune to autism. systems of these children,” says Van de physically change the “This is an exciting but as yet Water, who is also a professor in rheuma- connectivity of the brain.” untested hypothesis,” she explains, “If tology, allergy and clinical immunology. “It it proves true, then understanding how may be a very basic cell-signaling pathway – Kimberley McAllister, Ph.D. MHCI molecules and cytokines act problem – that is, cells are not being sig- in the developing brain could, in the naled correctly to produce needed amounts future, reveal possible therapeutic tar- of IgG.” Her studies found that antiviral gets for preventing or treating autism.” Her further work has led to the identi- responses are fairly normal in people McAllister, who received the Young fication of IgG antibodies to human brain with autism – but antibody responses to Investigator Award in 2006 from the proteins as a potential marker of autism, vaccines against bacteria were lower than Society for Neuroscience for her highly an important development in light of the expected. This suggests that the problem regarded work, points out that we are dearth of biological diagnostic tools or may lie in the way that invading pathogens far from understanding the role of therapeutic targets for this disease. In this are processed. immune molecules in normal brain case, children with autism appear to have Today, her goal is also to study what development generally, much less their very specific antibodies to proteins in the happens during gestation that may affect role in such disorders as autism. But brain, which may indicate damage to that neurodevelopment, including whether the tools are now available to make region of the brain. the mothers of children with autism have rapid progress in this area. autoantibodies to fetal brain proteins. “The science of brain develop- Vaccines and autism “Through the years we’ve learned that ment is remarkable. It’s amazing how Van de Water began her academic career many children with autism don’t have environment and experience physically pursuing a bachelor’s degree in biological healthy immune systems. We are attempt- change the connectivity of the brain,” sciences at UC Davis. An internship in ing to answer questions such as, ‘Why do she says. “Ultimately, the goal of my an immunology lab there so intrigued they have such dysfunctional systems?’ research is to try to understand just her that she decided to specialize in and ‘To what extent is the dysfunctional how that happens.” the field, eventually earning a Ph.D. in immune system linked to abnormal brain immunology in 1988. Her specialty is development?’” she says. Autism and antibodies autoimmunity, a condition in which the Developments in the field are moving Van de Water and her team are inves- immune system starts reacting against an fast. As M.I.N.D. Institute Research Direc- tigating biologic mechanisms of the individual’s own body. tor David Amaral explains, “While the immune system in relation to autism, “Until the late 1990s, researchers inves- brain was long thought to be an immu- focusing on both the blood factors tigated autism primarily from the viewpoint nologically ‘privileged’ part of the body, and cells that are involved in a healthy of behavior and genetics, not biology. Then meaning devoid of an immune system, we immune response. came MMR,” she explains, referring to a now know that the immune and nervous For example, they are currently live viral vaccine against measles, mumps systems are intimately interconnected.” analyzing an antibody subtype that’s and rubella (MMR) that was implicated as He adds, “The M.I.N.D. Institute responsible for the majority of the a cause of autism in a controversial 1998 is proud to support cross-disciplinary immune response to invading patho- study. The M.I.N.D. Institute issued a call researchers of the caliber of Drs. McAl- gens. Called immunoglobulin G, or for projects that might shed light on the lister and Van de Water as they further IgG, its levels are much lower than question. Van de Water signed up and she unravel such mysteries to advance an normal in children with autism. This has been with the institute ever since. understanding of all the .”

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Animal models crucial to unraveling autism mysteries

In fascinating studies supported by the UC Davis M.I.N.D. Institute and the National Institutes of Health, two UC Davis researchers and their teams are taking different, yet parallel, paths in the urgent task of uncovering the causes of autism. While one researcher has already learned a great deal about potential triggers of autism by exposing rhesus monkeys to autoantibodies (antibodies that attack one’s own cells), the other is now embarking on the same type of study using mice. In new studies, one uses the rhesus monkey animal model to study potential triggers of schizophrenia and Neurological surgery professor Robert Berman studies brain development and behavior in mice to the other uses mice models to look at better understand disorders like autism. potential causes of two neurodegenera- tive, gene-linked diseases, FXTAS and models to test hypotheses about the . They hope that by causes of autism and related disorders. “Both mice and monkey learning the causes of these diverse Mice, for instance, have life spans of diseases they’ll also learn more about about two years, enabling studies over the models have already helped the causes of autism, as each disease lifetime of the animal. We can study mice us make tremendous progress shares subtle similarities with autism. with specific genetic mutations, allowing us to model certain neurodevelopmental in autism research, to the Animal models disorders.” point where treatment can It’s no accident that these studies “We already know a great deal about feature animal models. As these brain development and behavior in these be considered.” researchers are quick to point out, animals and can therefore examine how – David G. Amaral, Ph.D. almost every major medical advance of development can be altered by genetic the last century is due to research with mutations, exposure to environmental animals. toxins or immune system dysfunction.” M.I.N.D. Institute Research Direc- Her team has zeroed in on immuno- tor David Amaral explains, “Animal Antibodies from mother to child globulin G, or IgG, an antibody subtype research is an important component Amaral has just completed a study that’s responsible for the majority of the of our program, helping us make building on work by M.I.N.D. Institute immune response to invading pathogens. significant progress in understanding researcher Judy Van de Water. She has About 20 percent of women who have autism’s causes and potential cures. To investigated whether the mothers of had a child with autism have abnormal move from hypotheses to clinical treat- children with autism have abnormally IgG antibodies that interact with the fetal ments, it’s essential that appropriate strong immune responses to proteins in brain, while women of typically developing animal research be carried out.” the fetal brain, and, if so, what role might children do not have these antibodies. This Adds neurological surgery professor such antibodies play in the development has raised the possibility that some autism Robert Berman, “We rely on animal of some cases of autism. (continued page 4)

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Unraveling autism mysteries (from page 3)

may be caused by the interaction of He notes that this is one of the first “The hypothesis is that the these antibodies with the developing examples in autism research where a fetal brain. study has gone from a clinically sug- mother’s immune response “We’ve tested the autoimmune gested hypothesis to actual testing of a interacts with the fetal development hypothesis by using cause of a neurodevelopmental disorder. the rhesus monkey model, injecting Exciting as this work is, Amaral is brain, leading to such pregnant monkeys with human IgG insistent that it must be replicated in a behavioral abnormalities as and observing their offspring for one larger, more comprehensive study. and one-half years,” explains Amaral, a “Obtaining funding for the follow-up schizophrenia or autism.” professor of and behavioral work has been difficult since it is not yet – David G. Amaral, Ph.D. sciences whose work has just been accepted that the immune system plays a accepted for publication in the journal role in autism – but we are hopeful that Brain, Behavior and Immunity. publication of our findings will support Other monkeys were injected with our grant applications,” he says. IgG purified from mothers of typically If the findings are confirmed, the working with rhesus monkeys to deter- developing children and some mon- logical next step will be clinical protocols mine if the same phenomenon is true in keys were left untreated. derived from these studies, such as blood primates. “This was an incredibly long-shot tests isolating IgG as a diagnostic marker In the earlier mice study, Patterson’s experiment since millions of things and developing strategies for removing team triggered an artificial immune outside of our control could have this risk factor from pregnant women. response in pregnant mice, in effect caused failure,” says Amaral. Berman, director of the UC Davis giving them a faux case of the flu. The Rhesus monkeys were chosen Neurotrauma Research Laboratory, trigger they used was a snippet of double- because, unlike other animals, there is working with M.I.N.D. Institute stranded RNA called polyI:C, which fools are no areas of the human brain that researchers Isaac Pessah and Van de the immune system into thinking that cannot also be found in this species. Water to test the same hypothesis in there has been an infection by an RNA In addition, more than any other lab mice models. They’re injecting human virus. Amaral and Patterson are currently animal, rhesus monkeys use facial IgG from mothers of children with following the same tack, having received expressions and body posture to autism into pregnant mice to see if there a grant from the Simons Foundation to convey social intentions, an important is a toxic effect on brain development replicate Patterson’s mouse studies in the characteristic for autism studies. and consequent changes in complex monkey model. As Amaral explains, “the social cognitive function in the offspring. “The hypothesis is that the mother’s repertoire of monkeys is very broad, immune response interacts with the in many ways approaching that of A link to schizophrenia fetal brain, leading to such behavioral humans, making it ideal for the analy- Amaral recently began a study in col- abnormalities as schizophrenia or autism,” sis of both normal and pathological laboration with California Institute of explains Amaral. “This research has human social behavior.” Technology colleague Paul Patterson to potential public policy implications. The The study’s findings were strik- test the theory that women who have outcome will hopefully inform public ing. Working at UC Davis’ California an immune response to a virus in the health officials concerning the wisdom of National Primate Research Center, second trimester of pregnancy are at suggesting or even mandating immuniza- Amaral’s team found behaviors in increased risk of giving birth to a child tion of women during pregnancy.” the offspring that resemble autism with symptoms of schizophrenia or spectrum disorder symptoms. Called autism. Last fall, Patterson published a A connection to FXTAS profound stereotypies, they include Journal of Neuroscience paper showing Berman is looking into the causes of two constant pacing, repeated backflips this to be true in mice, and now Amaral diseases that share symptoms with autism: and hyperactivity. and colleague Melissa Bauman will be fragile X-associated tremor/ataxia syn-

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drome (FXTAS) and Rett Syndrome, a abnormal social behavior. Other childhood neurodevelopmental disorder. symptoms include loss of use FXTAS typically affects men over age of the hands, slowed brain and 50, causing tremors, balance problems head growth, gait abnormalities, and dementia, all of which progres- seizures and mental retardation. It sively worsen over time. It’s caused by a affects females almost exclusively. change in the fragile X gene, called the “We are using a mouse model FMR1 gene, on the X chromosome. of Rett syndrome, a disorder The section of the FMR1 gene that’s associated with mutation involved in fragile X is called the pro- in another fragile X-linked gene, moter, and it contains a specific pattern MeCp2,” says Berman. Mice with of DNA (the molecule that makes up a mutation on this gene display genes) called a CGG repeat. A normal many of the symptoms of Rett FMR1 gene contains about 10 to 50 syndrome. CGG repeats; individuals who have a “In collaboration with Janine fragile X premutation have about 55 to LaSalle from the Department of 200 CGG repeats and develop FXTAS, Medical Microbiology and Immu- while those with a full mutation have nology and Isaac Pessah, we’re over 200 CGG repeats and develop the seeking to understand whether fragile X mental retardation syndrome. early exposure to such environ- Working with Paul Hagerman at mental toxins as PBDEs might contribute David Amaral, UC Davis M.I.N.D. Institute the M.I.N.D. Institute and consortium to neurodevelopmental disorders.” research director. investigator Rob Willemsen at Erasmus PBDEs, short for polybrominated University Medical Center in Rotterdam, diphenyl ethers, are found in flame retar- What we can learn Berman’s lab is funded to study mice dants used in a wide array of household Berman is optimistic about the potential with a very similar mutation on the products, including fabrics, furniture and of such studies. FMR1 gene to that found in human electronics. “Mouse models allow us to study the patients with FXTAS. The hypothesis, Berman points out, causes of neurodevelopmental disorders “Our ultimate goal is to develop new is that certain gene-environment interac- with the long-term goal of developing treatments to halt or reverse FXTAS, tions may underlie or increase the risk to new treatments. The more we learn about including pharmacological treatments humans of having neurodevelopmental autism, the better our ability to develop and gene-targeted therapies, for which disorders such as autism. new mouse models, thereby allowing us these mice are ideal,” explains Berman. “We are interested in understanding to approach questions that have been “There is now evidence that some young how exposure to such environmental difficult to study in humans, including males with the FXTAS premutation toxins as PBDEs and mercury early in autism’s causes and eventually optimal also show autism-like behaviors, so, by development may disrupt the brain and treatment strategies.” understanding this disease, we hope to possibly result in neurodevelopmental Adds Amaral, “Both mice and monkey learn more about autism as well.” disorders,” he says. models have already helped us make “By using genetically modified mice tremendous progress in autism research, A link to Rett syndrome modeling FXTAS and Rett syndrome, we to the point where treatment can be Rett syndrome is a childhood can understand the underlying cellular considered. One day we will learn enough neurodevelopmental disorder charac- mechanisms that result in these disorders about this disease to develop truly effec- terized by normal early development and test new therapies that can halt pro- tive treatment strategies, and in large part followed by such autistic-like behaviors gression. Our hope is that much of what we will have animal research to thank for as distinctive hand movements and we learn can be applied to autism as well.” getting us there.”

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Working on the “ultimate machine” drives career in neuroscience

As an undergraduate student at Rut- tively short period gers University in the 1980s, Stephen of time during C. Noctor had to take a course called development of ‘Conditioning and Learning’ to get his the cerebral cortex. bachelor’s degree. Part of the charm In particular, he was the enthusiasm of the professor, investigates the Charles F. Flaherty, an authority on factors that control learning and memory who died of proliferation of the cancer in 2004. But the subject matter, precursor cells that which included instruction in the nuts produce cortical and bolts of brain anatomy and brain neurons and glia, chemistry, was the real draw. and how cortical “It was where I first learned about cells migrate to brain cells and neurotransmitters,” reach their appro- recalls Noctor, a 43-year-old neuro- priate position. Assistant professor of psychiatry and behavioral sciences Stephen C. scientist who joined the M.I.N.D. Given their tiny Noctor specializes in the study of cell growth and migration in the Institute in July. “It completely turned size – on the order developing brain. me on.” of 5 microns – the Noctor ended up volunteering in distances these cells travel within the a disease characterized by a lack of brain Flaherty’s laboratory for two years developing brain are vast. “It’s the equiva- folding that leaves its victims severely while he completed his undergradu- lent of climbing the Empire State Building compromised, occurs when too few cells ate studies, a time during which he four times,” Noctor said. And the new- are produced. Noctor said autism may “learned how laboratory science was born cells do climb – on the scaffolding be caused by deficits in the proliferation done.” Then in graduate school, at provided by a type of neuronal precursor process. the Uniformed Services University of cell called radial glial cells that Noctor has Noctor is hopeful that the great strides the Health Sciences in Bethesda, he identified through his research. that have been made in brain research in supplemented his neuroscience train- “We used to think the newborn recent years, advances that he said are due ing with medical courses. neurons just went from point A to point to the “molecular biology revolution” and From a young age Noctor had B,” he says. “But we now know that there breakthroughs in genetics, will eventually shown signs of a scientific turn of are important staging areas where the lead to treatments for such conditions. mind. “I liked taking things apart to migrating cells stop and wait to receive “In the last 10 years, we’ve learned see how they worked,” relates Noctor, information about what to do next.” more about the brain than in the previous who grew up in New Jersey. “I started Complex signaling pathways regulate century,” Noctor says. with clocks.” this extraordinary process of cell produc- That’s not to say he and other neu- So it shouldn’t be surprising that tion and migration. And, not surprisingly, roscientists don’t have a lot left to learn. Noctor, who earned his doctorate in a number of neurological disorders result “The brain is still a black box. There are neuroscience in 1998 and then did a when things go wrong. so many questions that remain unan- five year post-doctoral stint at Colum- Sometimes cells go to the initial swered.” bia University in New York, would staging area and, for unclear reasons, fail Maybe that explains why Noctor seems become an expert in the inner work- to move further. Abnormal cell migration just as excited about neuroscience today ings of what might be thought of as the can lead to conditions like double cortex as he was when he took that undergradu- ultimate machine – the human brain. syndrome, a rare disorder which can cause ate course at Rutgers back in the 1980s. Noctor’s area of expertise has to mental retardation and epilepsy and is “Science is both my job and my hobby. do with the explosion in brain cell due to a misplaced layer of nerves that It sounds geeky, but I spend most of my production that takes place over a rela- develop under the cortex. Lissencephaly, spare time in the lab.”

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Neuroscientist studies consciousness and brain function

While Clifford Saron does not set aside a period of time each day to meditate, his commute between home in Marin County and work in Davis and Sacramento – an hour-plus each way – gives him the opportunity for, if not relaxation, at least reflection. “I’m a road yogi,” quipped the 54-year-old Saron, who specializes in using electrophysiological and behav- ioral methods to study sensory integra- tion and the training of attention skills. Among other things, he is presently directing a large study examining how intensive mental training techniques Center for Mind and Brain assistant research scientist Clifford Saron investigates responses to such as meditation can influence multimodal stimuli in children with disorders. cognitive flexibility, a variety of atten- tion-related skills, emotion regulation and biomarkers of stress. who recalled his years as a student as a data gathered from electrodes attached to A recent addition to the M.I.N.D. “heady” time. “There was beginning to the scalps of research subjects, concluded Institute, Saron has been a researcher be a sense that tools and techniques were that the two halves of the brain were with UC Davis’ Center for Mind and becoming available to investigate aspects highly interdependent for a task that most Brain since 2002. He dates his fascina- of conscious and unconscious processing researchers thought involved only one tion with the organ between our ears to in the brain.” side of the brain. his middle school years, when he first Saron would go on to use some of “I was able to show that both sides began to wonder “how mind arises those methods – many (up to 128) elec- of the brain were active before research from matter.” trodes attached to the scalp to detect brain subjects responded to a visual stimulus Aside from his father, an elec- activity, response time measurements to that initially only projected to one side of trical engineer with interests in auditory and visual stimuli – in a variety the brain,” Saron said. Noting that there consciousness, one of this New York of research efforts, including studies that are some 250 million connections in the native’s early influences was David assessed the extent to which the left and corpus callosum, the structure between McClelland, a prominent personal- right hemispheres of the brain were inte- the two hemispheres, Saron said “there’s ity and social psychologist who died grated and what might result from deficits lots of evidence that mental function is in 1998 and whose teachings Saron in such integration. not so neatly lateralized” as had once been became exposed to while an under- In a 1992 paper, Saron and Richard thought. graduate at Harvard. At Albert Einstein Davidson, a professor of psychology and At the M.I.N.D. Institute, Saron is College of Medicine, where he was a psychiatry at the University of Wisconsin taking part in the Autism Phenome Proj- graduate student, Saron found another in Madison (with whom Saron worked ect, the largest and most comprehensive mentor when he became a student of closely for 14 years) known for his work assessment of children with autism ever the neuroscientist Herbert Vaughan, on the neural substrates of emotion and attempted. It aims to distinguish among a pioneer in the field of sensory and emotional disorders, identified a subgroup recognized subgroups, or phenotypes, of cognitive electro-physiology. of dyslexic individuals who exhibited autism. It will link these different forms of “Vaughan developed methods to problems in inter-hemispheric commu- autism with distinct patterns of behavior approach estimating where in the brain nication. And in his 1999 doctoral thesis, and biological changes. signals were coming from,” said Saron, Saron, on the basis of stimulus response (continued page 8)

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Consciousness and brain function (from page 8)

Saron, along with another insti- differences in their response to different component of social interaction. Also, in tute faculty member, Susan Rivera, volumes of noise, which was not the case collaboration with Takarae and M.I.N.D. post-doctoral scholar Yukari Takarae for typical children. Institute faculty member Tony Simon, and junior specialist Rita Beransky, Saron emphasized that some of the Saron is continuing to examine communi- is investigating how individuals with data is highly preliminary – only a small cation between the hemispheres, only this autism combine information from group of children have been studied so time in children with a deletion of part of different senses such as sight, sound far. But he said “the process of multi- their 22nd chromosome, using methods and touch. sensory integration appears impaired derived from his doctoral work. What they have found so far for some children with autism spectrum As for that meditation study, dubbed is that the brains of children with disorder.” The Shamatha Project after a Tibetan autism respond to visual, auditory, In addition, Saron’s lab is also term for stable attention, Saron said and touch stimuli – such as flashing studying, in collaboration with human that early results of the project, which is lights or tones or taps to the finger development graduate student Costanza based on everything from behavioral and – in a fundamentally different way Colombi and M.I.N.D. Institute faculty brain wave data to blood samples, will be than typical children. For example, in Sally Rogers and Susan Rivera, how the presented at a conference in the spring. an electrophysiological study that is brains of individuals with autism respond Until then, he uncharacteristically, isn’t part of the Autism Phenome Project, to the perception of goal and non-goal saying much, except that “we’ve got a Ft. children with autism showed little directed movements, an important Knox’s worth of data.”

Distinguished Lecturer Series

Join us for another season of inspiration and ideas from prominent researchers and physicians who provide the latest infor- mation on the science and treatment of autism and other leading neurodevelopmental disorders.

February 13, 2008 May 21, 2008 Russell A. Barkley, Ph.D., Medical University of South Carolina Christopher J. McDougle, M.D., Indiana University 4 p.m. – Life Course Impact and Mental Health Outcomes of 4 p.m. – The Pharmacotherapy of Autism and Other Children with Attention-Deficit/Hyperactivity Disorder Pervasive Developmental Disorders 6 p.m. – Attention-Deficit/Hyperactivity Disorder: Advances in 6 p.m. – Practical Aspects of Medication Treatment in Diagnosis, Understanding, Causes, and Management Autism for Parents and Other Providers

March 12, 2008 June 11, 2008 Carolyn B. Mervis, Ph.D., University of Louisville Deborah Fein, Ph.D., University of Connecticut 4 p.m. – Language and Cognitive Development of Children 4 p.m. – Can Children with Autism ‘Recover’? with Williams Syndrome or Duplication of the 6 p.m. – Early Detection of Autism Spectrum Disorders: Williams Syndrome Region State of the Science

6 p.m. – Early Development of Children who have Williams Syndrome or Down Syndrome For more information about the lecture series offered at the M.I.N.D. Institute and to view recordings of past lectures, April 9, 2008 Laura Schreibman, Ph.D., University of California, San Diego visit our Web site: www.mindinstitute.org. 4 p.m. – Developing Individualized Treatment Protocols for The M.I.N.D. lecture series is supported with a generous Children with Autism gift from Mort and Marcy Friedman. 6 p.m. – The Science and Fiction of Autism

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Participate in research

Current research

One of the ways that all parents can help find causes, treat- ments and, eventually, cures for neurodevelopmental disorders is to enroll their children in clinical research studies.

At the M.I.N.D. Institute, dozens of studies are under way on autism, , developmental delay, Tourette syndrome, attention deficit hyperactivity disorder, 22q11.2 deletion syndrome and other neurodevelopmental disorders. Research assistant Kathy Keihl (left) and Child Life specialist Erin Roseborough These studies focus on: organized this year’s Thank-you Party, which brought together hundreds of parents n interventions and children who participate in leading edge research at the M.I.N.D. Institute. n genomics

n brain structure

Clinical study to assess children with autism n immunology

n learning patterns and more Although all who are affected by autism have some difficulties with social Children who have developmental interactions, communication skills and behavior patterns, specific symptoms and severity differ widely among individuals. This diversity is a major concerns, as well as those who do roadblock to scientific progress and to clinicians’ abilities to effectively treat not, are eligible to enroll. the disorder. For more information about The Autism Phenome Project, a longitudinal study that will collect the studies that are enrolling biomedical and behavioral data from 1,800 children and their families over participants, visit the M.I.N.D. the course of five to eight years, will address these issues. Institute Web site at www. Parents with children who are 2 to 3 1/2 years of age with either autism mindinstitute.org, or call clinical or typical development are invited to enroll their children in this longitudinal research coordinator, Meridith study. For a detailed description of the study, please visit our Web site at Brandt, at (916) 703-0320. http://app.mindinstitute.org, or contact project manager Lou Ann Barnett, Ph.D., at (916) 734-0441 or [email protected].

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Disc jockeys team up to raise autism awareness

Pat Still and Tom Mailey have done as much as anyone to elevate public awareness of the M.I.N.D. Institute during the past several years. And they’re not even on the payroll. The DJs, known to their radio listeners for the past 15 years simply as “Pat and Tom,” host the 5 a.m. to 10 a.m. slot weekdays on Sacramento country music station KNCI, 105.1 FM. Between hits by Brad Paisley, Martina McBride and Keith Urban, they engage their audience with updates about popular performers, comments about current events and zany antics. Yes, they conducted an on-air interview with a guy named Uncle KNCI morning disc jockeys Pat Still and Tom Mailey. Booger, who invented an emergency porta-potty that attaches to a trailer – together hosted the public ribbon-cut- hitch. And they demonstrated the ting ceremony. parental difficulties of assembling tiny “Dimitri is a smart little guy, The Stills were intrigued by the toys given away with fast-food kids’ but he doesn’t communicate M.I.N.D. Institute because they had meals. Mailey credibly impersonates the way that you and I become suspicious about Dimitri’s with- Carol Channing’s voice, and Still can drawn behavior. Their other son, Lucas, imitate Shaggy, the cartoon dog. do. We credit the team of was 3 years old when Dimitri was born. But Pat and Tom also are staunch tutors at his school and the “By the time Dimitri reached the age of advocates of worthy causes. They 3 months, he still wouldn’t look directly publicize and participate in fundrais- therapists at the M.I.N.D. at us, and never made eye contact with ing events that have increased public Institute for the progress us,” Still said. “He didn’t react when we awareness and support of the M.I.N.D. that he has made.” called his name, so we suspected deafness, Institute. Both speak passionately but tests when he was 11 months old – Pat Still about it because they have more than a confirmed that he could hear just fine.” passing interest. Only through evaluation at the M.I.N.D. Mailey’s 10-year-old son, Joey, has channel 58. Gardner and her husband Institute was the diagnosis of autism con- attention-deficit/hyperactivity disorder Chuck, whose son Chas has autism, were firmed when Dimitri was 19 months old. (ADHD) and a mild hint of Tourette among the founding parents who helped “Dimitri is a smart little guy, but he syndrome. Still’s 8-year-old son Dimitri create the M.I.N.D. Institute. doesn’t communicate the way that you has autism. Both boys have been Back in 2000, Pat and D’Anne partici- and I do. We credit the team of tutors treated at the M.I.N.D. Institute. Still pated in a walk, along with Dimitri in a at his school and the therapists at the in particular has been involved with stroller, to raise funds for the M.I.N.D. M.I.N.D. Institute for the progress that he the M.I.N.D. Institute since its forma- Institute. The following year, Still took has made.” tive days, encouraged by newscaster part in the ground-breaking ceremony Most recently, Pat and Tom co-hosted Sarah Gardner. Still’s wife D’Anne for the facility. When construction of the their third annual Clint Howard Celebrity worked with Gardner as a producer M.I.N.D. Institute was completed in April Wiffle Ball Challenge, proceeds of which and camera operator for television 2003, Still, Sarah Gardner and actor David benefited the M.I.N.D. Institute. stations KCRA channel 3 and KQCA Gallagher – whose brother has autism (continued next page)

10 UC DAVIS M.I.N.D. INSTITUTE P H IL A NT H ROPY

“The Wiffle tournament doesn’t raise Vicki, also have two other children: I would turn somersaults for that,” Pat a lot of money, but it has raised public another son, Sam, and a daughter, Emma. Still confided. “One of our greatest fears awareness and given us an opportunity Mailey describes his family’s involve- is that responsibility for Dimitri will come to talk about the M.I.N.D. Institute,” ment in M.I.N.D. Institute activities as down around the neck of his brother Mailey said. “We have plenty of breaks much more ancillary than that of Pat and when we’re gone. When I see a homeless [between songs] when we can goof D’Anne Still. person, I think, dear God, I hope that is around and scratch the itch to be 12 Even as Dimitri has begun learning not what lies in store for my son.” years old again, but we also have lots of to cope with the world around him, his The Stills take solace in a slogan that other breaks in which we can do some- parents have undergone changes as well. Sacramento advertising executive Dave thing for the community,” Mailey said. “Early on, our greatest hope was that Mering created for a series of M.I.N.D. The Tourette syndrome manifesta- Dimitri eventually could live a normal life. Institute public service announcements: tions that Mailey’s son Joey exhibits That hope is still there, but we now know “It takes a heart to cure a mind.” are subtle facial muscle movements. we have to adjust our sights and re-evalu- Speaking for his friend, Mailey adds, Although they’re irritating to Joey, ate continuously. If he could just some- “Pat believes if a cure for autism is ever Mailey said the movements are barely how survive even through assisted living found, that discovery will be made at the perceptible to others. He and his wife, to enable him to do something productive, M.I.N.D. Institute.”

M.I.N.D. INSTITUTE 10TH ANNIvERSARY CElEbRATION

THE JOURNEY OF THE M.I.N.D. A PROMISE FOR THE FUTURE.

Third annual gala benefiting the UC DAvIS M.I.N.D. INSTITUTE. Saturday, March 29

As we celebrate 10 years of progress and growth, join us in honoring the vision of the founding families and the State of California. The evening includes a gourmet dinner, fine wines, select auction, dancing to Hip Service, and inspiration from a special guest.

Contact Terri Contenti at 916.703.0289 for tickets and more information

UC DAVIS M.I.N.D. INSTITUTE 11 L e a D E R s h IP

Executive director’s message

This year, art research facility to evaluate innovative different, yet parallel, paths in the urgent the UC Davis treatments for these disorders. task of uncovering the causes of autism. M.I.N.D. Institute In this issue of M.I.N.D. Matters, We also introduce you to two new celebrates its 10th we highlight some of our innovative M.I.N.D. Institute faculty, Stephen C. anniversary. We research, rich faculty collaborations, and Noctor and Clifford Saron. Steve is an have accomplished dedicated families and staff who make assistant professor of psychiatry and much for such up the unique and successful enterprise behavioral sciences who studies cell a relatively young institution, that is the M.I.N.D. Institute. These growth and migration in the develop- assembling a broad, multidisciplinary research articles bring you up-to-date ing brain. Cliff is an assistant research team of clinicians, scientists and on the complementary aspects of work scientist who is investigating responses dedicated staff who are conducting conducted by Center for Neuroscience to sensory issues in children with autism and publishing leading-edge research associate professor Kimberley McAllister spectrum disorders. and increasingly becoming the “go-to” and M.I.N.D. Institute professor Judy In our philanthropy section, we experts for federal research agencies, Van de Water, who are further exploring give you a peek inside the professional state and federal policy-makers, and the links among autism, the immune and personal lives of two prominent journalists covering health, science system and the brain. Kim is investigating Sacramento DJs, Pat Still and Tom and the environment for prominent whether environmental factors can trigger Mailey, both of whom have sons with media outlets. changes in key immune system mol- neurodevelopmental disorders and play We are fortunate to have a dedi- ecules that might contribute to autism. important roles in raising awareness about cated community of children, families Judy is studying what happens during autism and the M.I.N.D. Institute. and donors who partner with us pregnancy that may affect neurodevelop- We cordially invite you to participate to find better treatment strategies ment, including whether the mothers of in our 10th annual gala, scheduled for and, ultimately cures, for a host of children with autism have autoantibodies March 29, 2008. Join us as we celebrate neurodevelopmental disorders, from that affect fetal brain proteins. NO NEW the progress and growth of the M.I.N.D. autism and attention deficit/hyperac- PARAGRAPH…..We also highlight the Institute and honor the vision of our tivity disorder to fragile X and Tourette important animal studies conducted by founding families. syndromes. They are also helping us neurological surgery professor Robert Robert L. Hendren, D.O. to generate the funds and support Berman and M.I.N.D. Institute Research Executive Director needed to build a second state-of-the- Director David Amaral, who are taking UC Davis M.I.N.D. Institute

Non-Profit Org. U.S. Postage M.I.N.D. Matters is a publication of PAID the UC Davis M.I.N.D. Institute. 2825 50th Street UC Davis Editor: David G. Amaral, Ph.D. Sacramento, CA 95817

Managing editor: Laura R. Lacy, Ph.D. (6463) Contributing editor: Carole Gan Address service requested Executive Director: Robert Hendren, D.O. Research Director: David G. Amaral, Ph.D. Clinical Programs Director: Robin Hansen, M.D. Medical Director: Randi Hagerman, M.D. Chief Administrative Officer: Kathy Lelevier E-mail questions to: [email protected] Telephone: (916) 703-0280 Web site: www.mindinstitute.org

The University of California does not discriminate in any of its policies, procedures or practices. The university is an affirmative action/equal opportunity employer.