2011 Program

The 2011 On the Shoulders of Giants Scientific Symposium honoring Jerome Kagan, PhD, and Judith L. Rapoport, MD, took place on September 14, 2011, at the New York Academy of Medicine. The symposium concluded with ABC’s Nightline anchor Cynthia McFadden moderating a roundtable discussion that focused on Drs. Kagan’s and Rapoport’s personal and professional journeys.

About the Presentations

Childhood Onset Schizophrenia: Rare But Worth Studying
Judith L. Rapoport, MD
Across all of medicine and pediatrics, the study of very early-onset forms of illness has contributed much to our knowledge of the underlying biology and genetics of the disease. For 20 years the NIMH has been observing children and adolescents with onset of schizophrenia before age 13, a rare and severe form of psychosis. Several striking results have emerged. Children with schizophrenia have a high rate of very early problems with speech, language and motor development, and almost one-third had symptoms of autism spectrum disorder. Brain abnormalities were more striking than in adult-onset patients, and were progressive. Genetic studies showed a high rate of rare deletions or duplications in risk genes for the disorder. Finally, many treatment refractory children responded to clozapine as has been seen in adults. Ongoing studies of the biology of the illness will be discussed.

When Noise Is Not Noise: The Role of Spontaneous Fluctuations in Brain Function Throughout Life
Xavier Castellanos, MD
Throughout her storied career, Judith Rapoport has overturned the scientific dogma of the day on multiple occasions. At the NIMH she has always encouraged high-risk/high-reward scientific inquiry. Dr. Castellanos worked with Dr. Rapoport for a decade, during which they initiated a landmark longitudinal study of brain structure in people with ADHD that continues to be remarkably productive under her leadership. Inspired by Dr. Rapoport’s encouragement to “always go for the jugular,” Dr. Castellanos hypothesized that ultra-low frequency spontaneous fluctuations in the brain reveal fundamental physiological principles underpinning brain self-organization, and that examining such low frequencies offers a path to understanding the physiology of ADHD. This link between behavioral and cognitive inconsistency and brain architecture is now being actively investigated.

Accelerating the Pace of Psychiatric Research: The Promise of New Models and Methods
Michael Milham, MD, PhD
Over years of working together, Xavier Castellanos has repeatedly challenged Dr. Milham to think outside the box and stressed the need to change science at the cultural level, not just at the bench. Psychiatry remains the only field of medicine without objective biological measures of the presence of illness or treatment response. Dr. Milham will discuss recent advances in imaging methodologies and their potential to lead to the development of clinical tools to aid in diagnosis, treatment selection and assessment. He will also discuss recent efforts to promote open neuroscience as a means of accelerating the pace of scientific discovery, in particular the 1000 Functional Connectome Project and the International Neuroimaging Data-Sharing Initiative. Co-founded by Dr. Milham, these endeavors have distributed thousands of brain images to researchers globally, yielding novel insights into brain architecture and the impact of psychiatric disorders such as ADHD.

The Contribution of Temperamental Biases to Adult Development
Jerome Kagan, PhD
Dr. Kagan will present conclusions on a study of a group of infants followed from 4 months to age 18 years:

• The high reactive infants are biased to become shy, timid toddlers. As they grow, their timidity is muted somewhat, but they develop unrealistic anxieties. They are at higher than average risk for social anxiety and depression during adolescence. Brain imaging reveals a thicker cortex in a small area in the ventromedial prefrontal region of the right hemisphere. They also show shallow habituation of the BOLD signal during repetitions of unfamiliar scenes.
• The low reactives become sociable, fearless toddlers and as adolescents are free of unrealistic worries. Importantly, the few low reactives who reported social anxiety or depression (mainly females) did not possess a thicker cortex in the ventromedial area and did not show a large BOLD signal to the amygdala during the unexpected scenes. Clinicians could use these biological markers to differentiate adolescents with the same DSM diagnosis.

Is the Glass Half Empty or Half Full? Behaviorally Inhibited Children Learn About the Social World
Nathan A. Fox, PhD
Jerome Kagan first described the temperament of behavioral inhibition in 1984 and he linked behavioral and physiological profiles to circuitry in the brain that underlie responses to novelty and fear. Infants with the temperament of behavioral inhibition display heightened motor reactivity and emotional distress when confronted with novel or unfamiliar events. As they get older, some display social reticence, withdrawal and developing anxiety, while others present as quiet, thoughtful and reflective. Dr. Fox will discuss mechanisms that contribute to the developmental trajectories of behaviorally inhibited children, including research on the importance of brain systems underlying motivations to approach or withdraw. He will also tie these findings to the significant contributions that Dr. Kagan has made to our understanding of the biology of individual differences.

Temperament’s Fingerprint: Attention as a Mechanism for Socioemotional Development
Koraly Perez-Edgar, PhD
As first described by Dr. Jerome Kagan, behavioral inhibition is a biologically-based temperamental trait marked by sensitivity to novelty and discomfort in social situations. It is also one of the strongest markers of risk for anxiety. Yet, for most children, maturational and environmental forces work in tandem to ameliorate this risk. A growing literature suggests that attentional biases to evocative stimuli may play a causal role in emerging anxiety. Specifically, attention biases to threat are evident in both children and adults with anxiety and children temperamentally at risk for developing anxiety. There is a systematic relation between these biases and risk at the behavioral, genetic and neural level. This attention bias also moderates the emergence of social withdrawal. Building on the work of Drs. Kagan and Fox, Dr. Pérez-Edgar will examine this pattern within a larger biobehavioral context reflected in the neural and genetic correlates of inhibition and anxiety. 

About the Presenters

Judith L. Rapoport, MD, is a graduate of Swarthmore College and Harvard Medical School. Since 1986 she has been Chief of the Child Psychiatry Branch at the National Institute of Mental Health in Bethesda, MD. Her clinical research training was at the Massachusetts Mental Health Center in Boston and St. Elizabeth’s Hospital in Washington, DC. Research training included two years at the Karolinska Institute in Stockholm. Dr. Rapoport’s work has been influential in the areas of diagnosis in child psychiatry, attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and childhood-onset schizophrenia. She is the author or coauthor of over 300 papers and five books. Her book on OCD, The Boy Who Couldn’t Stop Washing, was a New York Times Best Seller. She is a member of the Institute of Medicine and a Fellow of the American Academy of Arts and Sciences.

Jerome Kagan, PhD, is Emeritus Professor of Psychology at Harvard University. He has studied cognitive and emotional development for over 50 years. During the past 25 years he and colleagues have concentrated on the role of temperament in development. Kagan is a member of the Institute of Medicine of the National Academy of Sciences and a Fellow of the American Academy of Arts and Sciences. He has been awarded the Distinguished Scientist Award from the American Psychological Association and the Society for Research in Child Development as well as the Child Mind Institute. He has authored or co-authored more than 300 papers and more than 15 books. His major books include: Birth to Maturity (with Howard Moss), Galen’s Prophecy, The Nature of the Child, Infancy (with Richard Kearsley and Philip Zelazo), Three Seductive Ideas, A Young Mind in a Growing Brain (with Norbert Herschkowitz), The Long Shadow of Temperament (with Nancy Snidman), What Is Emotion? An Argument for Mind, The Three Cultures, and in 2012, Recalcitrant Ghosts.

Xavier Castellanos, MD, a renowned neuroscientist, has devoted his career to developing innovative research techniques to deepen our understanding of both healthy and pathological brain processes. Dr. Castellanos is director of the NYU Child Study Center’s Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience and the Brooke and Daniel Neidich Professor of Child and Adolescent Psychiatry at the NYU School of Medicine, among other appointments. Dr. Castellanos worked for 10 years as chief of the ADHD Research Unit at the NIMH. As co-chair of the American Psychiatric Association Workgroup on ADHD and Disruptive Behavior Disorders, he is a key contributor to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). His work has been published in the Journal of the American Medical Association, the American Journal of Psychiatry and Biological Psychiatry, among others.

Michael P. Milham, MD, PhD, is an internationally recognized neuroscience researcher, a gifted and caring clinician, and the founding director of the Center for the Developing Brain at the Child Mind Institute. Dr. Milham is one of our nation’s most prolific scientists, with over 100 articles published since 2000, and an average of about 10 publications per year during the past three years. He has published in the most scientifically respected journals, including the American Journal of Psychiatry, Journal of Neuroscience, Biological Psychiatry and the Archive of General Psychiatry. Dr. Milham’s innovative research techniques signal a sea change in the field and a revolution in discovery science. 

Nathan A. Fox, PhD, is a Distinguished University Professor in the Department of Human Development at the University of Maryland College Park. Professor Fox has completed research on the biological bases of social and emotional behavior, developing methods for assessing brain activity in infants and young children during tasks designed to elicit a range of emotions. His work is funded by the National Institutes of Health and he was awarded a MERIT award for his research program examining the social and emotional development of young children. Professor Fox has served as associate editor of the journals Developmental Psychology and Psychophysiology and as editor of the journal Infant Behavior and Development. He is currently associate editor of the International Journal of Behavioral Development. Dr. Fox was awarded a Distinguished Investigator grant from the National Association for Research in Schizophrenia and Depression (NARSAD) and was appointed a Fellow of the American Association for the Advancement of Science in 2008.

Koraly Perez-Edgar, PhD, is an associate professor of psychology at The Pennsylvania State University. She received her A.B. from Dartmouth College and her MA and PhD from Harvard University, under the direction of Dr. Jerome Kagan. She received post-doctoral training under the direction of Dr. Nathan A. Fox at the University of Maryland, College Park, and Dr. Daniel S. Pine at the National Institute of Mental Health. Dr. Pérez-Edgar’s research focuses on the relations between temperament, attention and psychopathology, particularly anxiety. In conducting her work, Dr. Pérez-Edgar has taken a multi-method approach involving direct observation of behavior, cognitive functioning, psychophysiology and neuroimaging. Dr. Perez- Edgar is the recipient of numerous awards including an NIMH BRAINS Award, an NIMH K01 Career Development Award, a NARSAD Young Investigator Award, an ADAA Career Development Award, a Ford Foundation Dissertation Fellowship and an NSF Graduate Fellowship.