Yesterday the Child Mind Institute hosted On the Shoulders of Giants, a celebration of Jerome Kagan, PhD, and Judith L. Rapoport, MD, the two recipients of the Child Mind Institute 2011 Distinguished Scientist Awards. Drs. Kagan and Rapoport, along with two generations of their protégés, presented their transformative research in child mental health.

Dr. Rapoport, Founder and Chief of the Child Psychiatry Branch at the National Institute of Mental Health, led a spirited tour of the past half-century in child and adolescent psychiatry and focused on the insight that can be derived from the study of even rare disorders, like child-onset schizophrenia. She pointed out the great contributions of early-onset research in breast cancer and Alzheimer’s, and held out hope for revolutionary breakthroughs in schizophrenia. “There’s some evidence that age of onset is a separate factor in itself,” Dr. Rapoport told the audience. “If you could figure out what triggers the onset of a disorder,” you could mitigate the genetic risk.

Dr. Rapoport lauded advances in non-radiation brain imaging, like functional magnetic resonance imaging (fMRI), that she said “changed a generation of research,” and Xavier Castellanos, MD, spoke to that after thanking her for teaching him “to think like a scientist” during their years of working together.

Dr. Castellanos, Brooke and Daniel Neidich Professor of Child and Adolescent Psychiatry at the NYU School of Medicine, recounted that after years of searching in vain for a “static neuropsychological deficit in ADHD,” he decided instead to look for inconsistencies on a larger scale. This led him to discover a low-frequency “rhythmicity” of brain activity unfolding over the course of minutes, tying regions near and far together and accounting for the majority of energy used. “It behooves us to attend to the music of the brain,” he said, and the promise of large-scale imaging studies going forward is to build a map of typical relationships in the brain and simultaneously reveal the inconsistencies that represent psychopathology. Once we understand the physiology, structure, and function of the brain, he says, “diagnosis really follows, and the treatment opportunities emerge.”

“The way life works with Xavier,” said Michael P. Milham, MD, PhD, “is Xavier points in a direction and, admittedly, at first I usually look at him a little bewildered and wonder, ‘Why?'” Dr. Milham, director of the Center for the Developing Brain at the Child Mind Institute, is now fully on board with the investigation into low-frequency brain oscillations and is pushing the boundaries of the scientific culture to obtain what Dr. Castellanos calls “large, harmonized aggregations of data” through massive collaboration and the free and open exchange of information. In the molecular genetics community, Dr. Milham said, “every day they just upload their data and they just share it.” He was initially skeptical that this could happen in the neuroimaging world. “But you start to think to yourself, ‘Why not?'” Now the goal is to push data aggregation and discovery science towards developing “objective, imaging-based measures of psychiatric illness.”

Psychiatry needs “something to help us with diagnosis…something to guide us in treatment, and also an objective means of monitoring treatment response. As a child psychiatrist it’s a particularly challenging situation where you can’t always ask the child, ‘Did this medicine help or not?'” And progress is imperative. “These are dreams that we need to keep moving towards, because the truth of the matter is that the morbidity and mortality, the costs financially and in human suffering with psychiatric illness is too great.”

Dr. Kagan, the Daniel and Amy Starch Professor of Psychology Emeritus of Harvard University, narrated the sea change in developmental psychology over the past half-century and more, recalling that at the beginning of his career child psychologists were convinced that environment and family were all that shaped a child’s personality—that infants were “blank slates.” After an “epiphany” observing children in a Guatemalan village, he began to study temperament, what he calls the “biologically based disposition for certain moods and behavior profiles.” His research led to an understanding that the behavior of infants in the presence of novelty—whether they are “high reactive” (crying and squirming) or “low reactive” (giggling and engaged)—correlates to an increased or decreased likelihood to be anxious and solitary as they grow. Most kids turn out fine, Dr. Kagan said, as temperament simply indicates a bias for certain behaviors. “The environment is working,” he said.

The biological basis of temperament becomes quite important when the behaviors are clinically significant. If you really want to understand a particular case of psychiatric illness, “you’ve got to get some biology.” Although a person’s personality is “malleable,” as Dr. Kagan puts it, the biological temperament at the top of the “cascade” never goes away. “If you drop some black ink in a vessel of glycerin and stir it, the black ink disappears—but it’s there.”

“Go and find the neurobiology,” Dr. Kagan exhorted the students in the audience—which is exactly what his protégé, Nathan Fox, PhD, did after spirited encouragement. “He said that very few high reactives become exuberant,” said Dr. Fox of Dr. Kagan, “but I don’t know if that’s true about Jerry.” While Dr. Kagan focuses on the amygdala as the biological center of temperament, Dr. Fox, Distinguished University Professor at the University of Maryland, has located a different locus of neurobiological action in the “reward circuitry” of the brain, including the caudate nucleus and the striatum. He has found that low-reactive infants, who become “behaviorally inhibited” children, actually avoid punishment instead of approaching reward. But he also doesn’t make value judgments on these sub-clinical behaviors. In the Q&A session after the talk, an audience member asked how different educational models might disinhibit these kids. “I think that there’s nothing wrong with being behaviorally inhibited,” Dr. Fox replied. “That in fact there should be a place in our culture and our society for children, adolescents, and adults who are more reserved, and who tend not to be as outgoing and exuberant as many other children tend to be.”

“What we’ve been trying to do in my lab,” began Koraly Perez-Edgar, PhD, “based on the guidance I got from both Jerry and Nathan, is the notion of empowering the child. What role is the child bringing into his environment and into his world?” Dr. Perez-Edgar focused on yet another contributor to inhibition, and coined perhaps the most memorable phrase of the symposium: the developmental tether of attention. “Babies are born into the world with these jagged edges, these traits, these vulnerabilities, these risk factors that kind of stick out,” said Dr. Perez-Edgar, associate professor at The Pennsylvania State University. “And almost immediately the world begins to smooth out those edges—either maturationally, environmentally, socially, so that over the course of development most children turn out just fine.” But, she says, “for some subsection of our population, whether it be OCD, schizophrenia, social anxiety those jagged edges remain. So my question is, What are these developmental tethers that bind these children to those initial proclivities?”

Dr. Perez-Edgar’s research has indicated that it is an attentional tether, and that an inability to focus attention selectively—a sort of hypervigilance—is what turns behavioral inhibition into social withdrawal. But this is still at basis a biological issue, one that interacts with the environment to create a persona, and perhaps a disorder. “The ancient Greeks talked about these types of individuals, with melancholic, sanguine, choleric, phlegmatic temperaments that come from underlying biles and humors that interact,” Dr. Perez-Edgar noted. “And these are the same notions we use today. But if we were to use the phrase ‘black bile’ we’d never get funded. So we talk about neurotransmitters.”

At the roundtable discussion following the talks, Drs. Rapoport and Kagan opened up to moderator Cynthia McFadden, sharing both ruminations on past struggles and great hope for the future of developmental research, child and adolescent psychiatry, and the welfare of children everywhere. Dr. Kagan discoursed on the transformative power of knowledge for troubled people. “Sometimes new facts, if you’re ready, can turn you around. Just to understand can dilute anxiety in a major way. That’s what therapists do: They help you understand.”

But that knowledge is often hard to come by, and the perception of progress doesn’t always jibe with reality. Dr. Rapaport talked about the causes of psychiatric illness: “What’s been frustrating is that it’s enough to say words like ‘gene-environment interaction’ and ‘epistasis’ but we’re so lacking for specifics that it doesn’t really tell you much more than ‘oedipal complex.’ You know, we all have gene-environment interactions; it’s still at a frustrating point where that’s become a general truism, but it’s a kind of apple pie concept and we really need badly—and people are indeed working on this—to get to things that are more specific.”

Regardless of that sober assessment, both Dr. Rapoport and Dr. Kagan are optimistic about the future. Dr. Rapoport has faith in the technology and the massive data processing efforts that are going on as we speak. Though psychiatry research has long been focused on pharmacology, that area has slowed recently. “What the field has done is to look at other things.” And Dr. Kagan sees a melding of disciplines somewhere in the future. “When we can join the person’s psychological understanding of their lives, their feelings, their history, with their biology, we’re going to see tremendous advances.”

What started them on their journeys? “When I was 12 years old I saw the original black and white version of Goodbye, Mr. Chips with Robert Donat,” admitted Dr. Kagan.

And Dr. Rapaport?

“Accidentally, perhaps.”