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Reveling In The Ties That Bind Us
A Profile of James F. Leckman, M.D.
By Robin Eisner

Imagine a new mother. The woman looks adoringly at her baby girl she is cradling in her arms. The baby’s eyes light up and her lips form a smile. For a moment, the mother worries she is going to drop the baby, but the thought passes. She kisses the baby and starts talking to her about how beautiful she is and describes the day’s events: a bath; eating; shopping; playing with some toys; a nap; more eating; and daddy coming home for dinner.

But three miles away, a single mother recovering from methamphetamine abuse, towers over her infant girl lying on the floor. The baby starts to cry and the mother mocks her cries, yelling at her to shut up or else she won’t get food. The mother smokes a cigarette and drops ashes on the child. She starts to laugh and talk about the power she has over the tiny creature.

These two scenarios represent extremes of early experiences that probably will lead to different outcomes, for a variety of reasons. However, genetic influences, such as a predisposition to depression in the first child, or non-genetic influences, such as a positive role model early in life for the second child, could affect the “expected” life trajectory. Independent of nature or nurture, that primal bond between parent and infant is vital to the child’s development. But many aspects of this attachment remain mysterious.

Dr. James F. Leckman, Neison Harris Professor of Child Psychiatry, Psychology and Pediatrics at Yale and director of research there for the Child Study Center, hopes to use the latest techniques in brain imaging to uncover how parents “fall in love” with their newborns, continuing the progress he has made over the past decade studying how humans form attachments. His goal: to better understand “healthy” early affiliations and to develop interventions for children in less nurturing conditions.

Very few people have the clinical, research and teaching experience, the empathy for the human condition, and the curiosity Dr. Leckman has to explore such a fundamental question as human attachment. He is a world-renowned child psychiatrist and patient-oriented clinical investigator with unique expertise in the evaluation of Tourette’s syndrome and early-onset obsessive-compulsive disorder. Colleagues routinely select him as one of America’s best doctors. Author or co-author of seven books, more than 250 articles in peer reviewed journals and 115 book chapters, Dr. Leckman is in the top one percent of publishing researchers and one of the world’s most cited researchers in psychology and psychiatry.

In addition to “bonding” research, Dr. Leckman leads many collaborative and interdisciplinary research projects, such as investigating how genes and the environment interact in the development of Tourette’s syndrome and early-onset obsessive-compulsive disorder. He recently obtained a National Institute of Mental Health (NIMH) grant to conduct a five-year study to evaluate psychosocial stress and auto-immunity in the progression of these diseases. He and colleagues found changes in the number of GABAergic neurons in postmortem brains of Tourette’s patients compared with controls. That finding and other positive results with deep brain stimulation for refractory Tourette’s syndrome patients has led him to use magnetoelectroencephalography to study abnormal neural oscillations in Tourette’s.

Recently, Dr. Leckman became involved in using evolutionary principles to understand psychopathology. In this line of inquiry, he has asked why intrusive worrisome thoughts about family members often associated with obsessive-compulsives have survived in human history and why less extreme versions of these thoughts might enable survival of the human species. Work in this area led to a course he teaches in Yale’s psychology department with Linda Mayes on “Love and Attachment,” which students rate highly.

In addition to pursuing his projects, he has been director of research at the Yale Child Study Center since 1983. The center is a major child psychiatric research institute, supported by many National Institutes of Health grants. “One of the guiding principles of the center is that every clinical research project benefits patients,” Dr. Leckman says. At the center, he has promoted research of normal development to understand clinical disorders. The center also focuses on the multigenerational role of the transmission of risk and protective factors and the often complementary roles of environmental and constitutional factors in the pathogenesis of child psychiatric disorders. Since 1983, he also has been the associate director of the General Clinical Research Center at Yale, which carries out patient-oriented research.

Dr. Leckman also values educating the next generation of psychiatrist researchers. For the past 16 years he directed a post-doctoral training program at Yale and has mentored students who have become independent investigators. For the past 10 years, he also has received support from the Klingenstein Third Generation Foundation to expose medical students to the challenges of caring for children and adolescents with mental, behavioral and developmental disorders and, when possible, encourage them to pursue careers in research.

He has served on many national committees, including some to revamp the training of child psychiatrists. Most recently, in 2004, he was asked by NIMH director Dr. Thomas Insel to co-chair the National Psychiatry Training Council. The council stressed that model psychiatry residency programs include early research training for psychiatrists and support for their becoming independent investigators. Between 2001 and 2002, he also served on two NIMH committees: one charged with developing a national plan for research on child and adolescent mental disorders and another on creating a strategic plan for research on mood disorders.

Apparently working non-stop, Dr. Leckman serves on the editorial boards of the major journals in child psychiatry and has received many professional honors and awards. NARSAD is honored to have him on its Scientific Council, helping to shape the future of psychiatric research. “I often tell investigators to apply to NARSAD for funding,” says Dr. Leckman, a recipient of NARSAD support in 1993. Indeed over the past decade more than 15 NARSAD awards have gone to his trainees and colleagues at the Yale Child Study Center.

Dr. Leckman graduated in 1969 from the College of Wooster in Ohio with a degree in chemistry and philosophy. He obtained his medical degree from the University of New Mexico School of Medicine in Albuquerque. He interned at the U.S. Public Health Service Marine Hospital from 1973 to 1974, was a clinical associate in the psychogenetics section of the NIMH’s adult psychiatry branch from 1974 to 1976, and pursued a psychiatry residency at Yale from 1976 until 1979. He was a postdoctoral fellow in child psychiatry at Yale from 1979 until 1980. For most of his career he has been at Yale, but has taken three sabbaticals: in 1987/8 in Yale’s biology department to study molecular genetics and developmental biology; in 1997, at the Neurosciences Institute in San Diego to study evolutionary biology; and in 1998, at the University of Cambridge to study molecular ethology (the scientific study of animal behavior). He also is a psychoanalyst.

While his early scientific/medical career focused on depression and schizophrenia, his recent study of the parental-child bond began as an outgrowth of his work in the late 1980s with Tourette’s syndrome and obsessive-compulsive disorder. At that time, he and a collaborator tried to determine if certain compounds in the cerebrospinal fluid of these patients were either higher or lower than in healthy subjects. In 1992, they reported that some individuals with obsessive-compulsive disorder had higher levels of oxytocin, a hormone that stimulates nursing in mothers, causes uterine contractions during labor and is sometimes used by doctors to induce labor.

Dr. Leckman then began to investigate what role oxytocin, which is involved in parent-child bonding and relationship formation, might have in obsessive-compulsive behavior. He hypothesized that some obsessive-compulsive behaviors are extremes of normal behaviors mediated by oxytocin and related systems, and that some cognitive, bonding and sexual behaviors are evolutionarily conserved and contain elements similar to features of obsessive-compulsive disorder. Dr. Leckman says that being a new parent creates a heightened sensitivity that is normal. “If early humans didn’t pay close attention to a clean and protected environment for offspring, our ancestors might not have made it,” Dr. Leckman says. Obsessive thoughts might be an adaptive trait, which if dysregulated, could lead to psychopathological conditions, he says.

As a psychoanalyst he turned his exploration upon himself, remembering his own worried thoughts when his wife was pregnant and developed a cough. He also considered psychologist Donald Winnicott’s observation of primary maternal preoccupation, that period in the first weeks of a baby’s life when a mother is completely absorbed in the infant.

So Dr. Leckman began a study of 40 new mothers and fathers to assess the kinds of thoughts they had during pregnancy, two weeks after birth and three to four months after birth. In 1999, he reported that parents during the first two weeks after birth experience anxious and intrusive thoughts that lead them to behaviors that prevent harm to their infant. Such thoughts range from worrying about child’s illnesses, to fear of dropping a baby, to cleanliness of the environment. The feelings resemble obsessive- compulsive disorder thought patterns that lead to stereotyped behaviors.

He also used his proficiency in molecular biology of neural development, to characterize the human copy of a gene, called Orthopedia, that is involved in forming certain parts of the brain that are essential for bonding to occur. This gene sets the stage for the development of the cells in the brain that make oxytocin. He then used funding from NARSAD to screen DNA specimens from patients with obsessive-compulsive disorder and autism for mutations in this gene. Autism is relevant as it likely represents a failure of close interpersonal bonding to occur. He also has analyzed each of the 10 or so genes identified in genetic knockout mice that are known to cause deficiencies in either maternal behavior or pup responsiveness.

Dr. Leckman, with his colleagues James Swain (also a recent recipient of a NARSAD grant) and Linda Mayes, has now repeated the study of the thoughts of new parents with 30 additional parents and included brain imaging: observing what parts of parents’ brains were activated when they heard tapes of their baby or another baby crying and when they looked at pictures of their baby or others’ babies. He added the imaging to follow up on a result of the first study in which he found many parents said they thought their child was perfect, when asked. “Besides new parents having a heightened sensitivity of threat to their child, they also idealized the baby,” Dr. Leckman says. When he analyzed the brain imaging data, he found that first-time parents seeing pictures of their babies during the first two weeks had activated brain regions associated with stress and anxiety, but in three to four months the pictures activated regions of the brain associated with bonding and rewards. “The result probably reflects a transformation of the parent to the loving of the infant that occurs within that two week period,” Dr. Leckman says. Veteran parents, however, never had the anxiety response at two weeks, but had the bonding and reward re-gions of their brains activated.

Dr. Leckman would now like to employ different brain imaging methods, called magnetoencephalography and high-density electroencephalography, and cardiac measurements, to study if parents and babies have shared brain and cardiac patterns. He believes that “the interpersonal synchrony in neural and cardiac oscillations may reveal the transformation from anxiety to love that occurs in new parents.” By understanding this vital attachment, which seems to be associated with obsessive-compulsive type behaviors, he hopes to gain a better understanding of love and bonding — an essential aspect of our humanity — and what may happen when we don’t connect.


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Announcements
2006/2007 NARSAD Grant Deadlines:

2007 Young Investigator applications accepted: Applications available June 1, 2006 - July 25, 2006

2007 Staglin Award: Applications available on-line September, 2006

2006 Independent Investigator Applications: Deadline has passed (March 6, 2006)

2006 Independent Investigator Letters of Acceptance/Declination Sent: August, 2006

2006 Independent Investigator Earliest Start Date: September 15, 2006

2007 Distinguished Investigator 1st Round applications: Deadline has passed (May 15, 2006)

2007 Distinguished Investigator 1st Round declinations and invitations to 2nd round: September 2006

2007 Distinguished Investigator Earliest Start Date: May 1, 2007

2006 Distinguished Investigator Letters of Acceptance/Declination
Sent: March, 2006

2006 Staglin Award Letters of Acceptance/Declination Sent: March, 2006

2006 Young Investigator Letters of Acceptance/Declination
Sent: March, 2006



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