Developmental
Psychobiology
Myron A. Hofer, M.D.
Chief of Psychiatric Research
Gordon A. Barr, Ph.D.,
Research Scientist V
Susan A. Brunelli, Ph.D.,
Research Scientist IV
William P. Fifer, Ph.D.,
Research Scientist V
Jay A. Gingrich, M.D., Ph.D.,
Research Associate
Michael M. Myers, Ph.D.,
Research Scientist V
Jonathan Polan, M.D.,
Research Associate
Harry N. Shair, Ph.D.,
Research Scientist IV
Christoph P. Weidenmayer, Ph.D.,
Research Associate
This department's research focuses on the processes involved in the development of behavior and its underlying biological systems. We study how natural events and stressful experiences interact with genetic mechanisms to alter the course of normal development. Investigation of these developmental processes provides important clues to the origins of a wide range of clinical conditions. Projects in the department are multidisciplinary, ranging from targeted gene deletion of neurotransmitter receptors in mice to the effects of prenatal experience on human fetal and infant behavior.
Departmental Research
Fetal Behavior and Intrauterine Influences Following his discovery that newborn babies recognize and prefer their own mother's voice within a few hours of birth Dr. Fifer, in collaboration with Dr. Myers, has extended these observations into a program of research on the effects of fetal stimulation on brain/behavior development. Dr. Catherine Monk, a Sackler Research Fellow, together with Drs. Myers, Fifer, and Dr. Richard Sloan from the Department of Behavioral Medicine has expanded this research to include the influence of maternal emotional states on the fetus. Studies investigating associations between maternal depression and anxiety on fetal and infant development have been funded by the March of Dimes and the National Alliance for Research on Schizophrenia and Depression. Drs. Fifer and Myers incorporate similar approaches in a continuing study of early markers of risk for Developmental Disorders and Sudden Infant Death (SIDS). This NICHD funded study involves information and technology exchange between researchers at the New York State Psychiatric Institute and Co-Investigators at the Pine Ridge Indian Reservation in South Dakota. A further extension of this work with researchers in Department of Pediatrics has uncovered important new relationships between sleep states, sleeping position, and the developing nervous system in prematurely born infants.
Mechanisms of Early Attachment and Separation Dr. H. Jonathan Polan, an Adjunct Associate Professor from Weill Medical College of Cornell University, has described the emergence of the earliest attachment behaviors of newborn rats. These maternally-directed orienting and proximity-seeking behaviors develop rapidly over the first two days of postnatal life. Funded by an NIMH Research Career Development Award, he is now investigating the roles of early experience in shaping these behaviors and the central nervous system mechanisms involved in controlling them. Extending this work, Drs. Brunelli, Hofer, and Shair are characterizing these earliest forms of attachment behavior in animals selectively bred to express extremes in infant rat separation anxiety.
Dr. Hofer and his group continue their investigation of a novel response to isolation in which an infant pup's ultrasonic vocalizations are greatly intensified following brief interaction with its mother. This potentiated reaction to separation models responses to maternal separation seen in human toddlers. Ongoing work is studying the underlying CNS substrates for this rodent analog to the Ainsworth Strange situation test. At present, pharmacological studies implicate the involvement of the kappa opioid system in this response.
Molecular and Genetic Mechanisms in Brain Development Dr. Barr's research focuses on the neural circuitry that mediates both the therapeutic and adverse effects of opioid peptides and opiate drugs in the young. The goal of this work is to map the neural substrates for opiate-induced analgesia and opiate-induced reward in order to determine how those neural substrates change during normal pre- and postnatal development.
Dr. Wiedenmayer is investigating the molecular and neural processes that underlie developmental changes in responses to stress. He has discovered that the pattern of activation of brain regions that follows exposure to a threatening stimulus changes dramatically with age. He is now studying the neurotransmitters and neuromodulators involved in mediating behavioral responses to stress in the young rat.
Dr. Gingrich is interested in the role of the serotonergic system in the expression of normal and pathological behaviors. He has approached this problem by developing genetically altered ("knockout") mice that lack specific receptors for serotonin. His laboratory recently became the first to create mice lacking the serotonin 2A receptor subtype. These mice are hypothesized to be deficient in some of the circuits established in early life that regulate anxiety and stress in adulthood. Interestingly, these mice also appear to be insensitive to hallucinogenic drugs such as LSD. These models provide important tools for the study of serotonergic and other brain mechanisms involved in the development of anxiety and schizophrenia.
Gene Environment Interactions Clinical evidence shows that genetic predisposition to affective disorders strongly interacts with early attachment experience to create vulnerability to separation anxiety in childhood and to panic disorder and major depression in adulthood. Studies by Drs. Brunelli and Hofer provide the first animal model in which these intertwining influences can be experimentally analyzed and the neurobiological and genetic mechanisms delineated. They have used selective breeding to produce two strains of rats that differ markedly in a juvenile expression of anxiety, the separation cry. Current work focuses on characterizing the neural controls of this vocalization response and changes in other systems that have been co-selected along with rates of vocalization. Together with Dr. Shair, a series of behavioral and physiological tests are being conducted that will reveal the types of anxiety or depressive states that are linked developmentally to the early-selected trait.
The Long-Term Effects of Early Experience A central tenet of Developmental Psychobiology is that experiences of early life have effects lasting into adulthood. Normal and abnormal developmental experiences have been shown to affect adult responses to stress, increase or decrease risks of cardiovascular disease, shape the expression of emotional states, and modulate vulnerability to psychiatric disorders. Drs. Myers and Shair, along with collaborators in the Department of Pediatrics, are using animal models to elucidate mechanisms that account for long-term effects of alterations in the pre- and postnatal environment. A recently funded grant from NICHD is focused on investigating the effects of altered nutrition and specific types of mother/infant behavioral interactions on metabolic and neurobehavioral disorders.
Research Training
The department coordinates an NIMH-funded Research Training Program for postdoctoral fellows. A five-year renewal of this grant, directed by Drs. Hofer and Myers, was awarded for the period July 1998 to June 2003. The 20 faculty members represent five other departments from NYSPI and the Perinatology Division of the Pediatrics department at CPMC. In addition, undergraduate and graduate students and postdoctoral students from many other programs conduct research and receive training in the department.
Future Directions
As of January 2001, the department will
benefit from participation in the newly formed Sackler Institute for Developmental
Psychobiology at Columbia University. The institute and an endowed professorship
were established by a gift from the Sackler Foundation and will foster
interdisciplinary research on developmental processes relevant to the
etiology of psychiatric illness. Dr. Hofer is the first Sackler Professor
and Director of the Institute. Dr. Fifer will be the Assistant Director,
Dr. Myers will direct the subdivision on Animal Models within the Behavioral
Neuroscience Division, and Dr. Polan will be the Liaison Scientist with
the Cornell Sackler Institute. The Institute will have two other divisions,
Basic Sciences directed by Dr. Thomas Jessell of the Department of Biochemistry
and Molecular Biophysics at the medical school, and Clinical Sciences
directed by Dr. Myrna Weissman, Chief of the NYSPI Department of Clinical
Epidemiology.
Dr. Susan Brunelli, with Dr. Myron Hofer, center, and Dr. Michael Myers