Developmental Psychobiology
Michael M. Myers, Ph.D., Chief of Psychiatric Research
Gordon A. Barr, Ph.D., Research Scientist V
Susan A. Brunelli, Ph.D., Research Scientist IV
Myron A. Hofer, M.D., Research Scientist VIII
William P. Fifer, Ph.D., Research Scientist VI
Jay A. Gingrich, M.D./Ph.D., Research Associate
Jonathan Polan, M.D., Research Associate
Harry N. Shair, Ph.D., Research Scientist IV
Christoph P. Wiedenmayer, Ph.D., Research Associate
This department’s research focuses on the processes involved in the development
of behavior and the biological systems that are intertwined with behavior. We
study how naturally occurring experiences interact with genetic mechanisms to
determine behavioral and physiologic traits throughout the life span and how
deviations in these interactions alter normal development. Investigation of
these developmental processes provides important clues about 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. Research in the department is facilitated by a postdoctoral
training grant from the National Institute of Mental Health and by the newly
formed Sackler Institute for Developmental Psychobiology.
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 pursued a program of research on the effects of fetal stimulation and
experiences on brain and behavior development. Recently, Dr. Catherine Monk, a
Sackler Awardee, and Dr. Richard Sloan from the Department of Behavioral
Medicine have joined with Drs. Fifer and Myers to investigate the influence of
maternal emotional state on the fetus. In particular, they are funded to study
associations between maternal depression and anxiety on fetal and infant
development. Drs. Fifer and Myers also incorporate these approaches in a study
of early markers of risk for Developmental Disorders and Sudden Infant Death
(SIDS). This NICHD funded study involves exchange of technology and data between
the sophisticated research environment of New York State Psychiatric Institute
and the high-risk rural populations in the Pine Ridge Reservation in South
Dakota. Extensions of this work with the Department of Pediatrics has uncovered
important new relationships between sleep-state, body position and the
developing nervous system in prematurely born infants. Most recently, together
with colleagues from Environmental Health Science at Columbia, assessments of
sleep dependent physiology are being examined in infants exposed to
environmental toxins during pregnancy.
Mechanisms of Early Attachment and Separation
Dr. Polan, an Adjunct Associate Professor from Weill Medical College of Cornell
University, is investigating the emergence of attachment behaviors exhibited by
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. Working with Dr. Polan, 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.
In related animal studies, Dr. Shair, in collaboration with Drs. Brunelli and
Hofer are investigating a novel response to separation from the mother in which
an infant rat pup’s vocalizations are greatly intensified following brief
interaction with its mother. This potentiated reaction to separation appears
similar to responses of human toddlers when they are separated from their
mothers. Ongoing work is studying the role of early experience in the transfer
of the potentiated response to a secondary attachment figure such as the father.
Molecular and Genetic Mechanisms in Brain Development
Several investigators in the department are pursuing questions relating to the
molecular and genetic mechanisms that govern brain development and how exposure
to drugs and other experiences of early life can alter neurobehavioral traits.
Work in Dr. Barr's laboratory focuses on the neural circuitry that mediates both
the therapeutic and adverse effects of opiate drugs in the young. The goal of
this work is to map the neural substrates for opiate induced analgesia and
reward and for opiate induced tolerance and dependence. In addition, this work
seeks to determine how those neural substrates change during normal pre and
postnatal development. Recently, his laboratory has shown that the ability of
NMDA glutamate antagonists to ameliorate morphine induced tolerance and
withdrawal is totally lacking in the infant. This suggests that putative
therapeutics for the adults may be ineffective in infants. Currently, he and his
colleagues are characterizing developmentally regulated changes in gene
expression induced by morphine withdrawal and dependence.
In another area, Dr. Wiedenmayer is investigating the molecular and neural
processes that underlie developmental changes in responses to aversive stimuli
and threat in young rats. His work is supported by a career development award
from the National Institute of Mental Health. He has discovered that the pattern
of activation of brain regions that follows exposure to an aversive stimulus
changes dramatically with age. In particular, threat induces the expression of
the neuropeptide corticotropin-releasing hormone (CRH) in specific brain areas
in an age-dependent way. He is pursuing the question of whether such
differential CRH expression may underlie the developmental changes in behavioral
and physiological responses to threat.
Finally, Dr. Gingrich's group 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 proteins related to serotoninergic neurotransmission. His laboratory
became the first to create mice lacking the serotonin 2A receptor subtype and
among the first to recognize that mice lacking the serotonin transporter exhibit
paradoxical depression-related behavioral changes. These models provide
important tools for the study of serotonergic and other brain mechanisms
involved in the development of depression and schizophrenia.
Gene Environment Interactions in the Development of Anxiety
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. In addition, Drs.
Brunelli and Shair have teamed with Dr. Myers to investigate the relationship
between early, inherited separation responses and autonomic and cardiovascular
functioning in the selected lines.
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. Within this
context, Drs. Myers, Shair, and Fifer have initiated a program of research
integrating studies in both animal models and human infants to elucidate
mechanisms that account for long-term effects of alterations in the pre- and
postnatal environment. Two recently funded grants from National Institutes of
Child Health and Human Development and Environmental Health Sciences focus on
investigating the effects of altered nutrition and specific types of
mother/infant behavioral interactions during early development on metabolic and
neurobehavioral disorders later in life.
Research Training
The department coordinates an NIMH-funded Research Training Program for
postdoctoral fellows. This program supports the mental health related research
of 5 M.D. and Ph.D. fellows. There are 20 sponsoring faculty members in the
program that represent five other departments from the Psychiatric Institute and
the Perinatology Division of the Pediatrics Department at Columbia. In addition,
the department sponsors the training and research of several undergraduate and
graduate students, as well as postdoctoral students from other departments.
Sackler Institute for Developmental Psychobiology
In April of 2001, The Sackler Institute was incorporated at Columbia and funded
to provide an endowed chair, the Sackler Institute Professorship, a yearly Award
to support young investigator research, research support for faculty, and
construction costs for the new Sackler Institute Laboratories that now house the
Department of Developmental Psychobiology. Dr. Myron Hofer became the first
Sackler Professor and Director of the Institute with Dr. William Fifer as
Assistant Director. The Institute has three divisions: The Clinical Research
Division led by Dr. Myrna Weissman, Chief of the NYSPI department of Clinical
and Genetic Epidemiology, the Behavioral Neuroscience Division led by Drs.
Michael Myers and William Fifer and the Basic Science Research Division led by
Dr. Thomas Jessell of the Center for Neurobiology and Behavior. Other faculty
were appointed: Dr. Bradley Peterson as head of the Developmental Neuroimaging
Laboratory and Dr. Jonathan Polan as Liaison to the Weill-Cornell Sackler
Institute. The first Sackler Award went to Dr. Catherine Monk for her studies of
Fetal Vulnerability to Anxiety and Depression. The Institute also sponsored a
national conference titled, “When the Bough Breaks: Perspectives on Attachment,
Theory, Psychobiology and Implications for Social Policy.” Drs. Hofer, Peterson
and Schechter were speakers, the Panel on Social Policy was moderated by Dr.
Herbert Pardes, and the closing commentary given by Dr. John Oldham. This
conference has become the basis for a forthcoming book edited by Dr. Susan
Coates, Dr. Jane Rosenthal and Dr. Daniel Schechter. Other institute programs
designed to foster interdisciplinary research include the award of small grants
to postdoctoral fellows and support of visiting developmental scientists.