| ARCHIVE
ANNUAL
REPORT
April 27, 2001 - June 30, 2002
SACKLER INSTITUTE FOR DEVELOPMENTAL PSYCHOBIOLOGY
AT COLUMBIA UNIVERSITY
The Sackler Institute and Professorship were funded at Columbia
in December 2000 by a gift from the Sackler Foundation and
formally established by act of the Columbia University Faculty
Senate on April 27th 2001. This report covers the first full
year of operations through the end of the fiscal year, June
30, 2002. The Sackler Award program, established in 1998,
became a part of the Sackler Institute at the time of its
founding.
The
structure and faculty of the Institute during this first year
were as follows:
Director,
Dr. Myron A. Hofer
Assistant Director, Dr. William P. Fifer
Chief, Basic Science Division - Dr. Thomas Jessell
Chiefs, Behavioral Neuroscience Division - Drs. Michael Myers
and William Fifer
Chief, Clinical Division - Dr. Myrna Weissman
Head, Developmental Neuroimaging Laboratory - Dr. Bradley
Peterson
Liason, Cornell - Sackler Institute - Dr. Jonathan Polan
Sackler Awardees: 2000-2001, Dr. Catherine Monk
2002-2003, Drs. Joshua Gordon and Cheryl Corcoran
Construction of the Sackler Laboratories moved forward swiftly
and was completed in October 2001. The New York State Psychiatric
Institute Department of Developmental Psychobiology moved
into the offices and laboratories in November and a tour of
the space took place after the first meeting of the Internal
Advisory Committee on November 28th, 2001. Dr. Mortimer Sackler
visited the new laboratories and met informally with the faculty
on January 22, 2002. The offices, laboratories and conference
room are working out extremely well and the Sackler faculty
that have moved into the laboratories are delighted with them.
This space has already become an important geographic center
for the Institute's activities at the medical center.
Faculty
and Sackler Awardees
A new faculty member was appointed as a Sackler Scientist
in July of 2001. Dr. Bradley Peterson was recruited from Yale,
and heads up the new Developmental Neuroimaging Laboratory
in the Institute. Dr. Peterson has an international reputation
in functional magnetic imaging of childhood psychiatric disorders
and leads a multi-site study collecting serial MRI data on
a large cohort of several hundred children from the neonatal
period forward. Dr. Peterson's research is further described
in the Faculty Research section that follows.
Dr.
Thomas Jessell, was awarded the 13th Annual Bristol Myers
Squibb Award for distinguished achievement in neuroscience
in September 2001.
The
first Sackler Awardee, Dr. Catherine Monk, was awarded a 5
year Research Scientist Development Award from NIMH to continue
her research on fetal origins of vulnerability to anxiety
and depression and the role of maternal to fetal transmission
of physiological signs of anxiety. Clearly the Sackler Award
played a crucial role in her career, making the highly competitive
grant possible. Dr. Monk's report on her Sackler Award research
is included as the final section of this report.
The timely award of federal funding to Dr. Monk opened the
Sackler Award Program to new applicants. We received 7 excellent
applications and deciding between them was extremely difficult.
In the end, the Award Committee decided to fund two of the
applicants by extending the start date 2 months and using
the remainder of the funds made available as a result of Dr.
Monks' federal grant award.
Dr. Joshua Gordon will be studying the novel early developmental
effects of an inducible, region-specific gene knockout of
the serotonin 1A receptor. This new advance in molecular genetic
technique allows the investigator to control expression of
the targeted gene, turning it on or off at any desired developmental
stage. Dr. Gordon's neurophysiological studies will be done
in the Department of Neurobiology and Behavior as well as
the Department of Psychiatry.
Dr. Cheryl Corcoran's project involves the prospective study
of how Schizophrenia is triggered in an unusual population
of adolescents at very high risk (50% in 5years) due to prodromal
symptoms and/or a very strong family history. Salivary cortisol
has been found to be a novel predictor in Dr. Corcoran's preliminary
work.
Sackler Fellows
Through the Columbia contribution to the Institute, we were
able to appoint 3 Sackler fellows, two of whom received $5,000.00
mini-grants (Drs. Schechter and Feder) and one is being supported
by our NIMH funded Research Training Program (Dr. Inge-Marie
Eigsti). Dr. Schechter, working with Drs. Hofer and Myers,
has been studying the intergenerational transmission of trauma
in high risk populations of mothers with past histories of
abuse, and their infants. Dr. Schechter has been invited to
present his findings at the World Association for Mental Health,
the American Psychiatric Association and the International
Society of Traumatic Stress. Dr. Feder has been working with
Dr. Weissman studying the familial transmission of depression
across 3 generations, searching for markers of latent genetic
risk using quantitative EEG and startle response measures.
Dr. Eigsti is the first joint Columbia-Cornell Sackler Institute
Fellow and will be studying the deployment of attention in
autistic and normal children using novel perceptual tests
and concurrent neuro-imaging. She will be working with Dr.
Fifer here at Columbia and Dr. Casey at Cornell.
Interdisciplinary Conferences
Other activities included our joint sponsorship, with the
Parent-Infant Program of the Columbia Psychoanalytic Institute,
of a National Conference on November 3rd 2001 with the title
" When the Bough Breaks: Attachment Theory, Psychobiology
and Social Policy". Drs. Myron Hofer, Bradley Peterson
and Daniel Schechter were among the speakers as well as Dr.
Susan Coates of the Columbia Parent - Infant Program. The
meeting plans were modified after September 11th to include
Dr. Robert Pynoos, an authority on Childhood Traumatic Stress
and a panel discussion on Public Policy chaired by Dr. Herbert
Pardes. The conference was well attended and generated a great
deal of subsequent interest, resulting in a book contract
with the Analytic Press. Drs. Coates and Schechter are editing
this book which will be the first major publication of the
Sackler-funded Parent - Infant Program and the Sackler Institute
at Columbia.
The Institute also sponsored two interdisciplinary symposia
at international meetings: one on Autism at the annual meeting
of the International Society for Developmental Psychobiology
and the other on Early Learning and Attention at the Annual
Winter Conference of Developmental Science. In addition, three
visiting scientists were sponsored to come to Columbia to
meet with Sackler Scientists to share their expertise in new
research methods and approaches in the areas of: early cortisol
regulation, visual motor development and infant eye blink
conditioning - animal and human.
The Columbia Parent - Infant Program, established through
funding from the Sackler Award in the years 1999-2000, sponsored
a symposium at the 8th Congress World Association for Infant
Mental Health Conference in Amsterdam this summer. This was
very well received and in his discussion of Dr. Schechter's
paper (see Sackler Fellows above) Dr. Peter Fonagy, one of
the leading figures in this field, gave this assessment:
"The Columbia PIP group has arrived at that elusive Holy
Grail of infant
mental health work, the deep and genuine integration of research,
theory and clinical practice. There are but a handful of groups
around the world that can lay claim to such an achievement.
It is indeed a privilege to discuss this work and underscore
for you the coherence and sophistication which reflects the
integration of research and practice based on solid theoretical
foundations."
Our plans for next year include a workshop
series here at Columbia on Experimental Mutant Mice and on
Gene Protein Chip Technology as well as a major conference
on New Findings in Developmental Effects of Maternal Smoking.
Faculty Research
Brief reports on the research of each of the 7 Sackler Scientists
over the past year are given in alphabetical order below.
Their research, taken together, spans the full interdisciplinary
range from clinical epidemiology to molecular genetics, as
is presented below. Following this narrative, a listing of
the publications over the past year and the active grant support
of each scientist is given, again in alphabetical order. A
report on the research of Sackler Awardee, Dr. Catherine Monk
makes up the final section of this report.
1. Human Fetal Behavior and Intrauterine Influences on Vulnerability
to Psychiatric Illness - Dr. William Fifer
The general research program has focused on the effects of
the early environment on fetal and infant brain/behavior development.
Our most recent efforts have focused on the effects of prenatal
risk factors including, maternal nicotine and alcohol use
during pregnancy, as well as maternal stress and anxiety,
on autonomic nervous system development. With Dr. Monk, a
former Sackler Fellow, and Dr. Sloan from the Department of
Behavioral Medicine, we have expanded the research to include
the influence of maternal depression and anxiety on fetal
and infant development. Also with Dr. Myers we continue to
study early markers of risk for Developmental Disorders and
Sudden Infant Death (SIDS). This NICHD funded study involves
a mutually beneficial technology exchange between New York
State Psychiatric Institute and the high-risk populations
in Washington Heights and on the Pine Ridge Reservation in
South Dakota. A further extension of this work, with the Department
of Pediatrics, focuses on the developing nervous system in
prematurely born infants and, together with colleagues from
the Division of Environmental Health Science at Columbia,
assessments of sleep dependent physiology in infants exposed
to environmental toxins during pregnancy.
During this past year we have also initiated three new studies
in active
collaboration with colleagues from the Sackler Institute at
Cornell. With B.J.
Casey we have designed a study to investigate the relationship
between markers
of autonomic nervous system regulation in the perinatal period
with attentional
regulation in older children. Inge-Marie Eigsti has begun
work on a study of brain
activation and low-level issues of attention and learning
in newborn human
infants using an eye blink conditioning paradigm, and with
Bruce McCandliss, we
are exploring the use of high density EEG technology to investigate
the ontogeny
of event related potentials in very young infants.
2. Biological Mechanisms in Early Separation Anxiety - Dr.
Myron Hofer
Recent research with Drs. Susan Brunelli and Harry Shair has
focused on early separation anxiety employing a novel developmental
- genetic approach: selective breeding for high and low levels
of separation calling in infant rats. This is the first study
ever conducted on selective breeding for an infantile trait
in a mammal, and raises the fascinating question of how continued
selection can affect the developmental trajectory of the trait
over time, both before and after the age at which selection
is carried out. Since natural selection is known to act on
infantile traits, this study brings evolution and its effects
on development into the realm of laboratory study. Furthermore,
it allows us to study the brain mechanisms responsible for
extreme high and low levels of this first anxiety behavior,
mechanisms that we and others have shown are very similar
to those acted upon by known anxiolytic drugs and experimental
anxiogenic compounds previously studied in humans. A recent
publication, provided in the next section, describes some
of the interesting questions raised by this study and the
answers we are beginning to get from the data generated.
My other interest is in the theory of development and the
implications of our work for new conceptualizations of attachment,
separation anxiety and the long term developmental effects
of different parenting patterns on adult vulnerability to
psychiatric illness. Several of my papers on these subjects
published in the past year are listed in the publicatons section.
3. Molecular Genetic Specifications of Developing Neuronal
Circuitry
- Dr. Thomas Jessell
Our work has addressed the mechanisms that control the assembly
of neural circuits in the vertebrate central nervous system.
These studies have explored the link between neuronal identity
and circuitry: how does the early specification of neuronal
identity define the position of neurons, the projection pattern
of their axons, and the selectivity of their synaptic contacts?
We have focused on neurons that form the monosynaptic stretch
reflex circuit in the spinal cord, for two reasons. First,
this circuit forms early in development, in an activity-independent
manner, suggesting that its assembly is genetically encoded.
Second, a century of anatomy and physiology, from the pioneering
studies of Sherrington and Ramón y Cajal onward, has
provided a rigorous cellular and functional framework for
interpreting molecular steps in the assembly sensory-motor
connections. Over the past year we have addressed molecular
basis of motor neuron projections into the periphery, and
the central connections between proprioceptive sensory neurons
and motor neurons.
4. Early Nutritional Influences on Vulnerability to Disease
- Dr. Michael Myers
For the past several years, there has been renewed interest
in the effects of inadequate nutrition during pregnancy, undergrowth
of the fetus, and vulnerability to disease later in life.
From large epidemiological studies, it appears that cardiovascular
disease, diabetes, schizophrenia, and depression all share
the common trait of being influenced by disturbances during
this critical period of development. While long-term effects
of early experiences has been a focus of much research within
the field of Developmental Psychobiology, the proximal mechanisms
and chain of events that account for enduring changes in disease
vulnerability remain largely undiscovered. This has been a
ongoing focus of work in my laboratory. This year, in collaboration
with Drs. William Fifer and Harry Shair in our department,
Dr. Robert Vosatka in Pediatrics at Columbia, and Drs. Morris
Cohen and David Brown at Newark Beth Israel Hospital, we obtained
a new five year NIH grant for over $2,000,000 to pursue this
work in both animal models and human infants.
These new studies will focus on effects of variation in nutrient
availability in the perinatal period on physiological, biochemical
and behavioral characteristics of newborn infants. Indices
derived from animal studies will be incorporated into human
studies, and the underpinnings of correlative findings from
human studies will be pursued in animal models. The studies
will determine if human infants with low birth weights, or
rats whose mothers were underfed during pregnancy, express
differences in cardiovascular and behavioral responses to
feeding and postural challenge. In addition, we are pursuing
the hypothesis that alterations in methylation of regulatory
regions of certain genes are key to understanding the permanent
changes in gene expression that underlying the early effects
of variation in growth.
5. Neuroimaging in Children At Risk - Dr. Bradley Peterson
The developmental neuroimaging laboratory successfully moved
from Yale University to Columbia and the Psychiatric Institute.
Key staff were retained and new staff were hired, including
an Assistant Professor who is a skilled electrical engineer
with a specialty in MRI signal processing.
Imaging
studies of impulse control in normal and ill children and
adults have continued. Scanning is still performed at Yale,
and we hope to transition to scanning on a new scanner at
the Psychiatric Institute that is scheduled for operation
in the spring of 2003.
New
collaborative research has begun with established investigators
at Columbia. Most notably, anatomical and functional imaging
studies have begun on a large, 3-generational cohort followed
by Dr. Myrna Weissman over the past 20 years. Individuals
in the 2nd and 3rd generation who are at either high or low
risk for major depressive illness are being studied with MRI
and with neuropsychological tasks designed to test the integrity
of neural systems thought to be dysfunctional in depression.
An R01 was submitted in the spring of 2002 to fund this study.
Imaging studies of autistic spectrum disorder have begun in
collaboration with Dr. Marc Patterson, Chief of Pediatric
Neurology at Columbia, Dr. Agnes Whitaker, Director of the
Neuropsychiatry Clinic, and Dr. Ian Lipkin, Director of the
Center for Immunopathogenesis and Infectious Diseases at Columbia.
6. Origins of the First Infant Attachment - Dr. Jonathan Polan
We have been studying the transformation of the newborn's
first undirected movements into fully competent maternally-directed
behaviors -- orienting behaviors by which the infant mammal
achieves and maintains contact with its mother. We have discovered,
to our surprise, that whereas newborn rat pups perform spontaneous
and reflex orienting behaviors equally often with or without
the mother, in the first hours after birth, over the next
two days they come to reserve them exclusively for encounters
with the mother’s specific features. In the same period,
infants develop the first evidence of motivation: performing
these behaviors more intensely after a period of her absence.
Together, specificity for maternal features and maternal deprivation-induced
enhancement equip the newborn rat with a robust preference
for interaction with its mother, and are core attributes of
an “attachment” to her. These behaviors, initially
performed with little relation to each other, develop surprisingly
rapidly into organized patterns and become functionally linked
with the better known behaviors of suckling.
We are currently exploring three developmental questions raised
by these early behavioral events: 1) What behavioral processes
are responsible for such rapid development of deprivation-induced
enhancement of maternally-directed orienting behaviors? 2)
What processes of learning about the mother contribute to
the newborn’s orienting behaviors gaining specificity
for her features? 3) What behavioral mechanisms relate maternally-directed
orienting behaviors to the nipple grasp and suckling?
7. Clinical and Epidemiological Studies of Genetic Risk and
Biological Markers in the Development of Affective Disorders
- Dr. Myrna Weissman
Myrna Weissman, Ph.D., Virginia Warner, M.P.H., and Priya
Wickramaratne, Ph.D. are completing data collection on a three
generation longitudinal study of depressed grandparents, their
offspring and grandchildren. The study includes diagnostic
and neuropsychological assessment across the generation. In
collaboration with Bradley Peterson, M.D., an NIMH grant has
been submitted to conduct fMRI studies in the second and third
generation. We've just learned that this study received a
favorable review and will be funded.
Myrna Weissman, Ph.D. and Dan Pilowsky, M.D. have initiated
a 6 site study funded by NIMH to determine the impact of treating
maternal depression on the children’s symptoms and functioning.
Also, directly related to the Sackler Institute: Sanjay Mathew,
M.D., Postdoctral Fellow, received an American Foundation
for Suicide Prevention Young Investigator Award to conduct
neuroimaging studies of brain structure in suicidal and non-suicidal
depressed adolescents grown-up. Adriana Feder, M.D., Assistant
Professor, received a NARSAD Junior Investigator Award for
her project "The Neurobiology of Prepubertal Onset Depression"
and is completing the data collection on the psychopathology
in offspring of depressed mothers coming to primary care.
Yoko Nomura, Ph.D., Research Associate, developed and submitted
a study examining the psychosocial and biomedical causes and
sequelae associated with perinatal risk, such as low birth
weight and pre-term birth.
Faculty Publications (2001-2002)
WILLIAM FIFER
Fifer,W.P. and Myers, M.M. Sudden fetal and infant deaths:
shared characteristics and distinctive features. Seminars
in Perinatology, 26(1):89-96,2002.
Monk,
C., Fifer, W.P., Sloan, R.P, Myers, M.M., Bagiella, E., Ellman,
L. and Hurtado, A. Physiologic responses to cognitive challenge
during pregnancy: Effects of task and repeat testing. International
Journal of Psychophysiology, 40(2):149-159, 2001.
Fifer, W.P., Monk, C. and Grose-Fifer, J. Prenatal development
& risk. In G.
Bremner and A. Fogel (Eds). Blackwell Handbook of Infancy
Research, Oxford,
UK: Blackwell Publishers Ltd., 505-542, 2001.
MYRON HOFER
Hofer, M.A., Brunelli, S.A. and Shair, H.S. Developmental
effects of selective breeding for an infantile trait: the
rat pups ultrasonic isolation call (USV). Develop. Psychobiol.
39, 1-16, 2001.
Brunelli,
S.A., Hofer, M.A. and Weller, A. Selective breeding for infant
vocal response: role for postnatal maternal effects? Develop.
Psychobiol. 38:221-228,2001.
Hofer,
M.A. and Sullivan, R.M. Toward A Neurobiology of Attachment.
In Nelson, C.A. and Luciana, M. (Eds.) Handbook of Developmental
Cognitive Neuroscience, MIT Press, Boston, 599-616, 2001.
Hofer,
M.A., Shair, H.S. and Brunelli, S.A. Ultrasonic vocalization
in rat and mouse pups in Current Protocols in Neuroscience,
8.14.1 to 8.14.16, 2001.
Hofer,
M.A. Origins of Attachment and Regulators of Development within
Early Social Interactions: From Animal to Human. In Kalverboer,
A.F. and Gramsbergen, A. (Eds) Handbook of Brain and Behaviour
in Human Development, Kluwer Academic Publishers, Great Britain,
821-840, 2001
Hofer, M.A. Evolutionary concepts of anxiety. In Stein D.J.
and Hollander, E. (Eds.) Textbook of Anxiety Disorders, Am.
Psychiatric Press, Washington, 65-78, 2002.
THOMAS JESSELL
Pierani, A. L. Moran-Rivard, M.J. Sunshine, D.R. Littman,
M. Goulding, and T.M. Jessell (2001). Control of interneuron
fate in the developing spinal cord by the progenitor homeodomain
protein Dbx1. Neuron. 29, 367-384.
Muhr, J., Andersson, E., Persson, M., Jessell, T.M. and Ericson,
J. (2001). Groucho-mediated transcriptional repression establishes
progenitor cell pattern and neuronal fate in the ventral neural
tube. Cell, 104, 861-873.
Wilson, S.I., Rydstrom, A., Trimborn, T., Willert, K., Nusse,
R., Jessell, T.M., Edlund, T. (2001). The status of Wnt signaling
regulates neural and epidermal fates in the chick embryo.
Nature, 411, 325-330.
Briscoe, J., Chen, Y., Jessell, T.M. and Struhl, G. (2001).
A hedgehog-insensitive form of patched provides evidence for
direct long-range patterning activity of Sonic hedgehog in
the neural tube. Molecular Cell 7, 1279-1291.
Srinivas S, Watanabe T, Lin CS, William CM, Tanabe Y, Jessell
TM, and Costantini F. (2001). Cre reporter strains produced
by targeted insertion of EYFP and ECFP into the ROSA26 locus.
BMC Dev Biol. 2001;1:4.
Yang, X, Arber, S., William, C., Li, L., Tanabe, Y., Jessell,
T.M., Birchmeier, C., and Burden, S.T. (2001) Patterning of
Muscle Acetylcholine Receptor Gene Expression in the Absence
of Motor Innervation. Neuron, 30, 399-410.
Novitch, B.G., Chen, A.I., and Jessell, T.M. (2001). Coordinate
regulation of motor neuron subtype identity and pan-neuronal
properties by the bHLH repressor Olig2. Neuron, 31, 773-789.
Vallstedt, A., Muhr, J., Pattyn, A., Pierani, A., Mendelsohn,
M., Sander, M., Jessell, T., and Ericson, J. (2001). Different
levels of repressor activity assign redundant and specific
roles to Nkx6 genes during motor neuron and interneuron specification.
Neuron, 31, 743-755.
Liu, J.P., Laufer, E. and Jessell, T.M. (2001). Assigning
the positional identity of spinal motor neurons: rostrocaudal
patterning of Hox-c protein expression by FGFs, Gdf11 and
Retinoids. Neuron, 32, 997-1012.
Price, S.R., De Marco Garcia, N.V. Ranscht, B. and Jessell,
T.M. (2002). Regulation of motor neuron pool sorting by differential
expression of type II cadherins. Cell, 109, 215-216.
Muller, T., Brohmann, H., Pierani, A., Heppenstall, P.A.,
Lewin, G.R., Jessell, T.M., and Birchmeier, C. (2002) The
homeodomain factor Lbx1 defines two programs of dorsal horn
neuron differentiation. Neuron, 34, 551-562.
Pun, S., Sigrist, M., Santos, A.F., Rüegg, Sanes, J.R.,
Jessell, T.M., Arber, S., and Caroni, P. (2002). An intrinsic
distinction in neuromuscular junction assembly and maintenance
in different skeletal mucles. Neuron, 34, 357-370.
Nordström, U., Jessell, T.M., and Edlund, T. (2002).
Progressive induction of caudal neural character by graded
Wnt signaling. Nature Neuroscience, 5, 525-532.
Livet, J., Sigrist, M., Stroebel, S., Price, S.R., Henderson,
C.E., Jessell, T.M, and Arber S. (2002). ETS gene Pea3 regulates
motor neuron position and axonal branching. Neuron, 35, 877-892.
Wichterle, H., Lieberam, I., Porter, J., and Jessell, T.M.
(2002). Directed differentiation of embryonic stem cells into
motor neurons. Cell, 110, 385-397.
MICHAEL MYERS
Cohen, M, Brown, DR and Myers MM. Cardiovascular responses
to pacifier experience and feeding in newborn infants. Developmental
Psychobiology, 39: 34-39, 2001.
Sloan,
RP, Bagiella E, Shapiro PA, Kuhl JP, Chernikhova D, Berg J
and Myers MM. Hostility, gender, and cardiac control. Pyschosomatic
Medicine, 63: 434-440.
Monk
C, Fifer WP, Sloan RP, Myers, MM, Bagiella E, Ellman L, and
Hurtado A. Physiologic responses to cognitive challenge during
pregnancy: effect of task and repeated testing. International
Journal of Psychophysiology, 40: 149-159, 2001.
Fifer WP and Myers, MM. Sudden fetal and infant deaths: shared
characteristics and distinctive features. Seminars in Perinatology,
26: 89-96, 2002.
BRADLEY PETERSON
Peterson BS, Ment LR. The study of preterm birth and developmental
brain abnormalities. Trends Neurosci, 24: 131-132, 2001.
Peterson
BS, Ment LR. The necessity and difficulty of conducting MRI
studies on infant brain development. Pediatrics, 107:593-594,
2001.
Peterson
BS, Feineigle PA, Staib LH, Gore JC. Automated measurement
of latent morphological features of the human corpus callosum.
Hum Brain Mapping, 12:232-245, 2001.
Anderson
AW, Colson ER, Marois R, Peterson BS, Duncan CC, Ehrenkranz
RA, Konstantino M, Sarofin H, Schneider KC, Gore JC, Ment
LR. Neonatal auditory activation detected by functional magnetic
resonance imaging. Magnet Reson Imaging, 19:1-5, 2001.
Peterson
BS, Staib L, Scahill L, Zhang H, Anderson C, Leckman JF, King
R, Gore JC, Cohen DJ, Albert J, Webster R. Regional brain
and ventricular volumes in Tourette syndrome. Arch Gen Psychiatry,
58:427-440, 2001.
Jeong
J, Gore JC, Peterson BS. Mutual information analysis of the
EEG in patients with Alzheimer's disease. Clin Neurophys,
112: 827-835, 2001.
Peterson
BS, Pine DS, Cohen P, Brook J. A prospective, longitudinal
study of tic, obsessive-compulsive, and attention deficit-hyperactivity
disorders in an epidemiological sample. J Amer Acad Child
Adolesc Psychiatry, 40: 685-695, 2001.
Morshed
SA, Parveen S, Leckman JF, Mercadante MT, Bittencourt-Kiss
MH, Miguel EC, Yazgan Y, Fujii T, Paul S, Peterson BS, Zhang
H, King RA, Scahill L, Lombroso PJ. Antibodies against striatal,
nuclear, cytoskeletal and streptococcal epitopes in children
and adults with Tourette’s syndrome, Sydenham’s
chorea, and autoimmune disorders. Biol Psychiatry, 50: 566-578,
2001.
Patwardhan
AJ, Eliez S, Warsofsky IS, Glover GH, White CD, Giedd JN,
Peterson BS, Rojas DC, Reiss AL. Effects of image orientation
on the comparability of pediatric brain volumes using three-dimensional
MR data.
J Comp Assist Tomogr 25:452-7, 2001.
Peterson
BS, Kane M, Alexander GM, Lacadie C, Skudlarski P, Leung H-C,
May J, Gore JC. An event-related functional MRI study comparing
interference effects in the Simon and Stroop tasks. Cognitive
Brain Res,13:427-440, 2002.
Alexander
GM, Packard M, Peterson BS. Sex and spatial position effects
on object location memory following intentional learning of
object identities. Neuropsychologia, 40:1516-1522, 2002.
Alexander
GM, Altemus M, Peterson BS, Wexler B. Replication of a premenstrual
decrease in right-ear advantage on language-related dichotic
listening tests of cerebral laterality. Neuropsychologia,
40:1293-1299, 2002.
Taylor
JR, Morshed SA, Parveen S, Mercadante M, Scahill L, Peterson
BS, King, RA, Leckman JF, Lombroso PJ. An animal model of
Tourette’s syndrome. Am J Psychiatry 159:657-660, 2002.
Jeong
J, Gore JC, Peterson BS. Detecting determinism in a short
time series, with an application to the analysis of stationary
EEG data. Biol Cybernetics,86:335-342, 2002.
Hampson M, Peterson BS, Skudlarski P, Gatenby C, Gore JC.
Detection of functional connectivity using temporal correlations
in MR images. Hum Brain Map, 15:247-262, 2002.
JONATHAN POLAN
Polan, H.J., Milano, D., Eljuga, L., & Hofer, M.A. 2002.
Development of rats' maternally-directed orienting from birth
to day 2. Developmental Psychobiology, 40:81-103.
Polan,
H. J., Eljuga, L., Sacks, T., & Hofer, M.A. 2002. Deprivation
regulates nipple grasp by P2-3 rat pups in a naturalistic
paradigm (abs). Developmental Psychobiology, 41:89.
Eljuga, L., Mathew, E., Hofer, M. A., & Polan, H. J. 2002.
Evidence that newborns’ differential responding to maternal
cues depends on the first day’s experience (abs). Developmental
Psychobiology, 41:76.
MYRNA WEISSMAN
Nomura Y, Warner V, Wickramaratne P. Parents Concordant for
Major Depressive Disorder and the Effect of Psychopathology
in Offspring. Psychol Med 2001; 31: 1211-1222.
Ritsher JEB, Warner V, Johnson JG, Dohrenwend B. Inter-generational
longitudinal study of social class and depression: A test
of social causation and social selection models. Brit J Psychiatry
2001; 178: S84-S90.
Weissman MM, Olfson M, Gameroff M, Feder A, Fuentes M: A Comparison
of Three Scales for Assessing Social Functioning in Primary
Care. Am J Psychiatry 158:460-466, 2001.
Feder A, Olfson M, Gameroff M, Fuentes M, Weissman MM: Medically
Unexplained Symptoms in an Urban General Medicine Practice.
Psychosomatics 42:261-268, 2001.
Goodwin R, Olfson M, Feder A, Fuentes M, Pilowsky D, Weissman
MM: Panic and Suicidal Ideation in Primary Care. Depression
and Anxiety 14:244-246, 2001.
Nomura Y, Wickramaratne P, Warner V, Mufson L, Weissman MM.
Family Discord, Parental Depression and Psychopathology in
Offspring: 10 - Year Follow - up. J Acad Child Adolesc Psychiatry
2002; 41(4): 402-409.
Weissman MM. Juvenile onset major depression includes childhood
& adolescent onset depression and may be heterogeneous.
Arch Gen Psychiatry 2002, 59(3): 223-234.
Gross R, Olfson M, Gameroff M, Shea S, Feder A, Lantigua R,
Weissman MM: Borderline Personality Disorder in Primary Care.
Archives of Internal Medicine 162:53-60, 2002.
Faculty - Active Grant Support
William Fifer
“Perinatal Assessment of At-Risk Infants”
Principal Investigator: Fifer, William P. Role: PI (50%)
$398,920 (current year total)
Agency: NICHD Type: R01 (HD 32774) Period: 05/01/99 - 04/30/04
Goals: These studies focus on making cardiorespiratory measurements
in groups of human fetuses and newborns who are at risk for
developing subsequent neurologic damage and/or Sudden Infant
Death Syndrome.
"Fetal
Responses to Hypoxia During Development"
Principal Investigator: Stark, Raymond I. Role: Project (8%)
$780,000 (current year total)
Agency NICHD Type 5p50 (HD 13063) Period: 07/01/05
Goals: To conduct basic physiologic, endocrine, and behavioral
studies using human premature infants, fetal baboons, and
rats to determine responses to and detrimental effects of
hypoxia, nutritional variation and nicotine during the perinatal
period.
“Fetal
Origins of Disease: Markers, Modulators, Mechanisms”
Principal Investigator: Myers, Michael M. Role: Co-Investigator
(5%)
$385,964 (current year total)
Agency: NICHD Type: RO1 (HD41326) Period: 08/01/01-06/31/06
Goals: These are animal and human infant studies that focus
on cardiovascular and gene expression consequences of variations
in early life growth and nutrition.
2R13MH
HD58769-03 (Fifer, W.P.) 10/01/00-9/30/05
NIMH
International Society for Developmental Psychobiology Student
Travel Grant
R01 HD41326 (Myers, M.M.) 08/01/01-07/31/06
NICHD
Animal and human infant studies to investigate effects of
early diets and growth on subsequent cardiovascular function.
2R01
ES08977 (Perera, F.P.) 04/01/02-03/31/07
NIEHS
Environmental Health in a Cohort of Minority Women/Infants
To investigate the impact of pre- and post-natal exposures
to air pollutants on fetal growth and early childhood neurobehavioral
development.
Primary
Mentor on Dianne grant Catherine Grant
Pending Rauh, CEM clinical trials, Towey grant ( co-investigator?)
Myron Hofer
5T32 MH18264 7/1/98 – 6/30/03
NIMH $165,661/year
Research Training – Psychobiological Sciences
Role: Co-Director
This
grant provides stipends and associated costs for this post
doctoral research
training program.
K-5 MH38632 12/31/97 – 1/1/03
NIMH $100,125/year
The Developmental Effects of Early Maternal Separation
Research Scientist Award to M.A. Hofer. Salary for research
(see below) and training roles.
5RO1
MH40430 12/1/96 – 11/30/02
NIMH $176,442/year
The Developmental Effects of Early Maternal Separation
Role: P.I.
To study how the development of an early emotional trait is
organized and regulated
Thomas Jessell
Howard
Hughes Medical Institute 9/01/02 - 8/31/03 $496,751 (operating
expenses)
Molecular
Analysis of Vertebrate Neural Development
Research support from HHMI is focused on the inductive interactions
that control neural identity in the spinal cord.
RO1
NS33245 09/24/02-08/31/05
NIH $200,000
Control of Motor Neuron Differentiation
To study the mechanisms by which the diversity of different
motor neuron subpopulation are generated.
1P50
MH50733
NIH/NIMH (E. Kandel, M.D.) 09/20/94 - 08/31/04 $124,552-Project
1 (Jessell)
Center
for Neuroscience Research: Genetic Approaches to Neural Plasticity
and Learning
Project 1: The Development of Neural Circuits for a Simple
Reflex Behavior: Genetic Analysis of Motor Neuron Identity
This project aims to define the mechanisms whereby distinct
classes of motor neurons and interneurons are generated and
assembled into functional motor circuits in the spinal cord.
5 P01 CA23767-19 (Competing Renewal)
NIH (Richard Axel, M.D.) 12/1/78 – 07/31/03
$117,443 – Project IV (Jessell)
Proto-Oncogenes: Signaling in Development and Neoplasia
Project IV: Cell Interactions in Motor Neuron Differentiation
The aim of this project will be to focus on the control of
motor neuron diversity in the lateral motor column (LMC),
a class of motor neurons that innervates target muscles in
the limb.
The G. Harold and Leila Y.
Mathers Charitable Foundation
(E. Kandel, M.D.) 9/1/01-08/31/04
$175,000 – Project- Jessell
Molecular Approaches to cognition: The Development and Modification
of Internal Representations within the Brain.
The aim of this project is to determine how individual genes
contribute to the cellular properties essential for the development
and maintenance of cognitive maps.
WELLT066790-C-02-Z
The Welcome Trust 05-01-02-04/30/07
$123.115
Functional Genomics of Neuronal Identity
The aim of this project is to define the molecular cascades
and gene networks involved in the determination of two defined
neuronal cell types – the motor neuron and the olfactory
neuron.
RGP0161/2001
Human Frontier Science Program 4/01/02-03/1/05
$50,000
Functional Analysis of Genetically Defined Interneurons in
the Ventral Spinal Cord
The aim of this project is to develop a genetic basis for
neuronal classification in the spinal cord.
Project
ALS 1/21/02-NA
$100,000
Regulated Gene Expression in Motor Neurons and Neuron Progenitor
Cells.
The aim of this proposal is to apply contemporary methods
of gene manipulation in the mouse to the study of the origins
of ALS and to the design of novel strategies to prevent the
death of motor neurons that occurs in ALS and other neurodegenerative
disorders.
Michael Myers
“Fetal
Origins of Disease: Markers, Modulators, Mechanisms”
Principal Investigator: Myers, Michael M. Role: PI (25%)
$385,964 (current year total)
Agency: NICHD Type: RO1 (HD41326) Period: 08/01/01-06/31/06
Goals: These are animal and human infant studies that focus
on cardiovascular and gene expression consequences of variations
in early life growth and nutrition.
“Perinatal
Assessment of At-Risk Infants”
Principal Investigator: Fifer, William P. Role: Co-Investigator
(25%)
$398,920 (current year total)
Agency: NICHD Type: R01 (HD 32774) Period: 05/01/99 -04/30/04
Goals: These studies focus on making cardiorespiratory measurements
in groups of human fetuses and newborns who are at risk for
developing subsequent neurologic damage and/or Sudden Infant
Death Syndrome.
"Fetal
Responses to Hypoxia During Development"
Principal Investigator: Stark, Raymond I. Role: Co-Director
and
Project Co-Investigator (20%)
$780,000 (current year total)
Agency NICHD Type 5p50 (HD 13063) Period: 07/01/05
Goals: To conduct basic physiologic, endocrine, and behavioral
studies using human premature infants, fetal baboons, and
rats to determine responses to and detrimental effects of
hypoxia, nutritional variation and nicotine during the perinatal
period.
“Hostility
Reduction and Autonomic Control of the Heart”
Principal Investigator: Sloan, Richard P. Role: Co-Investigator
(10%)
$398,710 (current year total)
Agency: NHLBI Type: R01 (HL 63872) Period: 07/01/00 - 06/30/05
Goals: To determine effects of hostility reduction therapy
on psychophysiological reactivity in hostility subjects.
Bradley Peterson
1999
NIMH RO1 MH59139R01 FMRI of Impulse Control in Childhood Disorders
(B. Peterson, PI)
30% Concurrent Effort. To study the neural basis of impulse
control and its dysfunction in childhood neuropsychiatric
disorders.
7/1/99-6/30/03 $2,448,553
2000
NIH/NINDS R01 NS27116-09 Randomized Indomethacin GMH/IVH Prevention
Trial (L.Ment, PI) To test the hypothesis that the administration
of indomethacin protects against long-term structural and
functional abnormalities of the developing brain.
20% Concurrent Effort. Dr. Peterson is directing the functional
and anatomical MRI components of this project
01/01/00-12/31/04 $5,090,855
2001
Tourette Syndrome Association Neuroimaging Studies of the
Amygdala and Hippocampus in TS (B. Peterson, PI) To test the
hypothesis that the volumes of amygdala and hippocampus are
reduced in individuals who have Tourette syndrome
10% Effort.
7/1/01-6/30/02 $75,000
2001
NIMH R01 Subtyping Schizophrenia with Memory Tests, MRI, and
fMRI (B. Wexler, PI)
20% Concurrent Effort. To use neuropsychological tests and
MRI to identify neurobiological subtypes of schizophrenia
Dr. Peterson is directing the anatomical MRI component of
this project. Dr. Peterson is directing the anatomical MRI
component of this project.
7/01/01-6/30/06 $1,723,964
Jonathan Polan
“Maternally-directed
orienting behaviors of newborn rats”
Principal Investigator: Polan, H. Jonathan
Effort: 75 %
Period: 5/1/98 to 4/30/03
Current year amount: $ 153,337
Agency: NIMH
Grant number: MH01569
Type: K08
Myrna M. Weissman
1
R01 MH63852-01 (Weissman) 07/19/01 to 06/30/06
NIMH $822,786, First Year
Children of Depressed Mothers: a STAR*D Ancillary Study
The overall aim is to study the impact of a reduction of maternal
depressive symptoms on children’s psychiatric symptoms
and social functioning as an ancillary study to the Sequenced
Treatment Alternatives to Relieve Depression study (STAR*D).
2
R01 MH 36197-18 (Weissman) 01/01/99 - 12/31/02
NIH/NIMH $382,178
Children at High and at Low Risk For Depression
Extend assessment to third generation of persons at high risk
for MDD to determine if they demonstrate the same clinical
features as their parents. Psychophysiologic measures will
be employed to seek potential biological markers of a familial
diathesis for depressive and anxiety disorders.
1
RO1 MH60912-03 (Weissman) 09/30/99 - 08/31/03
NIH/NIMH $247,683
Genetics of Early-Onset Major Depression
A six-site cooperative project to collect a large sample of
subjects with early-onset MDD obtaining clinical data and
genetic samples aiming to map genes giving a susceptibility
to MDD.
5
R37 MH28274-24S1 (Weissman) 12/01/01 to 06/30/02
NIH/NIMH $86,051
Genetic Studies of Depressive Disorders
This is a project to understand the etiology of panic disorder
using a broad range of novel and advanced genetic and epidemiologic
approaches.
01
P30 MH60570- 03 (Shaffer) 09/24/99 to 05/31/04
NIH/NIMH $128,451 (Core Only)
Psychotherapy Core, part of Child Psychiatry Intervention
Research Center
Provide consultation to investigators on the technology of
psychotherapy research and its testing by facilitating training
in empirically based treatments and identifying opportunities
to test out psychotherapies, both in terms of adapting existing
therapies to new uses and implementing new therapies.
(Weissman)
05/01/00 to 04/30/03
NARSAD $100,000 (No cost extension)
A Potential Panic Disorder “Syndrome” Based on
Genetic Linkage
NARSAD Distinguished Investigator Award to collect additional
information on potential panic disorder syndrome which may
include a variety of bladder/kidney problems.
(Weissman)
08/01/01 to 07/31/02
Eli Lilly $150,000
Bipolar Spectrum Disorder in an Urban Primary Care Clinic
A screen of 1,000 patients coming to an Urban Primary Care
Clinic for incidence of bipolar spectrum disorder as well
as demographic characteristics, mental health treatment, social
functioning, and depressive symptoms of patients with and
without bipolar spectrum disorder.
2
R01 MH 36197-18 (Weissman) 01/01/99 - 12/31/02
NIH/NIMH $382,178 (Incl. Minority Researcher
supplement)
[NIMH Minority Researcher Supplement to: Adriana Feder]
Children at High and at Low Risk For Depression
Extend assessment to third generation of persons at high risk
for MDD to determine if they demonstrate the same clinical
features as their parents. Psychophysiologic measures will
be employed to seek potential biological markers of a familial
diathesis for depressive and anxiety disorders. The supplement
extends the high risk design to a Hispanic sample recruited
at an urban primary care clinic.
with (Feder) 07/01/02 to 06/30/04
NARSAD $30,000 Year 1
The Neurobiology of Prepubertal Onset Depression
Aims to improve understanding of the neurobiology of prepubertal
onset depression and examine the association between prepubertal
neurological findings and recurrence of depression into adulthood,
lifetime suicidality, and family psychiatric history.
1 R03 MH57813-02 with (Wickramaratne) 12/01/98 to 11/30/2001
NIH/NIMH $50,000 (No Cost Extension)
Epidemiologic Methods in Psychiatric Family Studies
Evaluate existing epidemiologic approaches to the study of
familial aggregation in psychiatric disorders and to develop
improved approaches to the design and analyses of such studies.
Total Yearly Outside Support for All Faculty: $ 9,458,000/year
(direct costs only)
SACKLER AWARDEE - FINAL REPORT
Maternal Depression: Fetal and Infant Neurobehavior
Catherine
E. Monk, PhD • Columbia University, New York, NY
July
2002
In
June, 2000, I was granted a Sackler Institute Award to support
the study of fetal characteristics associated with maternal
mood disorder. Our goal was to begin to establish a program
of research exploring the potential affects of stress, anxiety,
and depression, on fetal development. Our work is focused
on (1) finding evidence for the hypothesis that how women
function emotionally does affect the fetus and then (2) pursuing
more specifically the influence of depressed women’s
altered physiology on fetal development. With the later goal,
we aim someday to discover in utero markers for future risk
for Major Depressive Disorder (MDD). I am happy to report
that the project progressed as planned. Specifically, we generated
important data now in press with the Journal of Developmental
and Behavioral Pediatrics showing the acute transmission of
women’s stress–based physiology to the fetus.
In addition, we generated preliminary data that was instrumental
in our securing federal funding for future related studies.
In what follows, I describe more fully the work accomplished
through the support of this award.
Paper
in press showing the women’s psychologically–based
mood affecting the fetus
In this paper, entitled, The effects of women’s stress–elicited
physiological activity and chronic anxiety on fetal heart
rate, we examined the effects of pregnant women’s acute
stress reactivity and chronic anxiety on fetal heart rate.
We found that fetal heart rate changes during women’s
recovery from a stressful cognitive task performed on a computer
were associated with the women’s concurrently–collected
heart rate and blood pressure changes (r=.63, p<.05). Fetal
heart rate changes during recovery, as well as during women’s
exposure to the stressful task, were correlated with their
mothers’ trait anxiety scores (r=.39, p<.05 and r=–.52,
p<.01, respectively). Finally, a combination of measures
of women’s cardiovascular activity during recovery and
trait anxiety scores accounted for two–thirds of the
variance in fetal heart rate changes during the same recovery
period (R2=.69, p<.001). Such findings raise the possibility
that cumulative exposure to particular patterns of emotion–induced
physiological activity over the course of gestation may influence
fetal development. Moreover, our results also indicate an
influence of women’s anxiety on fetal HR. This association
suggests the possibility that there may be a trait–like
difference in fetal HR activity that is associated with a
chronic emotional state in pregnant women. Although this could
be an inherited trait, the findings here indicating the possible
acute transmission of women’s stress–elicited
cardiovascular activity to the fetus support the conceptualization
that throughout pregnancy, qualities of the in utero environment—
such as the repetition of anxiety–based alterations
in the women’s physiological activity—may influence
fetal development and contribute to the emergence of individual
differences in the fetus. Findings from this report are some
of the first ever to determine a ‘real time’ association
between fetal HR and women’s psychologically–induced
changes in cardiovascular activity. They are consistent with
a model in which differences in biobehavioral development
may be, in part, shaped in utero. Longitudinal studies focusing
on fetal, infancy, and childhood periods will help determine
whether fetal characteristics associated with women’s
emotional states during pregnancy are transitory or, in fact,
indicative of a process leading to trait–like characteristics
that have implications for the child’s long–term
health and development.
Moreover,
these findings demonstrating ‘real time’ effects
of women’s emotion–based physiological changes
on the fetus are of central importance as we pursue our research
goal to determine if depression during pregnancy affects the
fetus, and fetal development, via similar physiological pathways.
These results thus support our research goal as we investigate
this secondary agenda.
Preliminary
data used to garner federal funding:
Subject Enrollment: We recruited 126 pregnant women for the
study. Of these 126 women, so far 94 have completed the first
study session. We have run newborn assessments on the 69 babies
that have so far been born. Approximately 41% of our subjects
are diagnosed with depression, and anxiety disorder, or a
co–morbid mood disorder. Although our final analyses
are yet to be completed (and some subjects are still moving
through the longitudinal protocol) as can be seen from the
results described below, we have met our goal of recruiting
pregnant women with psychiatric diagnoses as well as healthy
controls.
Preliminary
Data:
At the outset of our research, we hypothesized that (1) maternal
depression will be associated with fetal physiological dysregulation
as indexed by a greater heart rate (HR) increase during women’s
exposure to a stressor and (2) that newborns of women depressed
during pregnancy will show altered physiology as measured
by HR changes during an orthostatic challenge.
Our
findings support our hypotheses. Specifically, preliminary
analyses suggest that, as predicted, during women’s
exposure to a laboratory “stressor”, fetuses of
depressed women show greater HR reactivity (see bar graph
of fetal HR activity related to women’s diagnostic status
below). Moreover, we now have evidence that alterations in
HR patterns are evident in the newborns of women who had mood
disorders during pregnancy (see bar graph below). Specifically,
new data indicates that newborns of women who were depressed
during pregnancy, or had anxiety disorders, do not have as
large a HR decrease to a head–down tilt challenge compared
to babies born to healthy controls. These data indicate that
we can detect differences in fetal behavior related to women’s
mood during pregnancy. In conjunction with the newborn study,
they also suggest that the alterations in HR patterns evidenced
in the fetal period related to women’s mood disorder
are not merely transitory, nor dependent on qualities of the
in utero environment. The data are consistent with the hypothesis
that mood–based alterations in women’s physiology
during pregnancy may influence the developing child’s
neurobehavioral substrate,—the building blocks of future
emotion regulation—with implications for the child’s
future risk for mental illness. Moreover, with this work,
we believe we may be in the early stages of discovering novel
and very early markers for a vulnerability to affective disorder
linked to a shared genetic predisposition of the mother and
infant. Identification of early markers for risk for mental
illness will lead to earlier therapeutic interventions, and
ultimately, to greater prevention of psychiatric illness.
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Sample
list of presentations & publications supported by the
Sackler Award
Monk,
C., Sloan, R. P., Myers, M. M, Ellman, L. & Fifer, W.P.,
The effects of women’s stress–elicited physiological
activity and chronic anxiety on fetal heart rate In Press.
Development and Behavioral Pediatrics.
Fifer,
W.P., Monk, C.M. and Grose-Fifer. Prenatal Development and
Risk. In G. Bremner and A. Fogel (Eds.), Blackwell Handbook
of Infant Development. Oxford, UK: Blackwell. (2001).
Monk,
C., Fifer, W.P., Sloan, R. P., Myers, M. M. Newborn infants
exposed to maternal psychiatric illness during pregnancy have
diminished responses to downward tiling [Abstract] Psychosomatic
Medicine; (2002) 64: 89. To be presented at the annual meeting,
American Psychosomatic Meeting, March 13-20, 2002, Barcelona,
Spain.
Monk,
C., Fifer, W.P., Sloan, R. P., Myers, M. M. Maternal depression
influences patterns of fetal reactivity. Presentation made
at the Society for Research in Child Development, April 18–22,
2001. Minneapolis, Minnesota
Other sources of funding
On October 1, 2001, I received a 5–year grant from the
National Institutes of Mental Health. The title of the project,
“Maternal Psychopathology: Fetal and Infant Neurobehavior”
is closely related to the Sackler Award as the project builds
on that initial work. Moreover, funding from the Sackler Award
was instrumental in my obtaining this federal support. Without
financial backing from the Sackler Award, we never would have
been able to generate the pilot data to compete for such an
award. Having used the Sackler grant as seed money to successfully
win federal funding, we now are in a position to build a research
program focused on detecting the earliest influences on future
risk for mental illness. We believe that these studies ultimately
will lead to the establishment of clinical interventions that
will benefit pregnant women and their future children.
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