Interpretation
of social action: an fMRI study of young adults with autism: Dr.
Charles Cartwright is Principal Investigator of this functional magnetic
resonance imaging (fMRI) study. fMRI is a process by which images of the brain
are obtained while a person is engaged in a task; these images are analyzed
to show which areas of the brain are "activated" during the task.
This research study uses the fMRI technique to identify patterns of brain
activation while participants look at pictures of faces as well as video clips
of human movements and actions. This study will help us better understand
the causes of the social impairments in autism. Dr. Cartwright is recruiting
adults (ages 18-35) who are diagnosed with autism, and a group of adults without
autism, to participate in the study.
Genetic components of autism
spectrum disorders: Dr.
Linda Brzustowicz, Dept. of Genetics, Rutgers University, is Principal
Investigator of this large NIMH-funded autism genetics study. Dr.
Charles Cartwright is Principal Investigator of the clinical assessment
component, with Dr. Barbie Zimmerman-Bier, Dept of Pediatrics, as co-investigator.
This study is the first large genetics study to look at the connection between
language development problems and autism in New Jersey. Families who
have a child with autism and another family member with a history of language
problems are being asked to provide blood samples as well as complete some
questionnaires and language tests. This research will provide important insights
into the link between language, genetics, and autism. For further information
about the study, please visit the study website at www.njlags.org
.
A model
system for the development of behavior: Dr.
Barbara Fadem is Principal Investigator of this series of studies. Marsupial
mammals, born at a developmental stage approximately equivalent to the first
trimester in human fetuses, are used in these studies to examine the role
of fetal and maternal gonadal hormones in physiological and behavioral sexual
differentiation of developing mammals.
The
pediatric resident training on tobacco project: Dr.
Norman Hymowitz is co-Principal Investigator of this NIH-funded project,
an outgrowth of his previous work which showed that pediatricians in practice
do not adequately address tobacco, that pediatric residency training programs
do not prepare residents to play a leadership role in the antismoking arena,
that, with training, pediatric residents may be effective interventionists,
and that Solutions for Smoking , a hybrid CR-ROM/Website training
program on tobacco for pediatric residents, may be an effective tool for training
pediatric residents. The current 4-year study has randomly assigned 15 pediatric
residency training programs in the New York/New Jersey Metropolitan to Special
(including Solutions for Smoking ) and Standard Training Conditions.
Interim analyses support the efficacy of Solutions for Smoking and the Special
Training Condition in increasing tobacco intervention skills and assistance
of pediatric residents.
Comparing
Three Electrode Placements to Optimize ECT: Electroconvulsive Therapy
(ECT) is a remarkably effective treatment for people suffering from major
depressive disorder. Over the years, technical improvements in the administration
of ECT have made it safe and tolerable. The cognitive side effect profile
of ECT, however, remains the principal concern of patients and practitioners.
Retrograde amnesia, which occurs to a variable extent in all patients, has
limited the use of the treatment. Research has shown that utilizing different
electrode placements on patients receiving ECT will yield different side effect
profiles. The next steps in ECT research are to optimize electrode placement
and stimulus dosing. By so doing, it should be possible to sustain clinical
efficacy with minimal cognitive effects, thereby encouraging more severely
depressed patients to accept this effective treatment. Dr.
Charles Kellner is Principal Investigator of an NIMH-funded multi-center
study comparing the efficacy and safety of three electrode placements: bitemporal,
right unilateral, and bifrontal. Dr. Georgios
Petrides is Co-Principal Investigator. The study is examining the antidepressant
and cognitive effects of an index course of ECT in 360 patients with a major
depressive episode at four sites over four years. Patients are followed for
two months after the ECT course to assess the possible lasting differential
effects on cognition and quality of life of the three electrode placements.
Gingko
Biloba for ECT-Induced Memory Deficits: Dr.
Charles Kellner is Principal Investigator of this study. Electroconvulsive
therapy (ECT) is a powerful treatment for major depression. However, it has
the bothersome side effect of cognitive impairment, including some types of
memory functioning. The herbal preparation Gingko Biloba (GB) has been shown
in recent studies to aid cognitive function. In this NIH-funded study, we
hypothesize that patients receiving ECT plus GB will experience reduced cognitive
effects during and following ECT compared to those receiving ECT plus placebo.
In addition, we believe treatment with GB will be both safe and well tolerated.
Pharmacogenetics
of Ziprasidone Response: In this Stanley Foundation-sponsored study,
Dr. Georgios Petrides is looking to
1) identify common inheritance patterns in people with schizophrenia who are
successfully treated with the antipsychotic medication ziprasidone, and 2)
identify common inheritance patterns that are associated with side effects
of treatment with ziprasidone, including cardiac effects and weight gain.
In order to accomplish these goals, we propose to collect DNA samples from
patients who are beginning treatment with ziprasidone. We will collect clinical
data on psychiatric symptoms and side effects such as cardiac repolarization
abnormalities and weight gain on all patients.
Risk
Perception and the Psychobiological Sequelae of Vaccination : Dr.
Karen Quigley is Principal Investigator of this Department of Veteran's
Affairs-funded study of how bioterrorism as a threat influences risk perceptions
and psychobiological responses to vaccination. We do not know how bioterrorism
concerns may influence the general public's response to vaccination including
how these concerns could change a person's perceptions of the risks and benefits
of medical procedures (like vaccination), and other technologies. In addition,
the studies will examine how bioterrorism concerns affect symptom reports
and mood after vaccination, and the immune system response to vaccination.
Finally, we will address how individual differences such as age and trait
negative emotionality alter these perceptual and biological outcomes. Study
co-investigators from NJMS include Drs. Susan Santos (School of Public Health)
and Drew Helmer (Internal Medicine).
Prospective
Study of Functional Status in Veterans at Risk for Unexplained Illness :
Dr. Karen Quigley is Principal
Investigator of a Department of Veteran's Affairs-funded study of pre-military
deployment predictors of post-deployment medically unexplained symptoms. Medically
unexplained symptoms have been reported by veterans of numerous previous hazardous
deployments including peace-keeping missions. The study will examine which
pre-deployment psychosocial variables (such as personality, social support
and coping style) and biological stress responses (such as cardiovascular
and endocrine responses to a laboratory stressor) predict a greater tendency
to report unexplained physical symptoms, and poor self-reported health at
3 months and 1 year following a deployment. This longitudinal study, with
NJMS co-investigators, Drs. Karen Raphael
and Shelley Weaver (Neuroscience) will provide important information about
which individuals are at greatest risk for post-deployment unexplained health
problems.
Fibromyalgia
and Depression: Dr.
Karen Raphael is Principal Investigator of this
NIH-funded community-based family study, designed to investigate factors underlying
the comorbidity of major depressive disorder and fibromyalgia, a syndrome
involving widespread pain of unknown origin. It is now in its analytic phase.
Findings to date indicate that major depressive disorder and fibromyalgia
share familially-mediated risk factors.
Mechanisms
underlying medically unexplained facial pain: Dr.
Karen Raphael is Principal Investigator of this
NIH-funded study examining the role of sleep bruxism (grinding or clenching
of the teeth at night), waking stress-induced bruxism, and abnormal central
nervous system pain processing mechanisms in the maintenance of myofascial
face pain, a prevalent type of temporomandibular disorder (TMD). UMDNJ study
co-investigators include Dr. Karen
Quigley (NJMS Dept. of Psychiatry) and Dr.
Scott Diehl (NJDS).
Interleukin
(IL)-2 and stereotypic behavior: Dr.
Steven Zalcman and others have shown in rodents that peripheral injections
of interleukin (IL)-2 alter dopamine release and turnover in the mesocorticolimbic
and mesostriatal systems. In vitro studies have similarly shown that IL-2
is a potent modulator of central dopamine release and that it modulates membrane
conductance in dopaminergic neurons. It is thus of unique interest that IL-2
is implicated in the etiology and pathogenesis of psychopathological outcomes
associated with aberrations in the mesolimbic and mesostriatal systems, notably
psychosis, schizophrenic-like behavior, and cognitive abnormalities. A common
dimension of these abnormalities is the expression of repetitive motor stereotypies.
Dr. Zalcman is the Principal Investigator of an NIH-funded study examining
the effects of IL-2 on the expression of stereotypic behavior and identifying
mechanisms underlying these effects.
Psychoneuroimmunology
of T Cell Activation: There is a consensus that immunological factors
can induce and may be involved in the etiology and pathogenesis of various
psychiatric disorders. For example, activated T helper lymphocytes (TH cells)
are implicated in psychopathological outcomes involving repetitive behaviors
and that are associated with aberrations in the mesocorticolimbic and mesostriatal
systems (notably psychosis, schizophrenic-like behavior, autism, cognitive
deficits). However, there are no systematic analyses of the neurobehavioral
consequences of TH cells. Dr. Steven Zalcman,
in collaboration with Dr. Nicholas Ponzio in the Department of Pathology and
Laboratory Medicine, is using a novel experimental strategy to systematically
examine the neurobehavioral consequences of T cell activation by examining
the neurobehavioral consequences TH cells lines adoptively transferred into
syngeneic recipients. This permits a detailed analysis of the behavioral consequences
of T cell activation, and identification of the underlying neural mechanisms
and signaling pathways.
Cytokines
and Stereotypical Motor Activity: Role of Development and Monoamine Receptors:
A core dimension of autism is the presence of stereotypic motor behaviors,
particularly in unstructured settings. There is evidence that an early-life
autoimmune process (including altered T helper (TH)-cell activity) plays a
role in the disease process in a subset of patients. Supporting this hypothesis,
behavioral (stereotypic motor activity), cognitive (deficits in attention,
learning), and neurochemical (monoamine) abnormalities evident in autistic
children are induced by TH1-cytokines (particularly interleukin-2). Dr.
Steven Zalcman, in collaboration with Dr.
Charles Cartwright in the Dept. of Psychiatry, ise developing an animal
model of autism by identifying critical neonatal periods during which cytokine
treatment produces long-lasting increases in vulnerability to stereotypic
behavior and altered neuronal response patterns (e.g., in dopamine containing
cells). Linking immune activation, monoamine dysfunction and critical developmental
periods with stereotypic behavior is novel, and will shed light on mechanisms
underlying aspects of autistic behavior.
Role
of Limbic-Midbrain Axis in Aggressive Behavior: Dr.
Steven Zalcman is co-investigator of this study, headed by Dr. Allan Siegel
in the Departments of Neurology & Neuroscience and Psychiatry. The long-term
goal is to identify the neural circuitry and neurochemical and neurophysiological
mechanisms that underlie the expression and control of rage and aggressive
behavior. The primary focus of the present project is to identify and characterize
the roles of serotonin and cytokines in the medial hypothalamus in regulating
these forms of aggression. The rationale for this work is based upon our studies
indicating that, in the medial hypothalamus, serotonergic receptors and cytokines
(IL-1 and IL-2) powerfully modulate defensive rage behavior in the cat. T
he discovery that brain cytokines modulate defensive rage provides a new research
direction, which will shed light on the neural mechanisms mediating the expression
and control of aggression and rage.
Contribution
of immunological mechanisms to autism spectrum disorders: Dr.
Steven Zalcman is co-Principal Investigator of this study, headed by Dr.
Nicholas Ponzio in the Department of Pathology and Laboratory Medicine. Maternal
immune activation is thought to increase vulnerability to psychiatric disorders
involving repetitive and stereotypic behavior (notably schizophrenia and autism).
However, the factors that mediate these effects are not known. Since one candidate,
interleukin (IL)-2, also potentiates stress- and psychostimulant-induced activity
and increases the expression of stereotypic motor behavior (Zalcman et al.,
1998; Zalcman, 2001, 2002), the study seeks to determine the effects of maternal
exposure to IL-2 on behavior and neuronal activation patterns in offspring.
This study could have significant implications on our understanding of the
long-term effects of abnormally increased maternal levels of IL-2 (and other
cytokines) on vulnerability to neurobehavioral abnormalities associated with
dimensions of schizophrenia and autism.
