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RESEARCH SITES OF THE
CLINICAL RESEARCH TRAINING PROGRAM
IN
BIOLOGICAL AND SOCIAL/DEVELOPMENTAL PSYCHIATRY
AT JUDGE BAKER CHILDREN'S CENTER
DEPARTMENT OF PSYCHIATRY
HARVARD MEDICAL SCHOOL
CLINICAL RESEARCH TRAINING PROGRAM
IN BIOLOGICAL AND SOCIAL/DEVELOPMENTAL PSYCHIATRY
AT JUDGE BAKER CHILDREN'S CENTER/DEPARTMENT OF PSYCHOLOGY, HARVARD MEDICAL SCHOOL
OVERVIEW:
This interdisciplinary training program is designed to foster greater understanding of, and
competence in, clinical research. It focuses on clinically relevant projects in either the biological or the
social/developmental domains, and encourages intellectual exchange between the two approaches.
Clinical research is broadly defined as research involving clinical populations or research otherwise
bearing on normal and pathological conditions relevant to psychiatry.
This full-time, two-year, postdoctoral program has been in operation for thirty years. It is open to
individuals who have either an M.D. or a doctoral degree and who are U.S. citizens or permanent
residents. Core components of the program include affiliation with one of our training sites, the
implementation of an independent investigation (working with a specific research preceptor), a weekly
integrated academic seminar led by the co-directors, and opportunities for course work at Harvard. The
faculty and research preceptors are involved in a diverse number of funded social/developmental and
biological investigations. These investigations provide a staggering array of opportunities for
postdoctoral training, including experience in brain imaging techniques, psychopharmacology research,
psychiatric epidemiology, and longitudinal studies of development.
This training program is funded by the National Institute of Mental Health. Appointments are one
year, renewable to two. Stipends are awarded on the predetermined NIMH award pay scale. The
application deadline is rolling; applicants should refer to the application form for a complete list of
required documentation. We especially encourage women and minority applicants. Stipends are
awarded on the predetermined NIMH award pay scale. All applicants must be US citizens or permanent
residents.
OBJECTIVES AND GOALS:
The goals and objectives of the Clinical Research Training Program (CRTP) continue to center on
offering trainees a more sophisticated understanding of the research tools that are relevant to clinical
psychiatric situations than trainees could acquire without this grant. The trainees study experimental
designs, scientific logic and the intricacies of present day statistics and computer processing techniques
in order to implement a research project; they then use this scientific and methodological background to
examine populations in a way that will determine the most promising areas of inquiry and the areas in
which the need for achievement is greatest. The program also focuses on the possible applications of the
methods of major areas of psychiatric research to other major areas of study.
The CRTP offers a concentrated two years of didactic and ‘hands-on’ research experience to the
fellows with the specific goal of developing bridges between their prior training and clinical research in
psychiatry. Each cohort participates in a two-year cycle of the interdisciplinary seminar and has time to
design, implement, analyze, and interpret his/her own project which is carried out with the supervision
of a specific preceptor. Since this training design has been successful, leading to numerous publications
and new grants for trainees, we plan to continue this basic approach. Trainees vary from just graduated
PhDs or MDs to individuals with several years of experience. Both groups have profited from our
intensive program, and the mix has also benefited the program, contributing to the liveliness of the
research seminar.
It is our belief that true depth of knowledge is best obtained through close and continuing contact
with an experienced scientist working in the trainee’s area of interest. To accomplish this, we require (at
a minimum) a two-year apprenticeship with an experienced, productive investigator working in an
ongoing, active, and high-quality research program. We believe that our program provides trainees with
an unusually strong and diverse group of preceptors and research projects.
FACULTY:
Program Directors: Martha E. Shenton, PhD, Robert W. McCarley, MD Robert J. Waldinger, MD
Jerome Kagan, PhD
Training faculty/research preceptors:
J. Stuart Ablon, PhD; Arthur J. Barsky, MD; William R. Beardslee, MD; Harold S. Bursztajn, MD;
Bruce Cohen, MD, PhD; Joseph T. Coyle, MD; Curtis K. Deutsch, PhD; Jill M. Goldstein, PhD; David
Henderson, MD; David B. Herzog, MD; Jill M. Hooley, PhD; Alan M. Jacobson, MD; David C.
Jimerson, MD; Jerome Kagan, PhD; Deborah Levy, PhD; Karlen Lyons-Ruth, PhD; Dara S. Manoach,
PhD; Robert W. McCarley, MD; Kathleen McCartney, PhD; Jane M. Murphy, PhD; Lisa M. Najavits,
PhD; Charles Nelson, PhD; Margaret Niznikiewicz, Ph.D.; Timothy J. O’Farrell, PhD; Scott P. Orr,
PhD; David Pauls, PhD.; Tracey L. Petryshen, PhD Harrison G. Pope, Jr., MD; Scott L. Rauch, MD;
Dean Salisbury, Ph.D.; Carl Salzman, MD; Larry J. Seidman, PhD; Martha E. Shenton, PhD; Jordan
Smoller, MD; Catherine Snow, PhD; Kevin M. Spencer, PhD, Nancy Snidman, PhD; Edward Z.
Tronick, PhD; Robert J. Waldinger, MD; John R. Weisz, Ph.D., ABPP; Cynthia G. Wible, PhD
PROJECT SITES:
Beth Israel Hospital
Brigham and Women’s Hospital
Brockton/West Roxbury VA Medical Center
Cambridge Hospital
The Children’s Hospital
Harvard Graduate School of Education
Harvard Medical School
Harvard School of Public Health
Harvard University - Dept. of Psychology
Joslin Diabetes Center
Judge Baker Children’s Center
Massachusetts General Hospital
Massachusetts Mental Health Center
McLean Hospital
Shriver Center for Mental Retardation
FOR MORE INFORMATION CONTACT:
Program Coordinator
Clinical Research Training Program
Judge Baker Children’s Center
53 Parker Hill Avenue
Boston, MA 02120-3225
Phone: (617) 278-4293
Fax: (617) 232-8399
Email: [email protected]
RESEARCH SITES OF THE
CLINICAL RESEARCH TRAINING PROGRAM
IN BIOLOGICAL AND SOCIAL/DEVELOPMENTAL PSYCHIATRY
AT JUDGE BAKER CHILDREN'S CENTER/DEPARTMENT OF PSYCHOLOGY, HARVARD MEDICAL SCHOOL
The diverse sites cover biological, developmental, psychosocial, and epidemiological domains. All
of the following research sites represent funded projects, usually through federal sources. In our brief
descriptions of each setting and its opportunities offered, we note collaborations with other training
faculty.
The Psychotherapy Research Program
Preceptor: AJ. Stuart Ablon, PhD
Massachusetts General Hospital
The Psychotherapy Research Program in the Department of Psychiatry at Massachusetts General
Hospital was established in 1999 to study empirically both the process and outcome of psychotherapy
for a range of psychiatric disorders with J. Stuart Ablon, Ph.D. as the Director, Raymond Levy, Psy.D.
as the Clinical Director, and Carl Marci, M.D. is the Director of Social Neuroscience. The group is
composed of psychiatrists, psychologists, post-doctoral Fellows and Research Assistants with a broad
range of years of clinical and research experience. In the seven years of its existence, the program has
expanded significantly beyond the original members to a cohesive group of 15 with wide-ranging
interests. The group meets weekly during the academic year.
The core focus of the Psychotherapy Research Program is on understanding process correlates of
outcome in psychotherapeutic treatments. There are currently five members holding grants from NIMH,
the American Psychoanalytic Association, the International Psychoanalytic Association and the National
Center for Complementary and Alternative Medicine. Increasing membership has lead to broadening
research interests within the area of psychotherapy research, and a variety of theoretical orientations are
represented in the group. Current studies range from studying process correlates of outcome in longterm psychodynamic psychotherapy, to studying the impact of enhanced versus limited relational
interactions in acupuncture treatment of patients with irritable bowel syndrome, to studying the impact
of the couch on degree of analytic process created in psychoanalyses conducted both sitting up and lying
down, to studying the degree of physiologic concordance in psychotherapy dyads and its relationship to
more traditional measures of empathy.
The Psychotherapy Research Program also routinely welcomes visitors who are invited to present their
own research to the group with the aim of fostering potential collaboration and the continuing education
of group members.
Contact:
J. Stuart Ablon, Ph.D.
Associate Clinical Professor of Psychiatry, Harvard Medical School;
Director, Psychotherapy Research Program
Dept of Psychiatry, Massachusetts General Hospital
151 Merrimac Street
Suite 300
Boston, MA 02114
Phone: (617) 643-6024
Fax: (617) 643-6050
Email: [email protected]
The description and treatment of somatoform disorders
Preceptor: Arthur Barsky, M.D.
Brigham and Women’s Hospital
My research focuses on the psychiatric, cognitive, and perceptual factors which
influence the experience and reporting of bodily distress and somatic symptoms, both in
medical and in psychiatric patients. Currently, I am conducting a randomized, controlled,
effectiveness trial of cognitive behavior therapy (CBT) for hypochondriacal patients in a
large primary care practice. Another ongoing study uses a randomized, controlled design
to compare the efficacy of fluoxetine, CBT, and their combination to treat DSM IV
hypochondriasis. We are also studying the use of cognitive and behavioral techniques to
palliate the symptoms of rheumatoid arthritis in a randomized, controlled trial comparing
CBT, relaxation training, and psychoeducation. Finally, I am interested studying
somatoform disorder patients with functional brain imaging, and am currently conducting a
pilot study of fMRI for patients with conversion visual deficits.
Contact:
Arthur Barsky, M.D.
Clinical Research Training Program Preceptor
Director of Psychiatric Research
Division of Psychiatry
Brigham and Women's Hospital
75 Francis Street
Boston, MA 02115
Phone: (617) 732-5236
Fax: (617) 278-6907
Email: [email protected]
The Preventive Intervention Project for Children of Parents with Affective Disorder [P.I.P]
Preceptor: William R. Beardslee, M.D.
Judge Baker Children’s Center
This long term study seeks to evaluate and promote preventive intervention strategies for children of
parents with affective disorders. The P.I.P. project is based on Dr. Beardslee’s prior work that identified
high rates of depression and other affective disorders in the children of depressed parents, and more
importantly, also identified the resilient characteristics of children who did well. Dr Beardslee developed
two programs to help families with parental depression promote these resilient traits in their children.
The first program was a clinician-based psychoeducational intervention, consisting of 6 to 8 sessions
followed by periodic refresher sessions. It involved the entire family and was aimed at enhancing the
resiliency of youngsters through the presentation of cognitive material and linking of this material to the
individual life experience of the family. The second program presented similar educational material but
in a lecture format where there was no opportunity to connect the material to the individual life
experiences of each family. Assessment with semi-structured interviews took place pre and post
interventions and then for several years at approximate 8 month intervals.
All families have been followed through at least time 8 and this entire data set is available for analysis.
We have found that both groups (clinician-based and lecture) benefited from the interventions, although
those in the clinician-based format demonstrated gains in more areas. Our most significant finding was
that the positive changes in behaviors and attitudes attributed to the interventions are sustained over a
long period of time.
The current focus of P.I.P. is to disseminate the knowledge gained through this research. To this end, the
original intervention manual is undergoing a significant revision and will soon be available for training
and research purposes. In addition, to broaden the reach of this project, we are currently working with a
web-site developer to put this revised manual on the internet. Analysis continues on our data set. We are
looking at the impact of having a depressed parent on the transition to young adulthood in study
participants who are now over the age of 18. We are continuing to explore the mechanisms of action for
effective preventive intervention and the characteristics of families that are able to benefit most. We also
continue to be interested in the effects of class, culture, marital status, and poverty on family response.
This April we will be presenting research findings from the Preventive Intervention Project at the
meeting of the Society for Research in Child Development.
Teens Achieving Mastery over Stress [TEAMS]
Preceptor: William R. Beardslee M.D.
Judge Baker Children’s Center
The TEAMS project is an NIMH-funded multi-site study that aims to evaluate the efficacy of a
cognitive-behavioral group intervention designed to prevent depression in at-risk adolescents. This
project was initially funded in 2004 and has recently been refunded to continue for an additional 4 years.
In the first phase of the project, half the enrolled teens participated in short term cognitive behavior
groups followed by periodic refresher sessions. They were assessed pre-participation and then 4
additional times over the next 3 years. The remaining teens only participated in the assessments. Initial
findings suggest that these groups are effective. In the second phase of the study, we plan to follow our
original TEAMS sample across the important transition to young adulthood. We hope to evaluate longterm effects of our prevention groups on participants as they negotiate the many challenges of young
adulthood.
Dr. Beardslee collaborates with numerous other research training faculty including Drs. Earls, Jacobson,
Noam, and Selman. This setting can provide excellent opportunities for clinical research Fellows to
learn about and pursue family-based preventive interventions for affective disorders. We have had a
number of different Fellows perform quite successfully in the program over the last several years.
Contact:
William R. Beardslee, M.D.
Clinical Research Training Program Preceptor
Judge Baker Children's Center
53 Parker Hill Avenue
Boston, MA 02120
Phone: (617) 278-4292
Email: [email protected]
Psychodynamically informed research regarding conflicts of interest, informed consent, and
ethical and clinical-decision making
Preceptors: Harold S. Bursztajn, M.D. & Thomas G. Gutheil, M.D.
Massachusetts Mental Health Center & Beth Israel Deaconess Hospital
Since the Program in Psychiatry and the Law was founded in 1982 it has been an incubator of
a plethora of ground breaking psychodynamically informed empirical research publications as
well as a risk management, ethics and forensic consultation resource. Long standing interests
include medical decision making, the informed consent process, and medical and mental health
ethics. A recent focus has been the analysis of potential conflicts of interest including industry
ties influence on organizational and individual decision making. Research contributing to the
protection of vulnerable populations, e.g. children, the chronically mentally ill and the impaired
elderly is an ongoing program value. In addition to the preceptors, resources include consulting
psychiatrists, psychologists, social workers, social studies researchers, attorneys, chaplains, judges
and ethicists in a wide variety of community based clinical and forensic practice sites ranging
from hospice care to the courtroom. This is a training site for research fellows interested in
developing and implementing dynamically informed empirical studies contributing to more
meaningful decision making processes in clinical care. The individual researcher’s interests and
qualifications will be matched with a variable range of resources.
Contact:
Harold J. Bursztajn, M.D.
Clinical Research Training Program Preceptor
Clinical Associate Professor
Harvard Medical School Department of Psychiatry @ Beth Israel Medical Center &
Massachusetts Mental Health Center
Program in Psychiatry and the Law
96 Larchwood Drive
Cambridge, Ma 02138
617-492-8388 or 617-803-5235
[email protected]
Neurobiology of Psychiatric Disorders
Preceptor: Bruce M. Cohen, M.D., Ph.D.
McLean Hospital
This program of research supports a multidisciplinary team of basic and clinical scientists devoted to
understanding the causes and developing new treatments for major psychiatric disorders, especially
mood, psychotic and anxiety disorders. Techniques and discoveries arise from clinical, laboratory and
brain imaging components. Dr. Cohen collaborates with Drs. William Carlezon, Ned Buttner, Cecile
Beguin, Elena Chartoff, Ed Meloni, Beth Murphy, Dost Ongur, Brent Forester, Brian Brennan, Elizabeth
Quattrocki Knight, Blaise Frederick, Mark Kaufman, Mike Rohan and Nicholas Lange, among others, in
these projects.
Our animal studies point to an important role for the peptide neurotransmitter dynorphin, acting
through kappa receptors, in the determination of mood state. We are working to synthesize and test
agents that act at kappa receptors to produce mood stabilizing effects. We have promising leads on new
ways to treat bipolar disorder through replacement of dysfunctional cells or cellular elements. We have
initiated a model using C. elegans to study current drugs and discover new targets for novel treatments
of bipolar disorder and schizophrenia. Early findings implicate the insulin signaling pathway and trace
amine signaling.
Our Brain imaging emphasizes the study of brain chemistry and activity related to psychiatric
illness and treatment response. Imaging results have suggested the value of LFMS (Low Field Magnetic
Stimulation) and suggest the use of mitochondrial supplements and glutamatergic agents to correct
abnormal metabolic findings in bipolar disorder and schizophrenia.
The pace of discovery of risk genes for human illness, including psychiatric disorders, has
accelerated. We are collaborating with the Broad Institute at MIT and Harvard to phenotype patients
and identify genes that determine the risk for developing psychiatric illness and response to treatment.
At present, over 250 patients are volunteering for these studies yearly.
Our Clinical Trials effort is based on our laboratory and brain imaging findings. Trials of kappa
modulators are moving from the laboratory to the clinical arena. Ongoing or follow-up trials of
promising early studies include the pursuit of LFMS, the treatment of bipolar disorder with
mitochondrial supplements and bipolar depression with glutamatergic agents. We have initiated studies
to evaluate whether rtfMRI neurofeedback can be used in the treatment of mood and anxiety disorders.
Contact:
Bruce M. Cohen, M.D., Ph.D.
Clinical Research Training Program Preceptor
Director, Shervert H. Frazier Research Institute
McLean Hospital
115 Mill Street
Belmont, MA 02178
Phone: (617) 855-3227
Fax: (617) 855-3670
Email: [email protected]
Basic Mechanisms of Selective Neuronal Vulnerability in
Neuropsychiatric Disorders
Preceptor: Joseph T. Coyle, M.D.
Massachusetts General Hospital Neuroscience Center, Charlestown
This Laboratory is studying the role of the excitatory neurotransmitter, glutamate, in
the pathophysiology of neuropsychiatric disorders. For over thirty years, it has pioneered
research on the mechanisms whereby activation of glutamate receptors causes selective
neuronal degeneration. Current research focuses on the role of NMDA receptor
dysfunction in the pathophysiology of schizophrenia and bipolar disorder. Specifically, we
manipulate the expression of putative risk genes in mice and define the neurochemical and
behavioral consequences with the goal of using appropriate models to develop new
treatments. The project site is the McLean Hospital Mailman laboratories. There are
several training opportunities in this new research facility for postdoctoral fellows
interested in molecular models of human neuropsychiatric disorders.
Contact:
Joseph T. Coyle, M.D.
Clinical Research Training Program Preceptor
Eben S. Draper Professor of Psychiatry and of Neuroscience
Administration Building 218
McLean Hospital
115 Mill Street
Belmont, MA 02478
Phone: (617) 855-2101
Fax: (617) 855-2705
Developmental Psychobiology
Preceptor: Curtis K. Deutsch, Ph.D.
Eunice Kennedy Shriver Center for Mental Retardation
and McLean Hospital
The research focus at this site is the relationship between craniofacial dysmorphology
and psychiatric illness. Since craniofacial and brain morphology simultaneously arise
from common embryonic primordia and are molded by shared forces, it is plausible that a
pathologic process can results in not only brain maldevelopment but also dysmorphology
of the head and face. Specific classes of dysmorphology may delineate brain alterations in
psychiatric disorders. Quantitative and clinical methods are utilized in assessing brain and
craniofacial dysmorphology in patients with schizophrenia, bipolar disorder, and autism.
Quantitative dysmorphology measures employ new 3D surface scans, imaged by
stereophotogrammetry. Dysmorphic phenotypes are then studied in psychosis along with
complementary neurobehavioral endophenotypes, in collaboration with Dr Deborah Levy.
Both psychosis and autism are investigated within nuclear families, permitting
modeling of familial transmission patterns, and investigations of molecular genetics.
Contact:
Curtis K. Deutsch, Ph.D.
Clinical Research Training Program Preceptor
Director
Psychobiology Program
Eunice Kennedy Shriver Center
200 Trapelo Road
Waltham, MA 02154
Phone: (781) 642-0163
Fax: (781) 642-0032
Email: [email protected]
Clinical Neuroscience Laboratory of Sex Differences in the Brain
Preceptor: Jill M. Goldstein, Ph.D.
Brigham and Women’s Hospital and Massachusetts General Hospital
Dr. Goldstein’s program of research is called the Clinical Neuroscience of Sex
Differences in the Brain. The work of the team focuses on characterizing and explaining
sex differences in the healthy brain and how this deviates in psychiatric disorders that
exhibit sex differences in incidence. The team consists of an interdisciplinary team of
investigators integrating structural and functional brain imaging studies,
psychophysiology, neuroendocrine studies of hormones and brain function, genetics, and
collaborative efforts with animal investigators studying genes, hormones and the brain.
Current work is focused on investigating fetal antecedents to sex differences in adult
onset psychiatric disorders with fetal origins, such as schizophrenia, bipolar psychoses
and depression. In addition, the team is investigating shared fetal antecedents to the comorbidity of depression with cardiovascular disease and associated metabolic syndrome
conditions, including diseases associated with obesity. Studies include large scale
epidemiologic samples in whom we are investigating fetal hormonal programming of
chronic disease in adulthood and clinical studies using structural and functional MRI to
test hypotheses regarding the impact of one’s sex on brain structure and function.
Current studies are investigating the stress response circuitry, reward circuitry implicated
in food motivation, and memory and working memory deficits implicated in the above
disorders. Hypotheses focus on the role of hormones, genes and inflammatory factors.
www.cnl-sd.bwh.harvard.edu
(site still under construction as of 010109)
Contact:
Jill M. Goldstein, Ph.D.
Clinical Research Training Program Preceptor
Professor of Psychiatry and Medicine, HMS
Director of Research
Connors Center for Women's Health & Gender Biology
Brigham & Women's Hospital
Division of Women's Health
One Brigham Circle - 3rd floor
1620 Tremont St.
Boston, MA 02120
Tel.617-525-7517; admin asst 617-525-7929
Fax: 617-525-7746
Email: [email protected]
Freedom Trail Clinic
Preceptor: David D. Henderson, M.D.
Massachusetts General Hospital
The Schizophrenia Program of the Massachusetts General Hospital (MGH) offers a wide range of
clinical services and is committed to providing the best possible care to patients. In addition, we offer a
unique international consultation service to patients and their families. Continuing care is provided
under the supervision of faculty members at the Freedom Trail Clinic because optimal treatment for
individuals with schizophrenia requires a community-based team approach which integrates many
services including: case management, outreach, emergency services, day treatment, substance abuse
treatment, social clubs, residential programs and vocational services. The Program also has a strong
commitment to engage in cutting edge research to better understand the pathophysiology of
schizophrenia and to develop better treatments for this devastating illness. The research mission is
carried out in four major domains: psychopharmacology, neuroimaging, genetics and cognitive
behavioral therapy.
Because of unhealthy lifestyle behaviors, medication side effects, and poor access to medical care,
approximately half of individuals diagnosed with a severe mental illness develop a serious medical
condition. Pharmacological research related to our Weight Loss and Diabetes Prevention Programs
investigates the medical side effects of currently available drugs and examines the use of medications to
prevent or improve medical complications in our patients. This includes pioneering work investigating
the mechanisms by which certain antipsychotics causes weight gain and may increase the risk for
diabetes. The Schizophrenia Program of MGH offers a comprehensive approach to weight reduction and
healthy lifestyle behaviors. High rates of serious medical conditions and a shortened life expectancy
have long been associated with chronic mental illness, particularly schizophrenia. Recent advances have
been associated with better clinical outcomes and a dramatic decline in medication-induced side effects.
Weight gain is a frequent side effect of psychiatric medications, so individuals who take these
medications are particularly vulnerable to obesity and associated illnesses including type II diabetes
mellitus, hypertension, and coronary heart disease. The Weight Loss and Diabetes Prevention Program
is tailored to the needs of individuals with serious mental illness and provides state-of-the-art
interventions for weight loss, diabetes prevention, improved cardiovascular fitness, and better overall
health.
Dr. Henderson’s main research interests focus on psychopharmacological and antipsychotic agents in
the treatment of schizophrenia, impacts of antipsychotic agents on metabolic anomalies and glucose
metabolism. Several clinical trials have been completed and we currently have a number of on going
studies along with several protocols soon to be initiated. We have been studying the effects of
antipsychotic agents on glucose metabolism, weight gain, and hyperlipidemia. We are also studying
clinical interventions to reduce or reverse the insulin resistance and weight gain associated with some of
these agents.
Dr. Henderson also has focused on international psychiatry in areas of mass violence such as Rwanda,
Cambodia, East Timor, Bosnia, and Peru. He has conducted several projects related to the training
primary care clinicians on the effects of violence and the psychiatric care of mentally ill patients and
patients experiencing the consequences of violence. This work has been conducted in conjunction with
the MGH International Division of Psychiatry and the MGH Harvard Program in Refugee Trauma.
Contact:
David C. Henderson, M.D.
Massachusetts General Hospital
Harvard Medical School
Freedom Trail Clinic
25 Staniford Street
Boston, MA 02114
Phone: (617) 912-7800
Fax: (617)723-3919
Email: [email protected]
Longitudinal Study of Anorexia and Bulimia Nervosa
Preceptor: David B. Herzog, M.D.
Massachusetts General Hospital
Dr. Herzog is the Principal Investigator of the Longitudinal Study of Anorexia and
Bulimia Nervosa, a prospective, naturalistic examination of 246 women with anorexia
nervosa (AN) and bulimia nervosa (BN). Participants were interviewed every six months
and were followed for eleven years. According to the DSM-IV classifications, the sample
comprises 51 women with AN-restricting subtype, 85 women with AN-binge/purge
subtype, and 110 women with BN. The study aims are: 1) to map the course and outcome
of each disorder; 2) to assess prognostic factors; and 3) to assess the relationship between
eating disorders and comorbid disorders. To date, several secondary analyses have been
conducted using data from this cohort.
Currently, the research team is collaborating with the Neuroendocrine Unit at MGH on
studies assessing and treating bone loss in adolescents and adults with AN. We are also
embarking on examinations of structural and functional neuroimaging and
neuropsychological functioning in adolescents and adults with AN.
Contact:
David B. Herzog, M.D.
Director, Harris Center for Education and Advocacy in Eating Disorders at Massachusetts
General Hospital
2 Longfellow Place, Suite 200
Boston, MA 02114
Phone: (617) 726-8470
Email: [email protected]
Website: www.harriscentermgh.org
Neuroimaging studies of Emotion Processing in Depression and Borderline Personality Disorder
Preceptor: Jill M. Hooley, D.Phil.
Harvard University, Department of Psychology
Current projects at this site are outlined below. Opportunities exist for research fellows to participate
in our ongoing research activities or to develop new research studies in these areas.
(1) Neuroimaging studies of vulnerability to depression. A large body of evidence has
demonstrated that high family levels of expressed emotion (EE) are reliably associated with
increased risk for relapse in patients suffering from both schizophrenia and depression. Ongoing
studies are using fMRI to explore how healthy people and people who are vulnerable to depression
process criticism and praise from their mothers. The extent to which criticism perturbs information
processing in people with depression is also being examined.
(2) Emotion processing in borderline personality disorders. Current projects are using
neuroimaging to examine how people with borderline personality disorder process affectively
challenging social stimuli.
(3) A final focus of interest concerns the topic of pain sensitivity. We have documented aberrant
pain sensitivity in healthy people who have a relative with schizophrenia. Current projects are
exploring pain perception in people who engage in self-harming behaviors such as cutting and
burning
Contact:
Jill M. Hooley, D.Phil.
Clinical Research Training Program Preceptor
Professor of Psychology
William James Hall
Harvard University
33 Kirkland Street
Cambridge, MA 02138
Phone: (617) 495-9508
Email: [email protected]
Psychological Aspects of Diabetes Mellitus
Preceptor: Alan M. Jacobson, M.D.
Joslin Diabetes Center
These studies have three related aims: 1) to identify the psychological and quality of
life impacts of diabetes mellitus, 2) to evaluate the role of psychosocial risks and protective
factors in medical outcomes of diabetes and related illnesses and 3) to develop innovative
behavioral and educational methods to improve diabetes outcomes. Several
programmatically related studies are now under way by Dr. Jacobson and colleagues.
One major focus of the work is currently on the development of cognitive behavioral
methods for use in treating medical patients. In this study, adult patients with diabetes
mellitus are randomly assigned to a cognitive behavioral therapy group program and a
controlled educational condition. Patients are followed over a one-year timeframe to
evaluate the effect of the intervention on patient knowledge, attitudes, behavior change,
self care activities and glycemic control. In related studies this research is also focusing on
the development of teaching methods that can be used to train nurse educators in cognitive
behavioral methods in order to incorporate them in their educational programs with
diabetic patients. A collaboration has been developed with a research group at the Free
University of Amsterdam to carry out parallel studies across cultures.
A second study focuses on the relationship of diabetes to depressive disorders.
Previous research has suggested that diabetic patients experience a high prevalence of
depression. Our work has suggested that patients with early onset of diabetes prior to age
5 are at special risk. This group has also been shown to experience decrements in
cognitive functioning. We have speculated that cognitive and affective problems are
related and caused by subtle brain damage secondary to hypoglycemia. In the current
study, we are evaluating patients with very early onset of diabetes and differing histories of
severe hypoglycemia. Using SPECT and MRI we have found initial indications of
hypometabolism in the frontal cortices of these patients. The current project is amplifying
and extending these initial observations. If these results hold, further studies will examine
the relationship of acute hypoglycemia and brain physiology and the potential role of
similar biological mechanisms in patients whose diabetes onset occurred after age 5.
Finally, ongoing research is examining the impact of diabetes on quality of life using data gathered
from the Diabetes Control and Complications Trial (DCCT) and the follow-up to the DCCT. Of
particular interest is the relative role of different patterns of complications on shifting quality of life in
diabetic patients. This patient cohort has been carefully characterized and is being followed over an
approximately fifteen-year period on medical, psychological and quality of life indices. Therefore, we
are in a unique position to assess the mechanisms by which diabetes affects patient quality of life.
Contact:
Alan M. Jacobson, M.D.
Clinical Research Training Program Preceptor
Senior Vice President
Strategic Business Initiatives
Joslin Diabetes Center
1 Joslin Place
Boston, MA 02215
Phone: (617) 732-2657
Fax: (617) 732-2487
Email: [email protected]
Psychobiology of Eating Disorders
Preceptor: David C. Jimerson, M.D.
Beth Israel Deaconess Medical Center
This project is directed toward achieving greater understanding of psychosocial and psychobiological
factors contributing to illness onset, symptom perpetuation, treatment response and treatment non-response
in patients with eating disorders. Psychological parameters under investigation as correlates of clinical
course and treatment response include symptoms of depression, anxiety, impulsivity and compulsive
behaviors. Neurobiological factors of interest include central nervous system amine neurotransmitters and
neuropeptides. A central focus of investigation includes follow-up of initial studies suggesting that
decreases in serotonin and neuropeptide function may contribute to impaired satiety responses and binge
eating behaviors in some patients with bulimia nervosa. Additional studies are evaluating whether
serotonin deregulation contributes to impaired response to treatment interventions in anorexia nervosa.
Studies assessing eating patterns and neuroendocrine regulation are conducted on the hospital's General
Clinical Research Center. Collaborative clinical investigations include comparative studies in other
psychiatric disorders showing therapeutic response to antidepressant medications. This multidimensional
project provides a range of research opportunities for interested postdoctoral Fellows.
Contact:
David C. Jimerson, M.D.
Vice Chair for Academics and Research
Department of Psychiatry
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA 02215
Phone: (617) 667-4667
Fax: (617) 667-3225
Email: [email protected]
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Studies of Temperament in Children
Preceptor: Jerome Kagan, Ph.D.
Harvard University, Department of Psychology
This project seeks to understand the developmental course of two temperamental categories of
children called inhibited and uninhibited. A major focus of the work is to trace from early infancy the
predictive validity of signs of limbic arousal that seem to be especially diagnostic of the two
temperamental categories. This sample is being evaluated at 10 years of age.
A second project involves the assessment at 2, 4, and 6 years of age of children whose parents have
been diagnosed with panic disorder and/or depression, along with a control group. This project is a
collaboration with Drs. Rosenbaum and Biederman at Massachusetts General Hospital.
Contact:
Jerome Kagan, Ph.D.
Professor and Chairman,
Department of Psychology
William James Hall
Harvard University
33 Kirkland Street
Cambridge, MA 02138
Phone: (617) 495-3870
Fax: (617) 495-3728
Email: [email protected]
21
Genetic Analysis of Schizophrenia-related Traits
Preceptor: Deborah L. Levy, Ph.D.
McLean Hospital
The role of genetic factors in the etiology of schizophrenia is well-documented, yet finding
a gene for schizophrenia has been elusive, partly because its mode of transmission is not
classically Mendelian. The recurrence risks for schizophrenia in first-degree relatives of
schizophrenics are low (2.5-12%). Since conventional linkage analysis limits "affected" status
to a clinical phenotype, the power of linkage analysis for schizophrenia is low, resulting in an
unacceptably high false negative rate.
The goal of this investigator's research program is to improve the power of linkage studies
by basing affectedness on traits that have a higher genetic "signal" than a clinical phenotype.
Thus, although schizophrenia itself is not highly penetrant, the investigator and her colleagues
have shown that certain traits are correlated with schizophrenia and occur at a higher rate in
relatives of schizophrenics. Prominent among these so-called "enriched" traits, which could
serve as useful pointers to the gene(s) for schizophrenia in linkage analysis, are schizophrenia
spectrum disorders, thought disorder, eye tracking dysfunction, and craniofacial
dysmorphology. The higher prevalence of these schizophrenia-related traits increases the
power to detect a major locus for one or more of these traits, which may, in turn, be associated
with the genetic transmission of schizophrenia. The investigator and her colleagues have
shown that an autosomal dominant gene with pleiotropic effects can account for many features
of the transmission of schizophrenia, eye tracking dysfunction or both. This finding supports
the usefulness of considering linkage to a multidimensional phenotype.
We propose to maximize discrimination among genotypes by mapping these more
prevalent associated quantitative traits, rather than relying on an all-or-none disease
phenotype. We use both nonparametric and model-dependent methods to test for linkage in a
sample comprising 160-208 sibling pair combinations and we include recent modifications of
the Haseman-Elston method as well as lod score analysis. Discriminant functions are used as
quantitative phenotypes. The entire genome is scanned for evidence of linkage to individual
quantitative phenotypes and combinations of quantitative phenotypes by typing highly
informative multi-allele markers, using a map of 10 cM or less. The first stage applies a coarse
screening sieve to identify promising regions for follow-up (a nominal p-value <0.10). In the
second stage, the goal is to detect false positive results from the scan and improve localization
through fine mapping, including haplotype analysis.
Contact:
Deborah Levy, PhD
Clinical Research Training Program Preceptor
Psychology Laboratory
Centre Building
McLean Hospital
115 Mill Street
Belmont, MA 02178
Phone: (617) 855-2854
Fax: (617) 855-2778
Email: [email protected]
22
Relational and Genetic Factors in Trajectories toward Adult Disorder:
Prospective Longitudinal Study From Infancy
Preceptor: Karlen Lyons-Ruth, Ph.D.
Cambridge Hospital
The Biobehavioral Family Studies Laboratory at Cambridge Health
Alliance/Harvard Medical School, under the direction of Dr. K. Lyons-Ruth, has focused
on the assessment of attachment relationships in high-risk environments over the infancy,
childhood, and adolescent periods and has been supported by the National Institute of
Mental Health, the National Institute of Child Health and Human Development, the SmithRichardson Foundation, the Borderline Foundation, the Mailman Foundation, and the
Commonwealth Fund. Under current NIH funding, investigators are developing tools for
assessing attachment relationships in adolescence and evaluating their interplay with
traumatic experiences and genetic factors in contributing to young adult depression,
suicidality, and impulsive self-damaging behavior, in collaboration with the genetics labs
of Dr. Maria Sasvari, Department of Molecular Biology, Semmelwe is University, and Dr.
David Pauls, Department of Psychiatry, Harvard Medical School. Other research in
progress includes examination of stress-hormone responsiveness to interpersonal conflict
among patients with borderline personality disorder with Drs. Gunderson and Zanarini,
McLean Hospital, Harvard Medical School, supported by the FHL Foundation, and
evaluation of fMRI responses in the basal ganglia associated with anhedonia among young
adults with and without histories of early trauma, with Dr. D. Pizzagalli, Department of
Psychology, Harvard University, supported by NIH. Research opportunities exist to
explore a range of longitudinal predictors of adaptation in adolescence among high-risk
youth.
Contact:
Karlen Lyons-Ruth, Ph.D.
Clinical Research Training Program Preceptor
Associate Professor of Psychology
Department of Psychiatry
Cambridge Hospital
1493 Cambridge Street
Cambridge, MA 02139
Phone: (617) 547-3116
Fax: (617) 503-8473
Email: [email protected]
23
Functional Neuroimaging of Cognitive Deficits in Schizophrenia and Autism
Dara S. Manoach, Ph.D.
Massachusetts General Hospital, Charlestown
Cognitive deficits in schizophrenia and autism are profoundly disabling and, at present, effective
treatments are lacking. The goal of our research program is to elucidate the neural bases of cognitive
function in health and in psychopathology. We are particularly interested in the contributions of the
prefrontal and anterior cingulate cortices to executive functions including response monitoring,
inhibition, task-switching, and working memory. We use saccadic eye movements as the platform for
our experiments because they have a well-characterized neuroanatomy and neurophysiology. Because
executive functions are dynamic and continuous, studying their neural basis requires methods with high
spatial and temporal resolution. We combine the spatial precision of event-related functional magnetic
resonance imaging (fMRI) with the high temporal resolution of magneto- and electroencephalography
(MEG/EEG) to derive spatiotemporal movies of brain activity. Because executive functions are the
product of coordinated activity in distributed networks, we use high resolution diffusion tensor imaging
(DTI) to investigate the microstructural integrity of network white matter and fMRI-based functional
connectivity analyses to assess the strength of correlated activation in the regions that comprise these
networks. Finally, since recent work suggests that executive functions are genetically mediated by
common polymorphisms, we are examining the contribution of these polymorphisms to inter-individual
variation in response monitoring in health and psychopathology. Together, these methods can identify
functional and structural correlates of abnormal cognition and its relation to common genetic
polymorphisms. The identification of clinically relevant intermediate phenoypes can guide the search
for genes and mechanisms. In addition, understanding how genotype affects specific manifestations of
these disorders may allow for individualized treatment of targeted behaviors.
A separate line of investigation, conducted in collaboration with Robert Stickgold, Ph.D., focuses on
the role of sleep in cognition. Patients with schizophrenia do not show normal improvements in
memory consolidation after a night of sleep. We are investigating the basis of this failure using
overnight polysomnography and behavioral studies.
There are opportunities for research fellows to use existing datasets to develop and test their own
hypotheses and to contribute to the acquisition new data either as an adjunct to ongoing studies or as part
of a new study. Training in the acquisition, analysis, and interpretation of neuroimaging data will be
provided.
The PI is a neuropsychologist with a longstanding interest in cognitive neuroscience. She is member
of the MGH Psychiatric Neuroimaging Program directed by Randy Buckner, Ph.D. The laboratory is
located at the Athinoula A. Martinos Center for biomedical imaging on the Charlestown campus of
Massachusetts General Hospital.
Contact:
Dara S. Manoach, Ph.D.
Clinical Research Training Program Preceptor
Associate Professor of Psychiatry
Massachusetts General Hospital
Charlestown Navy Yard
149 13th St. Room 2608
Charlestown, MA 02129
Email: [email protected]
Phone: 617-724-6148
Fax: 617-726-4078
24
Laboratory of Neuroscience, VA Schizophrenia Center, Boston CIDAR
Preceptor: Robert W. McCarley, M.D.
Brockton/West Roxbury VA Medical Center
This multi-site laboratory includes both basic neuroscience and clinical research, as reflected in the
interdisciplinary project title,”Schizophrenia: Functional and Structural Studies. “A central focus of the
work is on measures related to the temporal lobe, and the relationship of functional and structural
abnormalities to clinical symptoms. Technologies in use include electrophysiological studies (especially
mismatch, gamma oscillations, P300, N400), structural volumetric MRI measurements, and functional
MRI studies. Subject populations include schizophrenics (prodromes for psychosis, first episode and
chronic patients), and schizotypal personality disorders. A major theme of the project is the application
of basic neuroscience knowledge and techniques to the study of schizophrenia. The four sites
(Cognitive Neuroscience Lab, Brockton VAMC; Brain Imaging Lab, Beth Israel Deaconess; Cognitive
Neuroscience Laboratory, McLean Hospital; Psychiatric Neuroimaging Lab, Brigham and Women’s
Hospital) included within, or affiliated with this laboratory allow recruitment of diverse subject groups,
both diagnostically and demographically. In addition, Dr. McCarley is PI of the Boston CIDAR, a
NIMH program project looking at longitudinal progression of prodromes and first episode schizophrenia
with an extensive biomarker set (electrophysiology, MRI, DTI, fMRI, hormones) that will associated
with genetics to examine genes related to progression (www.bostoncidar.org). The following former
CRTP Fellows are now staff members of this lab or affiliated labs: Drs. Shenton, Wible, Nestor,
Salisbury, Spencer and Niznikiewicz.
Contact:
Robert W. McCarley, M.D.
Professor and Director, Neuroscience Laboratory
Chair, Harvard Department of Psychiatry,
Associate Director, Mental Health,
VA Boston Healthcare, Brockton Campus Psychiatry 116A
940 Belmont St.
Brockton MA 02301
Fax 508 586 0894
Contact Phone: Marie Fairbanks, Harvard Program Administrator 774 826 2479
Kris Pike, Harvard Secretary 774 826 2485
Mary Tarantino, VA Program Assistant 774 826 2473
25
The Study of Child Care as Early Experience
Preceptor: Kathleen McCartney, Ph.D.
Harvard Graduate School of Education
Studies of child care inform theoretical questions concerning early experience and development as
well as social policy questions concerning child care regulation and practice. The NICHD Study of Early
Child Care and Youth Development is a multi-site, prospective, longitudinal study of 1103 children and
their families. Work is organized by five issues: (1) the interplay between early and concurrent
experience and developmental trajectories from birth through middle childhood; (2) the extent to which
different processes account for developmental trajectories across children and/or families that differ with
respect to cultural, social, or economic niche; (3) the ways in which experience in familial and
extrafamilial contexts contribute to risk and resilience; (4) the consequences of work-family relations for
parents' well-being and that of their children; and (5) gene-environment interplay.
Research opportunities exist to study a variety of questions. The data set from the first four phases of
the NICHD study (1 month through 15 years) is public access. The website for the project is:
https://secc.rti.org/. Three of my most recent papers using this dataset include:
McCartney, K., Burchinal, M., Clarke-Stewart, A., Bub, K. L., Owen, M. T., Belsky, J. & NICHD Early
Child Care Research Network. (in press). Testing a series of causal propositions relating time in
child care to children’s externalizing behavior. Developmental Psychology.
McCartney, K. & Berry, D. (in press). Whether the environment matters more for children in poverty. In
McCartney, K. & Weinberg, R. (Eds.) Experience and Development: A Festschrift in Honor of
Sandra Wood Scarr. New York: Taylor & Francis.
Dearing, E., McCartney, K., & Taylor, B. A., (in press). Does higher-quality early child care promote
low-income children’s math and reading achievement in middle childhood? Child Development.
Contact:
Kathleen McCartney, PhD
Clinical Research Training Program Preceptor
Dean and Gerald S. Lesser Professor in Early Childhood Development
Harvard Graduate School of Education
13 Appian Way, Longfellow 101
Cambridge, MA 02138
E: [email protected]
P: 617-495-3401
F: 617-495-8510
26
Longitudinal Investigation in Psychiatric Epidemiology:
The Stirling County Study
Preceptor: Jane M. Murphy, Ph.D.
Massachusetts General Hospital
This project has built a longitudinal data base in order to examine time trends in the distribution and
frequency of psychiatric disorders among 4000 sample members in a general population. The research
site is an area in Atlantic Canada which has been given the fictitious name of ”Stirling County“ for
purposes of protection. Comparative information is provided by cross-sectional studies of an urban site
in the United States and of cross-cultural sites in other parts of the world.
The design of the Stirling Study consists of four repeated cross-sectional surveys and three panel
follow-up investigations. This type of design provides information on time trends through changing or
stable prevalence rates and about the natural history of disorder through information on incidence,
course, and outcome including mortality rates. Psychosocial risk factors are investigated in regard to
associations with epidemiologic rates.
Data have been gathered from subjects through structured interviews. In the current field work,
which brings the study to the 40-year mark, three schedules have been employed. One is an interview
schedule focused on depression and anxiety which was developed for and used consistently throughout
the study, beginning in 1952. Another consists of the depression, anxiety, and alcohol abuse sections of
the Diagnostic Interview Schedule which was developed for NIMH’s Epidemiological Catchment Area
program. The third is the Modified Mini-Mental Status Examination which deals with cognitive
impairment. The latter was selected in light of the fact that aging is the common denominator of the
panel follow-up studies.
All subjects have been asked if they would be willing for a general physician of their naming to be
interviewed about their health. Based on a 90% permission rate, local family physicians have been
interviewed by psychiatrists using a semi-structured format. Drs. Cassem, Cremens, Hegarty, Kurland,
Manschreck, and Teehan participated in this aspect of the study as the psychiatrists who conducted the
interviews with physicians.
27
Information for a validation study has been gathered using the Structured Clinical Interview for
DSM-III-R (SCID). While the SCID will be used as a gold standard for assessing the accuracy of
subject- and physician- identified psychiatric cases, assessment of the SCID itself will also be carried
out. The latter assessments will analyze the agreement between an interviewer and an observer and
between the SCID interview results and the accumulated longitudinal materials. Collaborators in this
aspect of the study were Drs. Levitt, Shenton, Turvey, Vogel, and Worthington.
Contact:
Jane M. Murphy, Ph.D.
Clinical Research Training Program Preceptor
Chief of Psychiatric Epidemiology
Massachusetts General Hospital
Psychiatric Epidemiology Unit
149 13th Street, Suite 9155
Charlestown, MA 02129-2000
Phone: (617) 726-1822
Fax: (617) 724-8301
Email: [email protected]
28
Outcome Research on Psychotherapy for Substance Abuse
Preceptor: Lisa M. Najavits, PhD
Harvard Medical School
This research program focuses on applied clinical research to develop and evaluate psychotherapies
for substance abuse populations, particularly "challenging" populations such as patients with the dual
diagnosis of posttraumatic stress disorder (PTSD) and substance abuse. In addition, a sub-topic is the
study of therapeutic expertise: identification, characteristics, and training of expert therapists. There are
two main projects:
1) The primary focus is the evaluation of a specific psychotherapy treatment, Seeking Safety, for
patients with PTSD and substance abuse. The treatment is cognitive-behavioral (with psychodynamic
influence) and offers 25 topics, summarized in a treatment manual, for integrated treatment of both
disorders at the same time. Existing data from outcome studies on adolescent girls and adult women are
available for analysis and writing. On-going studies include three national multisite studies: a study of
homeless women veterans at ten Veterans Administration hospitals; a three-site study on women,
violence, and substance abuse; and a three-site pilot study combining it with exposure therapy for the
treatment of men. The goal in all of the projects is to adapt the treatment for each of these
sub-populations and to evaluate outcomes (typically compared to "treatment as usual" control samples).
Examples of questions that can be addressed include: identifying what symptomatic and functional areas
change as a result of the treatment; relating therapist adherence to outcome; evaluating patient factors
that predict better and worse outcomes; descriptive papers (e.g., psychometric evaluations of
instruments, and descriptions of the sample), and the development of improved therapist training
methods. All of these studies are funded by NIH or other national funding agencies.
2) The National Institute on Drug Abuse Collaborative Cocaine Psychotherapy Study, which is the
largest psychotherapy outcome trial conducted on cocaine-dependent patients. This study evaluated
three theoretical orientations: cognitive-behavioral, psychodynamic, and 12-step, with over 700 patients
and 60 therapists in the combination of the pilot study and main trial. A variety of secondary analyses
on this data set are possible.
The postdoctoral trainee could work on a variety of areas, depending on interest and experience,
including: data analysis and writing of journal articles, assistance with preparing grant applications,
clinical work (e.g., conducting the protocol treatment), and assisting with supervision on the multi-site
trials. There may also be an opportunity to collect data that might be of interest to the trainee (e.g., on
one of the on-going studies or as part of a new study).
Contact:
Lisa M. Najavits, PhD
Professor of Psychiatry, Boston Univ. School of Medicine
Lecturer, Harvard Medical School
Phone: (617) 731-1501
Fax: (617) 701-1295
[email protected]
Website: www.seekingsafety.org
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The Developmental Medicine Center Laboratory of Cognitive Neuroscience
Preceptor: Charles A. Nelson, PhD
Children’s Hospital Boson
The specific interests of this new site, Directed by Dr. Charles Nelson are concerned with the
effects of early experience on brain and behavioral development, with specific interests in the effects of
early biological or psychosocial adversity. Dr. Nelson’s research program focuses on the development
and neural bases of memory, face and emotion processing, and executive functions. Nelson studies both
typically developing children and children at risk for neurodevelopmental disorders, and employing
behavioral, electrophysiological (ERP), and metabolic (MRI) tools in his research.
Dr. Nelson moved to Harvard in 2005, having previously served on the faculty at the University
of Minnesota. Dr. Nelson chaired the John D. and Catherine T. MacArthur Foundation Research
Network on Early Experience and Brain Development, and served on the National Academy of Sciences
panel that wrote From Neurons to Neighborhoods. Opportunities for CRTP Fellows could include direct
research involvement, supervised by Dr. Nelson, or collaborative projects, which involve Dr. Nelson and
other CRTP faculty. Depending on level of involvement, trainees could learn many of the neuroimaging
tools that currently comprise Dr. Nelson’s armamentarium.
Contact:
Charles A. Nelson III, Ph.D.
Clinical Research Training Program Preceptor
Professor of Pediatrics
Harvard Medical School
Richard David Scott Chair in Pediatric Developmental Medicine Research
Children's Hospital Boston
Developmental Medicine Center Laboratory of Cognitive Neuroscience
1 Autumn Street
Office AU621 Mailbox #713
Boston, MA 02215-5365
Phone (office): (617) 355-0401
Phone (lab): (617) 355-0400
Fax: (617) 730-0518
Email: [email protected]
http://www.childrenshospital.org/research/babybrain
30
Language Systems in Schizophrenia: Behavioral and ERP Data
Preceptor: Margaret Niznikiewicz
Harvard Medical School
The purpose of this research project is to develop a comprehensive model of language dysfunction in
schizophrenia spectrum disorder including chronic schizophrenia, first episode schizophrenia, and
schizotypal personality disorder. In addition, we propose to examine the relationship between clinically
assessed thought disorder (using thought disorder index, TDI) and experimental and neuropsychological,
and electrophysiological (event related potential -ERP) measures of language dysfunction.
Background and significance:
Language dysfunction in schizophrenia has been regarded as a hallmark feature of positive
symptomology in schizophrenia. Numerous studies of the properties of language in schizophrenia
documented the tendency to use the dominant meaning of a work regardless of context (Chapman,
Chapman, and Dant, 1976), poorly organized discourse (Harvey, 1983) and inappropriate use of
pronouns (Harvey, 1983). Clinically, language dysfunction has been described in terms of thought
disorder. Clinical evidence for thought disorder is obtained from semi-structured interviews which
allow to obtain a sample of a patient's speech and score it according to pre-defined categories. More
recently it has been suggested that the language impairment is mediated by dysfunctional processes
within semantic networks (Kwapil et al., 1990; Spitzer et al., 1994; Barch et al., 1999). Furthermore,
recent studies suggested that schizophrenia disease process is not an all-or-nothing process, but may
express itself along the continuum of severity. For example, it has been proposed that both
schizophrenia and schizotypal personality disorder belong to schizophrenia spectrum disorders, and that
individuals carrying a diagnosis of either a schizophrenia or SPD share similarities at several levels of
analysis e.g., 1) neurochemical (Siever et al., 1993) 2) deficits in performance measures of vigilance
(Condray and Stainhauer, 1992) 3) early inhibitory deficits (Perry et al., 1997; Cadenhead et al., 2001)
4) deficits in performance measures of attention and information processing (Kremen et al., 1994;
Trestman et al., 1995) 5) deficits in verbal and working memory (Volgmaier et al., 1997; Park and
McTigue, 1997; Moriarty et al., 2001) 6) eye tracking abnormalities (e.g., Keefe et al., 1989; Siever et
al., 1990; Levy et al., 1994; Clementz et al., 1995; O'Driscoll et al., 1998) 7) event-related potential
abnormalities including P300 and N400 (e.g., Friedman and Squire-Wheeler, 1994; Salisbury et al.,
1996; Niznikiewicz et al., 2000; Niznikiewicz et al., 1997).). In addition, there exists an ongoing debate
regarding the possible progression of severity from the first onset of schizophrenic symptoms to chronic
schizophrenia, with some data suggesting the lack of worsening of symptoms after the first episode
(here, and in many studies, defined as the time of the first hospitalization) (Censits et al., 1997; Gold et
al., 1999) while other studies (importantly this project, these are ERP studies (Mathalon et al., 2000;
O'Donnell et al.,1995; Salisbury et al., unpublished data) suggest the progression of abnormalities as the
illness progresses over time.
Thus, in this project we propose to study language dysfunction along the spectrum of severity and
include first episode schizophrenia patients, chronic schizophrenia patients, schizotypal personality
disorder individuals and their control groups. We propose to apply a heuristic model of language that
views the organization of language in terms of semantic networks which may be identified by three
distinct but interacting components. These components are referred to as: processes, properties and
31
content. Further, we propose to examine the relationship between clinical measure of thought disorder
as assessed with the Thought Disorder Index (TDI) and neurophysiological and experimental measures
of language dysfunction. As a secondary goal, this proposal seeks to delineate differences between men
and women in the three clinical groups. Both behavioral and event-related potential (ERP) data will be
used to provide complementary evidence on both normal and pathological brain processing of language.
Hypothesis:
Our main hypothesis is that language disturbance in SPD and both in FES and CS begins with a
breakdown of semantic network processes related to activation, to inhibition, and to utilization of
context, which in turn leads to semantic aberration, as reflected by abnormal N400 to word pairs and
sentence endings. Gradual breakdown of language system (with least impairment in SPD and the most
severe impairment in CS) is predicted. According to this model, both SPD and schizophrenia are
characterized by abnormalities in the processes and properties of semantic networks, but of differing
degrees. Thus, we predict that different patterns of N400, event-related gamma, and neuropsychological
abnormalities will be found in each of the three clinical samples. Correlational analyses between ERP,
behavioral, neuropsychological, and clinical (thought disorder measures) data sets will help provide
converging evidence on language problems in schizophrenia spectrum disorders.
We propose to test these hypotheses in a five-year study of three schizophrenia spectrum groups: 1) 30
patients with CS and 30 matched normal controls; 2) 30 patients with FES and 30 matched normal
controls; and 3) 30 individuals with SPD and 30 matched normal controls. Each control group will be
matched for age, gender, and parental SES to its respective clinical group and all subjects will be righthanded and have English as their primary language.
Contact:
Margaret Niznikiewicz, Ph.D.
Psychiatrt 116a
Boston VA Medical Center
940 Belmont St.
Brockton, MA
Phone: (508) 583-4500 x2632
Fax: (508) 580-0059
Email: [email protected]
32
The Families and Addiction Program
Preceptor: Timothy J. O’Farrell, Ph.D.
VA Boston Healthcare System
The objectives of the Families and Addiction Program are to conduct research on family treatment
and family processes among individuals with alcoholism and drug problems; and provide training and
clinical services related to this research.
Family treatment research has examined behavioral couples therapy (BCT), a specialized form of
substance abuse counseling developed by O’Farrell and colleagues to support the patent’s abstinence
and improve relationship functioning. Studies by O’Farrell and colleagues show that BCT produces
greater abstinence, happier relationships, fewer separations, and greater reductions in social costs,
domestic violence, and emotional problems of the couple’s children than typical individual-based
treatment. BCT also improves compliance with recovery-related medications, including disulfiram for
alcoholism and naltrexone for alcoholism and for opioid addiction. Virtually all recent reviews of
research on psychosocial treatments for alcoholism and drug abuse cite BCT as an empirically supported
method for treating alcoholism and drug abuse. Other research has shown that brief family meetings
promote aftercare among patients in inpatient detoxification. Ongoing work examines BCT with drugabusing women, opioid patients taking Suboxone, and patients living with a family member other than a
spouse.
Family process research has targeted domestic violence, expressed emotion, and other processes.
Dr. O’Farrell showed for the first time that domestic violence is reduced after treatment for alcoholism;
in fact, violence is almost nonexistent among those alcoholics who remain abstinent after treatment.
These findings led to ongoing research examining the natural history and explanatory models of
domestic violence among men and women with alcoholism. He also showed for the first time that
spouses’ negative expressed emotion (mainly high levels of criticism) predicts subsequent relapse
among alcoholics as it does in schizophrenia, mood and eating disorders. Other work has examined
sexual adjustment among substance abuse patients and functioning of children in these families.
Dr. O’Farrell’s research program, which has been continuously funded since 1978, has produced 4
books and over 250 publications. He has received over 20 grants from VA, NIH, and other sources for
total research funding to date as PI of over 15 million dollars in direct costs. He has provided research
and clinical training to over 60 fellows, over 15 of whom have obtained their own research funding.
Over 25 different fellows have co-authored at least 1 publication with him; and over 90 of his
publications have been co-authored with former fellows.
This training site will be relevant for Fellows interested in addiction studies as well as in interactions
between family processes and psychopathology.
Contact:
Timothy J. O'Farrell, Ph.D.
Clinical Research Training Program Preceptor
Professor of Psychology, Dept. of Psychiatry, Harvard Medical School
VA Boston Healthcare System, 940 Belmont Street, Brockton, MA 02301
Phone: (508) 583-4500 x63493 Fax: (774) 826-1087
Email: [email protected]
33
Psychobiological Research in Posttraumatic Stress Disorder
Preceptor: Scott P. Orr, Ph.D.
Massachusetts General Hospital
Our laboratory has been conducting research on trauma-related psychiatric disorders since 1983 and
is an internationally recognized leader in the psychobiological study of posttraumatic stress disorder
(PTSD). Through grants from the National Institute of Mental Health and Department of Veterans
Affairs our facility provides the latest in state-of-the-art diagnostic interviewing, psychological testing,
and psychophysiological and neuroimaging assessment of PTSD. Previous research from our group has
focused on a range of psychobiological issues related to the long-term effects of combat stress,
childhood sexual abuse, breast cancer, and various other traumatic events such as assault, accidents, and
fires. This work has included examinations of psychophysiological reactivity and PET activation during
trauma-related imagery, measurement of the startle response and conditionability, MRI assessments of
hippocampal volume, electrophysiological studies of cognitive processing, and assessments of the
efficacy of different treatment modalities. Currently funded projects include: a prospective
psychophysiological examination of risk for PTSD in firefighters, police, and emergency workers; brain
volumetric (MRI) and electrophysiological studies of male and female veterans with chronic PTSD; and
an fMRI study of brain activation responses during challenge in combat veterans with and without
PTSD and their twin brothers, who were not exposed to combat.
Contact:
Scott P. Orr, PhD
Clinical Research Training Program Preceptor
Professor of Psychology in the Department of Psychiatry
Contact info for CRTP site doc:
Massachusetts General Hospital
Building 149 - 13th Street
Charlestown, MA 02129
Phone: (617) 726-7817
Email: [email protected]
34
Psychiatric and Neurodevelopmental Genetics Research Unit
David Pauls, Ph.D.
Harvard Medical School
The primary goal of Dr. Pauls’ research is to understand the genetic and environmental mechanisms
involved in the development of mental illness. His work has focused on four different developmental
neuropsychiatric disorders: the Gilles de la Tourette syndrome, obsessive compulsive disorder (OCD),
high functioning autism/Asperger's syndrome and specific reading disability. As noted, the goal of all of
this research has been to understand the etiologic mechanisms that underlie the manifestation of specific
behaviors that begin in childhood and continue over the life course. The research has examined
components of the clinical phenomenology of each of these conditions and their transmission within
families. Over the years the Pauls lab has employed clinical, quantitative and molecular genetic
approaches encompassing family/genetic studies, segregation studies examining the transmission of
specific phenotypes, genetic linkage studies and genome wide association studies designed to localize
and characterize genes that confer susceptibility to these conditions and prospective longitudinal studies
designed to exploit the linkage findings to examine the interactions of identified genes and
environmental factors.
Modern genetic studies of complex behavioral traits have relied primarily on the analysis of
dichotomous phenotypes (i.e., affected/not affected). Over the years it has become increasingly
apparent that traditional methods for classifying individuals as affected/unaffected are inadequate for
genetic studies. Given this shortcoming, the Pauls lab has employed a variety of assessment methods
that address multiple quantitative dimensions of phenotypes of interest that will facilitate the
examination of distinct components of these complex phenotypes and the development of alternative
ways of understanding the inherited phenotype. The Pauls group has employed a more deliberate
approach to symptomatic sub-classifications that employs factor analysis and other analytic approaches
to discern possible underlying phenotypic constructs. As applied to symptomatic phenotypes, factor
analysis extracts information from the full range of available symptom data and reduces it to a small
number of factors that are comprised of a group of non-overlapping symptoms. Hence individuals
(whether they carry a diagnosis or not) are assigned factor scores and those scores can be used as a
phenotype for genetic analyses. Rather than scores based upon affected/not affected or upon the simple
presence/absence of symptoms, factor scores allow an increase in sensitivity by the adjustment of a
dichotomous "threshold score": the subgroups of individuals are adjusted based upon the factor scores.
It has been possible to utilize factor scores as continuous quantitative traits thereby maximizing the
amount of phenotype information for a given sample. Factor scores should provide a means for
addressing the heterogeneity inherent in human genetic disease.
Using a similar approach for disaggregating the phenotype, it was possible to demonstrate linkage
for several loci conferring susceptibility for specific reading disability. This approach has already had a
significant impact on the study of other complex traits. For example, using a similar approach, many
groups have demonstrated that there are at least four separate components that comprise the OCD
phenotype. In a recent study, Dr. Pauls and colleagues demonstrated that some of these components are
heritable. In a two similar studies completed in the Pauls lab with GTS patients and families, the results
suggest that there may also be separate heritable components of GTS.
35
While the primary focus of the work in the Pauls lab to date has been the elucidation of genetic
mechanisms important for the manifestation of complex developmental behavioral disorders, they have
also been interested to learn more about the impact of non-genetic/environmental factors on the
expression of these behaviors and the interaction between genes and environment in the development of
behavior. To accomplish this goal for GTS and OCD, a prospective longitudinal study of children at
risk was undertaken that was designed to identify non-genetic influences associated with the expression
of GTS and OCD in vulnerable individuals and to characterize more carefully the phenotypic expression
of the syndrome. One goal of this study was to assess factors that may influence emerging
developmental capacities, such as pre- and perinatal risk, relational aspects of family functioning and
parental strategies. Preliminary findings from this study suggest that there is considerable variability in
the expression of GTS, OCD and associated behaviors that is in part mediated by non-genetic factors. A
second goal of this study was to characterize more carefully the variable expressivity of the GTS
spectrum. To achieve this goal, it was essential to characterize aspects of development that may impact
the relation between the GTS spectrum and adaptive functioning (e.g., interpersonal relationships,
school performance). Thus, regulation of attention, impulsivity and affect was assessed, as well as
domains of neuropsychological functioning and academic achievement; domains that have been
previously reported to be areas of relative weakness for some children affected with GTS.
This was the first prospective longitudinal study of GTS and OCD. Prospective longitudinal data of
individuals at risk are needed to document the developmental course of these disorders to examine more
adequately the impact of pre- and perinatal risk factors and aspects of family functioning on the
manifestation of the illness.
As noted, the Pauls group is also actively engaged in genetic linkage and association studies of GTS
and OCD. A genome-wide linkage scan completed by the Tourette Syndrome Association International
Consortium for Genetics (TSAICG), of which Dr. Pauls is the chair. A region on the short arm of
chromosome 2 was identified that may harbor susceptibility genes for GTS. This finding was
statistically significant at the genome-wide level. In addition, Dr. Pauls was part of a collaborative
effort to complete a genome-wide linkage scan of OCD. Again, several regions were identified as
possibly harboring susceptibility genes for OCD, but none achieved acceptable statistical significance
levels. At the present time, the Obsessive Compulsive Foundation Genetics Collaborative (of which Dr.
Pauls is also the chair) and the TSAICG are each completing genome-wide association studies on OCD
and GTS respectively. Results from each of these studies should help to narrow the search of
susceptibility genes for each condition. In addition, both consortia have agreed to pool the data for
analysis to examine whether there might be susceptibility genes conferring risk for both disorders.
A closely linked genetic marker or a susceptibility gene can serve as the basis for defining an
appropriate control group for a "genetic case-control" design. These loci can identify quite accurately
those children and siblings who are genetically at risk. Genetically identical individuals constitute an
ideal control group for the identification of non-genetic factors relevant to the onset of illness.
Genetically identical but unaffected siblings have the genetic susceptibility but, since they are not
affected, have presumably not been exposed to the necessary environment risk factors, or may have been
exposed to them at different times in development, or may have encountered protective factors that
resulted in these individuals not manifesting the disorder.
36
In contrast, siblings who are not genetically identical at the relevant loci might very well have
experienced similar environmental risks but be unaffected because they lack the necessary genetic
susceptibility. Comparing probands with their respective genetically identical siblings or children
provides the basis of a genetic case-control paradigm. The ability to utilize data from the human
genome and other aspects of genetic studies to design and carry out a study of non-genetic etiologic
factors of a psychiatric illness is a significant methodological advancement that has not been possible
heretofore. Data from prospective studies will make it possible to examine individuals with specific
genotypes to determine which factors protect some from manifesting the syndrome.
The genome has been sequenced. The speed with which new genes have been characterized has
increased significantly. Determining the function of genes that are important for the manifestation of
behavior will require studies designed to examine the effect of specific environments on the expression
of specific allelic variants. It is highly likely that the most effective research strategies necessary to
achieve these goals have yet to be developed. These new strategies will need to include creative ways of
understanding behavioral phenotypes since the current nosological systems appear to be inadequate in
the search for genes. Furthermore, it will be necessary to develop new methods for measuring aspects of
the environment. Accurate measurement of the inherited phenotype and the relevant environments will
be critical for the elucidation of gene-environment interactions that may be important in the
manifestation of these complex phenotypes. While new paradigms will need to be developed, the
research questions will still focus on what components of the phenotype in question are inherited and
what environmental factors are important in modifying and interacting with the products of those genes.
David L. Pauls, Ph.D.
Professor of Psychiatry (Genetics)
Harvard Medical School
Director
Psychiatric and Neurodevelopmental Genetics Unit Center for Human Genetic Research Massachusetts
General Hospital
185 Cambridge Street
Boston, MA 02114
Phone: (617) 726-0793
Fax: (617) 726-0830
37
Human and Mouse Genetic and Neurobehavioral Studies of Psychiatric Illness
Preceptor: Tracey L. Petryshen, Ph.D.
MGH Main (Boston) / Broad Institute (Cambridge)
Dr. Petryshen is faculty in the Psychiatric and Neurodevelopmental Genetics Unit in the Center for Human
Genetic Research at MGH. She directs the Genetics Core of the Boston CIDAR, a NIMH-funded program
project. She is also Director of the Behavioral Neurogenetics Program in the Stanley Center for Psychiatric
Research at the Broad Institute. Her multi-site laboratory conducts both basic human and mouse genetic
research, and mouse neurobehavioral research.
Human genetic studies in the laboratory are examining the genetic contribution to progressive functional
deterioration in schizophrenia as part of the Boston CIDAR project (www.bostoncidar.org), in collaboration
with Drs. McCarley, Shenton, Seidman, and Goldstein. Schizophrenia subjects across prodromal, first
episode and chronic stages are undergoing electrophysiological, structural and functional imaging,
neurocognitive, and hormonal measurements for genetic association analyses to delineate the genetic
contribution to progressive changes across disease. Training opportunities exist for individuals interested in
genetic association analyses of schizophrenia incorporating single nucleotide polymorphism genotyping,
copy number variation detection, and quantitative analytical methods.
Mouse behavioral genetic research in the laboratory centers on examining psychiatric genes identified in
patient studies and candidate genes implicated in disease endophenotypes (intermediate phenotypes) that are
impaired in psychiatric disorders. Mouse neurobehavioral studies investigate the therapeutic mechanism of
lithium and other mood stabilizers, as well as efficacy of novel drugs targeting pathways implicated in mood
disorders. Technologies and approaches in use include mouse behavioral models of psychiatric symptoms
and endophenotypes, RNA interference and genetic mouse models, biochemical and histological analysis,
and magnetic resonance imaging of mouse brain. Training opportunities exist for individuals interested in
using rodent neurobehavioral models to study the genetic and neural pathways underlying bipolar disorder
and schizophrenia.
Contact:
Tracey L. Petryshen, Ph.D.
Department of Psychiatry, HMS, MGH
Center for Human Genetic Research
185 Cambridge Street, Room 6260
Boston, MA 02114
E-mail: [email protected]
Website: http://www2.massgeneral.org/chgr/faculty_petryshen.htm
38
Biological Psychiatry Research Laboratory
Harrison G. Pope, Jr., MD
McLean Hospital
The Biological Psychiatry Laboratory is primarily involved in a variety of studies of the epidemiology
and clinical features of various forms of substance abuse. Among recent studies underway in the
laboratory are a number of investigations of marijuana, including a large study of the
neuropsychological effects of long-term marijuana use, imaging studies using fMRI in long-term
marijuana users and controls, and in studies of withdrawal symptoms experienced by individuals who
have abruptly stopped smoking marijuana. We are also conducting numerous studies of drug abuse in
athletes, including a study of the long-term medical effects of steroids in former champion bodybuilders
who have now reached middle age, studies of abuse of other "ergogenic" (performance-enhancing)
drugs by athletes of both sexes, studies of opiate abuse among anabolic steroid users; and studies of the
use of "supplements" such as creatine, androstenedione, and ephedrine among young adults. As an
outgrowth of the studies of drug abuse in athletes, we have conducted several recent studies
investigating issues of body image disorders in boys and men, including the development of a novel
computerized instrument, the "somatomorphic matrix," for evaluating body image perception in various
male populations. A female version of the somatomorphic matrix has now also been developed and is
entering field testing. We have also conducted recent studies of eating disorders among men, and of a
questionnaire designed to assess body image pathology in men of various age groups. We have also
recently investigated the epidemiology of methylenedioxymethamphetamine (MDMA or "ecstasy") use
and its relation to high-risk long-term neuropsychologial effects of alcohol consumption and of peyote
(hallucinogen) used among Native Americans in the Southwest. In addition to the studies of substance
abuse, we are also conducting a large family study of psychiatric disorders in Innsbruck, Austria, various
industry-sponsored studies of novel drugs for the treatment of depression and anxiety disorders, and
studies bearing on the controversy surrounding the validity of the dissociative disorders, such as a
dissociative amnesia and dissociative identity disorder.
Contact:
Harrison G. Pope, Jr., M.D., Chief
Clinical Research Training Program Preceptor
Biological Psychiatry Research Laboratory and Professor of Psychiatry Harvard Medical
School/McLean Hospital
115 Mill Street
Belmont, MA 02478
Phone: (617) 855-2911
Fax: (617) 855-3585
Email: [email protected]
39
McLean Hospital Affective Neuroscience (Neuroimaging) Research Laboratory
Scott L. Rauch M.D.
McLean Hospital
Summary: The Affective Neuroscience Research Laboratory at McLean Hospital is located within
the Neuroimaging Center on the Belmont Campus. Under the leadership of Dr. Rauch, the laboratory is
focused on understanding the brain basis of normal affective functions as well as mood, anxiety, and
obsessive-compulsive disorders. The principal modes of inquiry include a full range of magnetic
resonance imaging modalities, as well as cognitive and behavioral neuroscience methods. Collaborative
work bridges to animal research as well as human imaging. Current funding includes federal support for
a large-scale study of anxiety disorders (PTSD, panic, and phobias) with MRI, as well as donorsupported research in collaboration with MGH focusing on OCD. The OCD research involves a
longitudinal study of children and families using MRI as well as genetic methods.
Currently there are 3 junior faculty members and 1 RA working in the laboratory; over the past 20
years, Dr. Rauch has as an extensive record of mentoring fellows in the CRTP program, as well as via
other post-doctoral fellowship mechanisms.
Contact:
Scott L. Rauch, MD
Chair, Partners Psychiatry & Mental Health,
President & Psychiatrist-in-Chief, McLean Hospital
115 Mill St, Belmont, MA 02478
Phone: 617-855-2201
Email: [email protected]
Asst. Sue Riley -- [email protected]
40
Brain Activity and Language Comprehension in Psychosis
Dean F. Salisbury, PhD
Cognitive Neuroscience Laboratory, McLean Hospital
Thought disorder is a cardinal symptom in schizophrenia, and is inferred through abnormal
language. Such thought disorder in schizophrenia is the defining symptom, the sine qua non. The main
problem is in the way that the brain associates concepts. The underlying cognitive dysfunction which
causes thought disorder is unknown. The broad aim of this proposal is to understand the
neurophysiological basis of thought disorder in schizophrenia through the use of event-related potentials
and clinical scales. There are two memory systems related to thinking and symbolic representation.
Semantic memory is a low level system that activates associates whenever you think of something or
read the word. This is automatic and driven by the stimulus. This operates on a word to word basis, not
keeping track of what has gone before. This low level system is modulated by a higher-order memory
system referred to as verbal working memory. This executive system extracts context out of passages
and uses it to order though based on the gist of things. The issue is whether schizophrenia reflects a
problem in the semantic low-level system, such that things get over-activated and crowd the mind, or
whether there is a problem in the executive verbal memory system and context is not utilized properly.
The studies examine the neural basis of language-based associative processes in schizophrenia by
recording the brain’s electrical activity as subjects make decisions about homographs. Homographs are a
class of words which have multiple, unrelated meanings but are spelled and pronounced the same way;
for example, board may mean plank or committee. Homographs are a subset of homophones, spoken
words which sound the same, but may be written differently. Homographs offer a unique tool in
examining the associative intrusions in schizophrenia, since the excitatory spread of activation appears
to select strong a priori meanings of homographs (e.g., board means plank) regardless of contextual cues
which may indicate the weaker meaning of the homograph as more appropriate (e.g., board means
committee). Homographs likely reflect points where the train of thought gets lost in schizophrenia. For
example, John Nash (A beautiful mind) had a delusion where he was paranoid of men wearing red
neckties. He made the association between red ties and communist leanings. If one thinks about it, it's
likely that nearly half of the words in spoken English are homophones, so being able to select the right
meaning based on the context is extremely important. One can understand how disordered thought can
get if that process is aberrant.
41
We use homographs to try to detect whether there is a semantic or executive memory problem or
both in schizophrenia. Manipulation of the homograph meaning selected and the strength of the
association between that meaning and the contextual cues allows for the examination of behavioral (i.e.,
reaction time, subjective judgements of sensibility) and neural (electrical) responses in schizophrenia
versus psychotic mania and normal controls. Context is manipulated by varying the ‘cloze’ probability
of sentence endings, or the probability of that particular ending occurring, for sentences and associative
strength for word pairs and word triplets. Stimuli are presented at fast presentation rates to emphasize
automatic semantic activation processes before executive verbal working memory systems can use
context to inhibit the initial activation. In another condition, slow presentation rates are used to
emphasize maintenance and utilization of context in verbal working memory. As well, we manipulate
the strength of biasing context to observe word-to-word and thematic processes in schizophrenia. The
response and event-related potential measures provide knowledge about the abnormal semantic
processing in schizophrenia, as well as the underlying neural mechanisms responsible for it.
Contact:
Dean F. Salisbury, PhD.
Clinical Research Training Program Preceptor
Harvard Medical School/ McLean Hospital
Cognitive Neuroscience Laboratory
NBG21
115 Mill Street
Belmont MA 02478
Phone: (617) 855-3786
Fax: (617) 855-3795
Email: [email protected]
42
Laboratory of Clinical Neuroscience and Developmental Neuropsychology
Preceptor: Larry J. Seidman, Ph.D.
Massachusetts Mental Health Center (MMHC) Public Psychiatry Division of Beth Israel Deaconess
Medical Center (BIDMC) and Massachusetts General Hospital (MGH) and Commonwealth Research
Center (CRC)
This site supports research into neurodevelopmental disorders, integrating neurocognitive, genetic,
functional and structural MRI, and psychosocial perspectives. The research program has clinical sites at
the BIDMC, MMHC and MGH Clinical and Research Program in Pediatric Psychopharmacology, and a
neuroimaging program at the MGH Martinos MRI Center (at the Psychiatric Neuroscience Program and
the Center for Morphometric Analysis). The major focus is on psychotic illnesses (especially
schizophrenia) and attention-deficit/hyperactivity disorder. A central interest is on the adolescent period
and understanding the neurobiology of transition into psychosis. This is also reflected in studies aimed
at early intervention and prevention of psychotic disorders carried out through the CRC, including the
prodrome to psychosis. Other disorders currently being studied in collaboration with Harvard
investigators include schizotypal personality, and bipolar disorder. Dr. Seidman collaborates closely
with Drs. Biederman, Goldstein, Keshavan, Makris, McCarley, and Shenton.
Contact:
Larry J. Seidman, Ph.D.
Clinical Research Training Program Preceptor
Director, Commonwealth Research Center
Beth Israel Deaconess Medical Center
401 Park Drive, 2 East
Boston, MA 02215
Home Phone: 617-739-5172
Fax: 617-998-5007
Work Phone: 617-998-5039
Email: [email protected]
43
Director, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital,
Harvard Medical School, and Director of the Clinical Neuroscience Division,
Laboratory of Neuroscience, VA Boston Healthcare System,
Brockton Division, Brockton and Harvard Medical School
Co-Director and Preceptor: Martha E. Shenton, Ph.D.
Dr. Shenton is founder and Director of Psychiatry Neuroimaging Laboratory, Department of
Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, and Director of the Clinical
Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare
System, and Harvard Medical School. She is engaged in a number of ongoing projects evaluating brain
abnormalities in schizophrenic patients, first episode patients, schizotypal personality disordered
subjects, post-traumatic stress disorder, William’s syndrome, traumatic brain injury, and other
neuropsychiatric disorders. She is an independent investigator who has close collaborations with Drs.
McCarley, Holzman, Deutsch, Seidman, and Goldstein. The central focus of her work is investigating
links between brain function and structure, and cognitive and behavioral correlates of schizophrenia.
There are rich opportunities for training and many ongoing projects for postdoctoral clinical research
fellows who have an interest in schizophrenia research and in learning how to evaluate structural brain
abnormalities in schizophrenia. Jason Schneiderman, Ph.D. is a recent CRTP Fellow who is working
with Dr. Shenton in investigating clinical, cognitive, and structural abnormalities in patients with a first
episode of schizophrenia and in subjects identified as being at high risk for schizophrenia.
Contact:
Martha E. Shenton, Ph.D.
Co-Director and Preceptor of the Clinical Research Training Program
Department of Psychiatry and Radiology
Brigham and Women’s Hospital
Harvard Medical School
1249 Boylston Street
Boston, MA 02215
Phone: (617) 525-6117
Fax: (617) 525-6150
Email: [email protected]
Website: http://pnl.bwh.harvard.edu
44
The Psychiatric Genetics Program in Mood in Anxiety Disorders
Preceptor: Jordan Smoller, M.D.
Massachusetts General Hospital
Dr. Smoller is a faculty member of Psychiatric Neurodevelopmental Genetics Unit (PNGU)
within the MGH Center for Human Genetic Research (CHGR). He is also Director of the Psychiatric
Genetics Program in Mood and Anxiety Disorders within the MGH Department of Psychiatry. The
CHGR, directed by James Gusella, occupies 60,000 square feet of laboratory, office and clinical
phenotyping space in the new Simches Research Building on the main MGH campus. The MGH CHGR
is a multidisciplinary cross-departmental center that has as its central mission the facilitation of the
genetic research cycle: definition of phenotypic variation in patient populations -> isolation of genes
underlying the phenotypic variation -> characterization in humans and model systems of the
mechanisms that lead from genotype to phenotype -> use of these findings to provide better diagnostic
capacity, disease management and effective treatments to the patient population. The CHGR houses
resident faculty who are expert at different stages of the genetic research cycle, including laboratorybased, analytic and clinical researchers.
The inaugural resident members of the CHGR represent the Departments of Medicine,
Neurology, Pediatrics and Psychiatry and are currently subdivided into three functional units, the
Laboratory of Human Genetic Variation (David Altshuler), the Molecular Neurogenetics Unit (James
Gusella, Marcy MacDonald, Vijaya Ramesh, Susan Slaugenhaupt, Katherine Sims, Vanessa Wheeler,
Naoto Ito), and the Psychiatric and Neurodevelopmental Genetics Unit (David Pauls, Pamela Sklar,
Jordan Smoller, Susan Santangelo, Shaun Purcell) and several other full time faculty including Vamsi
Mootha, Andrew Chess and Mark Daly. The CHGR has close ties and collaborative interactions with the
Broad Institute and the Harvard-Partners Center for Genetics and Genomics.
The Psychiatric and Neurodevelopmental Genetics Unit (PNGU) is housed in the Simches
Research Building and McLean Hospital, Belmont, MA and is comprised of approximately 6,000 square
feet of research space, including both clinical research space (1,600 sq ft at MGH, 400 sq ft at McLean
Hospital) and molecular genetics research space (4,000 sq ft at MGH). The laboratory has approximately
4,000 square feet. Dr. Smoller’s PNGU office is located on the 6th floor of the Simches Research
Building.
The Psychiatric Genetics Program in Mood in Anxiety Disorders (PGPMAD), directed by Dr.
Smoller, conducts epidemiologic, clinical, and molecular genetic research related to mood and anxiety
disorders. Staff and affiliated personnel include psychiatrists, a genetic counselor, social worker,
research assistants and a laboratory technician. The program staff, including Dr. Smoller, have
computer-equipped offices on the 2nd Floor of the Simches Research Building.
45
Specialized genotyping and sequencing facilities: Genotyping is performed by MassARRAY
system (Sequenom, La Jolla, CA). Computer systems: There are approximately 400 square feet
dedicated to servers in a separate locked room adjacent to the molecular genetics laboratory.
This server facility has 4 Sun Sparc Systems running Solaris. These servers include 2 Sun Fire
V480, dual processor units with 20 GB RAM memory. One server hosts our genotypic and phenotypic
database running ORACLE9i. The second hosts a full suite of genetic and statistical applications served
to the PNGU community of researchers directly or via X windows applications to PCs.
Contact:
Jordan Smoller, MD, ScD
Massachusetts General Hospital
Simches Research Building
185 Cambridge Street, 2nd Floor
Boston, MA 02114
Phone: 617.724.0835
Fax: 617.643.3080
Email: [email protected]
46
Individual Differences in Infant Temperament and its Effects on Physiological and Behavioral Measures
of Coping and Memory for Social Stress
Preceptor: Nancy Snidman, Ph.D.
Child Development Unit
Children’s Hospital, Boston
This program, directed by Dr. Snidman and Dr. Edward Tronick, is investigating the relative stability of
individual differences and age-related changes in infants’ (ages 3 months to 12 months) social emotional
and self-regulatory behavior and physiologic reactivity to a social stress, the maternal still-face (SF)
during the Face-to-face Still Face paradigm (FFSF). The FFSF was chosen as the stimulus because it
exposes infants to a unique social-emotional stressor (maternal SF) that differs from inanimate stressors
and elicits well-documented emotional reactions and stress in infants. In addition, the study is
investigating whether differences in infants’ behavioral and physiologic reactivity to the SF at the first
exposure are associated with their memory for the SF at a second exposure.
Prior longitudinal studies by Dr. Snidman focusing on infant temperament and reactivity have revealed
that individual differences in behavioral reactions to environmental stimuli are related to responses in
physiologic systems and can be assessed with peripheral non-invasive measures including heart rate,
respiration, blood pressure, pupil dilation, skin temperature and EEG activity. In one study four month
old infants are given a temperament battery in addition to the FFSF. The temperament battery consists of
presenting to the infant a series of auditory and visual stimuli that are intended to increase in intensity.
For example, a series of three different mobiles are swung in front of the seated infant. The number of
figures on the mobiles increases with each presentation. Some infants respond to the increasingly
complex stimuli with increased motor activity and negative vocalizations. In the FFSF these infants are
compared to infants who do not become more reactive to the stimuli in the temperament battery.
Behavioral measures include motor activity, vocalizations and facial affect. Physiologic measures
include cardiac parameters of both mother and infant as well as infant salivary cortisol and skin
conductance.
Dr. Snidman collaborates with several other investigators in the Boston area who are also interested in
developmental research including Dr. Chuck Nelson from the Laboratory of Cognitive Neuroscience at
Children’s Hospital and Dr. Jerome Kagan from Harvard University Psychology Department.
Contact:
Nancy Snidman, Ph.D.
Director of Research
Child Development Unit, Children's Hospital
1295 Boylston Street, Suite 320
Boston, MA 02115
Ph: 857-218-4370
FAX: 617-730-0074
Email:[email protected]
47
Adolescent Literacy
Preceptor: Catherine E. Snow, Ph.D.
Harvard Graduate School of Education
The Adolescent Literacy Projects at the Harvard Graduate School of Education encompass an array
of studies focused on the vexing issue of underachievement in literacy and academic progress for
students attending urban schools. All of the studies are carried out in the context of the Strategic
Education Research Partnership (SERP; see www.serpinstitute.org), and in particular its field site in the
Boston Public Schools. SERP work requires establishing a long-standing partnership between
practitioners and researchers, so that the researchers can focus their attention on problems nominated by
practitioners as urgently in need of attention. In the Boston site, those problems are primarily related to
middle grades literacy. Various specific efforts being undertaken by SERP researchers working in
Boston include the development and evaluation of an integrated vocabulary curriculum, the adaptation
of that curriculum to the needs of English Language Learners, the development of assessments of
vocabulary depth, oral classroom discourse, and writing to measure the impact of the curriculum,
developing diagnostic literacy tools for use in placing students in interventions, and both developing and
evaluating interventions for delayed readers. Researchers collaborating on the Adolescent Literacy
Projects include Lowry Hemphill, James Kim, and Claire White.
Contact:
Catherine E. Snow, PhD
Clinical Research Training Program Preceptor
Patricia Albjerg Graham Professor of Education
Harvard Graduate School of Education
Larsen 3
Cambridge, MA 02138
Phone: (617) 495-3563
Fax: (617) 495-5771
Email: [email protected]
[email protected]
48
Neural Dynamics Laboratory
Dept. of Psychiatry, Harvard Medical School
Preceptor: Kevin M. Spencer, Ph.D
Research Service, VA Boston Healthcare System
The mission of the Neural Dynamics Laboratory is to understand the relationships between the dynamics
of neural systems and cognitive processes, in healthy people and in individuals with neuropsychiatric
disorders. Currently our focus is on the oscillatory brain dynamics involved in sensory processing,
perception, and selective attention, and the abnormalities of these dynamics in schizophrenia.
Schizophrenia is characterized by various types of brain abnormalities, including neural microcircuitry.
Our hypothesis is that these microcircuitry abnormalities are manifested functionally in EEG
oscillations, and are the basis for particular symptoms and dysfunctional cognitive processes. In our
work we employ high-density EEG recordings and computational modeling. By studying neural
dynamics in healthy and schizophrenic individuals with these methods, we hope to gain insight into both
the neural substrates of “normal” cognition, and the neural abnormalities that are the basis of
schizophrenia.
Kevin M. Spencer, Ph.D.
Director, Neural Dynamics Laboratory
Research Service, VA Boston Healthcare System and Dept. of Psychiatry,
Harvard Medical School
VA Boston Healthcare System
Research 151C
150 S. Huntington Ave.
Boston, MA 02130
Phone: 857-364-4630
Email: [email protected]
49
Child Development Unit
Preceptor: Ed Tronick, Ph.D.
Children's Hospital
The Child Development Unit is directed by E.Tronick, Ph.D. The Unit's goal is to understand the
process of normal child development in low and high risk children and their families. The Unit is
composed of several integrated educational, research and clinical programs: The Touchpoints Project;
directed by T. Berry Brazelton and Josh Sparrow and several NIH sponsored longitudinal research
projects directed by Drs. Nancy Snidman and Marjorie Beeghly. There also are 2 post doctoral fellows
and 3 graduate students in the Unit.

Social Emotional Development in Infants and Children of Mothers with Psychiatric Disorders: Our
research, conducted both in the home and in the lab, studies the effects of maternal psychiatric
disorders including depression, panic disorder and OCD on parental emotions, parenting behavior
and self-reported psychological functioning, and on the development of the children's emotions, selfregulation, attachment, empathy and play from infancy through 5 years of age. Observational data is
coded from video tapes with several different micro and macro systems.

Intervention with High Risk Children and Their Families: The Touchpoints Project is an outgrowth
of Dr. T. Berry Brazelton's recently published book and video series, Touchpoints, in which he
outlines a map of normal development in young children from birth to five years of age. The
Touchpoints Project trains professionals and non-professionals to effectively intervene with high risk
children and their families, and evaluates the effects of the training on the trainees and the families.

Risk and Protective Factors Affecting the Development of a Low Risk Sample of African American
Children: A longitudinal study beginning in infancy and continuing over the first 5 years of life of
the social emotional development of a low risk sample of African American children and the factors
that affect their development.

Motor and Attentional Development in Very Low Birthweight Infants: A study of motor
development using clinical and kinematic assessments, serial ultrasound and magnetic resonance
imaging, and laboratory studies of joint attention of VLBW infants aimed at evaluating the effects of
neonatal lesions and brain plasticity.

Memory for a Social Stress in Infants: A study of memory for the still-face in young infants
exploring the age at which memory for the experience of the still-face begins and how age of
exposure is related to memory duration. The study uses behavior, vagal tone, skin conductance and
cortisol to evalutate infant memory.

Relational Psychophysiology: This study, begun by a former fellow in the program simultaneously
measures the reactivity of the sympathetic and parasympathetic nervous systems in infants and
mothers during normal and stressful interactions. We are exploring the relations among their
physiologies and how maternal psychophysilogic organization affects infants’ physiologic
organization.
50
Contact:
Ed Tronick, PhD
Clinical Research Training Program Preceptor
Chief, Child Development Unit
Children's Hospital
Associate Professor of Pediatrics
Harvard Medical School
1295 Boylston Street, Suite 320
Boston, MA 02215
Phone: (857) 218-4360
Fax: (617) 730-0074
Email: [email protected]
Alternate contact:
Betty Woo 617-355-6948
[email protected]
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The Study of Adult Development
Preceptor: Robert J. Waldinger, M.D.
Brigham and Women’s Hospital
The Laboratory of Adult Development houses two primary studies: the Study of
Adult Development, a 67-year longitudinal study of male psychological and physical
health, and the Close Relationships Project, a study of the effects of family violence in
intimate adult relationships.
The Study of Adult Development involves prospective studies of 268 Harvard
College sophomores and 456 inner-city Boston school boys. Each has lasted for more
than 65 years with minimal attrition. Data for each subject consists of four-generation
social histories, biennial questionnaires, face to face interviews every 15 years, and
complete physical examinations every five years. Research has focused upon 1)
adaptation to stress, mental health, and defense mechanisms; 2) the effects of habits
(especially alcoholism) and affective disorders upon physical health and mortality; 3) the
effect of childhood risk factors upon adult adaptation; 4) the unfolding of adult
development; and 5) the natural history of alcohol and substance abuse. Other ongoing
projects that have evolved from these longitudinal archives include long-term outcome
studies of World War II PTSD, effects of attributional style on physical health, and
successful adult careers by the mildly retarded. We are currently involved in a 5-year
study of the intimate relationships of these men, examining links between the quality of
late life relationships and physical and emotional well-being, along with longitudinal
predictors of late-life relationship functioning. We also contemplate adding genetic,
neuropsychological, and neuroimaging assessments to examine social and biological
determinants of successful aging.
The Close Relationships Project is a study of emotion regulation and intimacy in 109
couples. Many participants have histories of sexual and physical abuse in childhood, and
more than half the couples have histories of recent intimate partner violence. Marital
interactions, video recall techniques, and psychophysiology are among the measures used
to compare relationship functioning in couples with and without histories of family
violence. Variables of interest include emotion experience and expression, empathy,
attachment, and autonomic regulation of arousal.
Contact:
Robert J. Waldinger, M.D.
Department of Psychiatry
Brigham & Women's Hospital
1249 Boylston Street, 3rd floor
Boston, MA 02215
Phone: (617) 525-6133
Email: [email protected]
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Youth Treatment and Intervention Projects
Preceptor: John R. Weisz, PhD
Judge Baker Children's Center
Project 1:
Child System and Treatment Enhancement Projects [Child STEPS]
In youth mental health care, the gap between science and practice is wide and longstanding. Innovative treatments that have been shown to work in clinical trials tend to be
used only in additional clinical trials, not in clinical practice. This network and its
projects are directed toward bridging the science-practice gap and bringing beneficial
treatment practices to youths in mental health service settings. The Clinic Treatment
Project tests two alternative methods of delivering evidence-based practices within
public community-based mental health clinics, using training and supervision procedures
designed for the settings and users. The Clinic Systems Project investigates the
organizational, system, and payment issues that influence the ability of providers and
clinics across the nation to use evidence-based practices.
The Clinic Treatment Project focuses on ethnically diverse youths aged 8-13 who are
referred to community-based mental health clinics in the Boston area and in Honolulu for
conduct problems depression, anxiety, or any combination of these. The youths are
randomly assigned to be treated either with the standard treatment procedures used (usual
care, or UC) in their clinics or with evidence-based practices that have been identified
through our review of the treatment outcome research literature. These evidence-based
psychotherapy practices are trained and tested in two forms: (a) standard manual
treatment (SMT), using full treatment manuals, implemented one at a time, exactly as
they have been tested in clinical trials, and (b) modular manual treatment (MMT) in
which therapists learn all the component practices of the standard manuals but
individualize the use of the components for each child using a guiding clinical algorithm.
Unlike the SMT approach, the MMT approach allows the duration and sequencing of
techniques to be matched to the child’s needs and allows the clinician to draw techniques
from outside the target disorder domain when needed (e.g., to address noncompliance
during the course of treating depression). Assessments are carried out at pre-treatment,
immediate post-treatment, and at 6-months post-treatment.
The Clinic Systems Project examines components of mental health service systems in
200 clinics nation-wide that are expected to impact the adoption, implementation, and
effectiveness of evidence-based practices in community clinics. These components
include: (1) governance structures within and across service sectors (e.g., mental health,
child welfare, juvenile justice, education, health) and the formal and informal linkages
between these structures; (2) service financing structures and reimbursement
mechanisms; and (3) service provider organizations (in this project, mental health
clinics).
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Project 2: Child STEPS Clinic Treatment Project—Maine [CTP—Maine]
The Child STEPs Clinic Treatment Project—Maine is an extension of the Child STEPs Clinic Treatment
Project (described above). The Clinic Treatment Project—Maine examines the impact of clinicians’ use
of modular cognitive behavioral interventions on youth presenting for treatment in community mental
health centers in various cities in Maine. The Clinic Treatment Project—Maine focuses on youths aged
8-13 who are referred for services in community-based mental health clinics in various cities in Maine
for conduct problems depression, anxiety, posttraumatic stress, or any combination of these. All
participating youth have a history of involvement in the child welfare system.
The youths are randomly assigned to be treated either with the standard treatment procedures used
(usual care, or UC) in their clinics or with a modular manual treatment (MMT) version of evidencebased practice, in which therapists learn all the component practices of standard cognitive behavioral
therapy manuals, but individualize the use of the components for each child using a guiding clinical
algorithm. Assessments are carried out at pretreatment and at immediate post treatment. Additionally, in
their first year of participation, participants complete assessments every 3-months. In their second year
of participation, participants complete assessments at 6-month, 12-month, and 24-month follow-up (24months after pretreatment) time points. Assessments include measures of individual youth problems and
disorders, youth and parent perceptions of treatment satisfaction, school achievement and behavior, and
quality and ongoing use of additional mental health services.
Project 3:
Teaching Middle-School Youth Coping Skills for Depression: A School-Based
Intervention Study
Youth depression is a serious condition that causes genuine impairment and is an archenemy of school
performance. It undermines concentration on class work, saps the energy and motivation needed to do
homework, causes significant school absenteeism, and threatens the social connections boys and girls
need for emotional well-being. Rates of depression increase sharply following puberty, highlighting the
public health significance of treatment in early adolescence. Thus, the middle school years may be an
ideal time to help boys and girls build coping skills to ward off depression.
Our long-term goal is to develop and refine treatment for youth depression that is effective and
deployable in a variety of youth settings. In the current study, we focus on the setting in which evidence
suggests the majority of everyday youth mental health care occurs: the school. Efforts to disseminate
empirically supported therapies (ESTs) to schools have not been very successful to date, perhaps for at
least 2 reasons:
1. The design of most EST programs may make them difficult for school counseling personnel to
learn and use, and the design of most programs places a heavy burden on the counselors in terms
of preparation and engagement of children., and
2. EST programs have not yet been shown to outperform current school-based interventions, so
there is not yet a compelling logical case for change.
In this project, we address both potential problems. To address the user appeal issue, we have drawn
from the literature on robust design to restructure our own program—Primary and Secondary Control
Enhancement Training (PASCET) as a video-guided treatment program. The program is designed to be
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efficient and engaging; it teaches coping skills through the use of videotaped vignettes and group
discussion. Through the tapes, youngsters learn nine coping skills that can be used to gain control of
their mood when stressful events make them feel sad or upset. In each of the twelve group sessions, coleaders play video clips and pause periodically to lead group discussion.
To address the case for change issue, we are carrying out a trial of our video-guided treatment with a
commonly used school-based treatment approach as the comparison condition. In this clinical trial, 6th
and 7th graders who show significant levels of depressive symptoms and those who meet criteria for a
depressive disorder are randomly assigned to the two conditions (PASCET or Counselor Intervention),
matched for group format and treatment dose. All treatment takes place in middle schools (in Boston,
Newton, Los Angeles, and Santa Monica). We assess levels of depression and other outcomes
immediately after the end of treatment, and again at a one-year follow-up, to assess the long-term
holding power of the effects.
Contact:
John R. Weisz, PhD, ABPP
President and CEO
Judge Baker Children's Center
53 Parker Hill Avenue
Boston, MA 02120
Phone: (617) 278-4299
Fax: (617) 730-5440
Email: [email protected]
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FMRI Neuroscience of Schizophrenia Laboratory
Preceptor: Cynthia G. Wible, PhD
Brockton VA Medical Center
Cynthia Wible, an Assistant Professor at Harvard Medical School, directs this laboratory
that is based in a Brigham Research Building; she is a former CRTP fellow. Her
doctoral background is in single unit recording studies in animals. This laboratory uses
functional magnetic resonance imaging (fMRI) to investigate schizophrenic symptoms.
Two hallmark symptoms of schizophrenia are auditory hallucinations and thought
disorder. Auditory hallucinations may result at least in part in a dysfunction of auditory
speech regions. Thought disorder may result in a dysfunction of the brain regions
involved in semantic processing. Several ongoing fMRI projects examine auditory verbal
processing from early (tone processing) to later stages (e.g. semantic processing). We
also look for correlates between activation in these brain systems and clinical symptoms.
1. The tonotopy and mismatch early auditory processing projects use simple tone
processing to evaluate the integrity of early auditory representations in schizophrenia. 2.
The rapid acoustic processing task is based on recent behavioral, fMRI, and post-mortem
histological studies showing that language lateralization may develop at least in part from
differences in myelination and processing speed in the right and left hemisphere. This
project evaluates very early speech processing in schizophrenia. 3. The semantic
priming project investigates spreading activation within semantic networks and the
relationship between abnormal activation of semantic representations and thought
disorder. 4. The auditory rehearsal project examines activation during the covert
rehearsal of words. This task is designed to activate speech perception/production
regions and will allow us to examine the relationship between activation of these regions
and auditory hallucinations. 5. Several ongoing studies are being done as part of a
nationwide consortium of researchers (FBIRN) whose aim is to develop the infrastructure
and methods to conduct multi-site collaborative functional imaging studies. These
include two calibration tasks, and auditory oddball task, and a sternberg working memory
task; control subjects and schizophrenia subjects are tested on all fBIRN protocols.
Contact:
Cynthia Wible, PhD
Boston VA Med Center Brockton
Psychiatry 116A
940 Belmont St
Brockton, MA 02301
617/308-3072
617/582-6033
[email protected]
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