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Women’s Mental Health Studies

Women’s Mental Health Studies

Clinical Neuroscience of Sex Differences In The Brain:
Research on Women’s Mental Health

Program Description

The work of this Program of Research has been ongoing over the last 15 years.
It is a unique team of investigators in that we come from different disciplines
to bring our expertise to bear on similar questions about the role of one’s
sex in understanding severe neuropsychiatric disorders. This is important
for the mission of MMHC regarding the treatment of the severely, chronically
mentally ill, for a number of reasons, including: 1) there is a higher prevalence
of men in public sector care; 2) men and women have different cognitive
dysfunctions and strengths; and 3) ill men and women respond differently
to psychopharmacologic, familial, and rehabilitative treatments. Thus, we
need to understand why there are these sex differences in the incidence,
expression and course of these illnesses, in order to improve treatment,
and perhaps, prevention.

Current Research

Studies are elucidating normal sex differences in the brain, in order to
understand how the brain goes awry differentially in men and women with
psychoses. There is also a focus on prenatal and perinatal risk factors
for understanding psychoses and the role of sex. Although schizophrenia
has been the primary focus, affective disorders and neurodevelopmental disorders,
such as dyslexia and attentional disorders, are also of primary interest
as comparison disorders. Studies include sex differences in cognitive functions,
structural brain abnormalities (using MRI), functional brain abnormalities
(using fMRI, psychophysiological response, EEG, and neuroendocrine challenges),
pre-and perinatal risk factors, and the expression and genetics of the disorders.
Recent work has included studies of the impact of gonadal steroid hormones
on brain structure and function, including collaborations with basic neuroscientists
studying gonadal hormones and the brain. We are also investigating the role
of gondadal hormones in understanding treatment response.

History of Program

Dr. Goldstein has assembled a team over the last several years that includes
the fields of psychiatry, epidemiology, neuroendocrinology, neuropsychology
and cognitive neuroscience, radiology, and the basic neuroscience of gonadal
hormones and the brain and molecular genetics, in order to explain sex
differences in major psychiatric disorders. In addition, a number of our
studies are population-based, family studies, which allow for greater
generalization of our findings to the population at large. Our birth cohort
studies are known to the community as the New England Family Studies.
We have formed a novel research program in that its goal is to conduct
and integrate findings from studies using the combined expertise of investigators
from the lab bench to clinical practice. We are fully integrated with
our MMHC Brain Imaging Program in Clinical Neuroscience of Psychotic Disorders
at MGH, which Drs. Seidman and Goldstein co-direct. We have established
good working relationships with MMHC Continuing Care Service, at which
we have conducted studies and provided educational presentations. Finally,
we have integrated investigators from different departments of psychiatry,
and departments of neurology, radiology, and medicine at HMS.

The work of this team began in epidemiology and genetics, in that we
characterized on a population-basis, how men and women differed in incidence,
expression, course, developmental history, and genetic transmission of
psychoses. Findings from this work led the group, over the last 10 years,
to a focus on understanding sex differences in the structure and function
of the brain. We have a number of trainees that have worked with this
team over the last 15 years. They include fellows from the NIMH Psychiatric
Epidemiology and Biostatistics training program, NIMH Psychiatric Genetics
training program, psychiatry fellows (nationally and internationally represented),
psychology and cognitive and behavioral neuroscience trainees, junior
faculty, and undergraduates from the university.

This team has an international reputation. We have received a number
of investigator-initiated research grants from NIMH and national foundations,
current funding totaling approximately several million dollars in research
funding.

Future Goals

Our future plans are to continue to elucidate the nature of and developmental
factors that contribute to explaining sex differences in structural and
functional brain abnormalities in chronic mental disorders. Further, we
have plans to use neuroendocrine challenges and psychopharmacologic challenges
to investigate the role of gonadal hormones and neuroendocrine dysfunction
on treatment response. In addition, we have many training opportunities
and our faculty teach in numerous capacities at HMS and Harvard University.
We will continue to contribute to the mission of MMHC, in that our work
contributes to understanding some of the heterogeneity of chronic mental
illness by elucidating the impact of one’s sex on the etiology and
treatment of the illnesses. Further, we will continue to contribute to the
mission of HMS, in that we have a long history of integrating faculty and
trainees from the basic sciences to clinical practice who come from different
departments at HMS and colleagues from other institutions.

Senior Faculty

Jill M. Goldstein, Ph.D. (Director)
Larry J. Seidman, Ph.D.
Stephen L. Buka, Sc.D.
Stephen V. Faraone, Ph.D.
Ming T. Tsuang, M.D., Ph.D.

Senior Staff

Anne Peters (Project Manager)
Jo-Ann Donatelli, M.S. (Clinical Coordinator)
Monica Landi, M.S.W. (Senior Community Liaison)

Contact Information:

Jill M. Goldstein, Ph.D.
Phone: (617) 626-9395
E-mail: [email protected]

Recent Publications (Last 5 years):

  1. Goldstein, JM, Seidman, LJ, Goodman, JM, Koren, D, Lee, H, Weintraub,
    S, Tsuang, MT. Are there sex differences in neuropsychological functions
    among patients with schizophrenia? Amer J Psychiatry 1998, 155 (10):
    1358-1364.
  2. Goldstein, JM, Goodman, JM, Seidman, LJ, Kennedy, D, Makris, N, Lee,
    H, Tourville, J, Caviness, VS, Faraone, SV, Tsuang, MT. Cortical abnormalities
    in schizophrenia identified by structural magnetic resonance imaging.
    Arch of Gen Psychiatry. 1999, 56: 537-547.
  3. Goldstein, JM, Seidman, LJ, Horton, NJ, Makris, M, Kennedy, DN, Caviness,
    VS, Faraone, SV, Tsuang, MT. Normal sexual dimorphism of the adult human
    brain assessed by in-vivo magnetic resonance imaging, Cerebral Cortex,
    2001, 11:490-497.
  4. Goldstein, JM, Seidman, LJ, O’Brien, L, Horton, N, Kennedy,
    DN, Makris, N, Caviness, VS, Faraone, SV, Tsuang, MT. Impact of normal
    sexual dimorphisms on sex differences in structural brain abnormalities
    in schizophrenia assessed by magnetic resonance imaging. Archives of
    General Psychiatry, 2002; 59:154-164.
  5. Goldstein, JM, Cohen, LS, Horton, NJ, Lee, H, Andersen, S, Tohen,
    M, Crawford, AK, Tollefson, G. Sex differences in clinical response
    to olanzapine compared with haloperidol. Psychiatry Res, 2002; 110:27-37.
  6. Canuso, CM, Goldstein, JM, Wojcik, J, Dawson, R, Brandman, D, Klibanski,
    A, Schildkraut, JJ, Green, AI. Antipsychotic medication, prolactin elevation,
    and ovarian function in women with schizophrenia. Psychiatry Res, 2002;
    111: 11-20.
  7. Goldstein, JM, Seidman, LJ, Buka, SL, Horton, NJ, Donatelli, JL, Zornberg,GL,
    Rieder, RO, Tsuang, MT. Impact of genetic vulnerability and hypoxia
    on overall intelligence by age 7 in offspring at high risk for schizophrenia
    compared with affective psychoses. Schizophr Bull, 2000, 26 (2): 323-334.