WOMEN’s MENTAL HEALTH AND GENDER DIFFERENCES RESEARCH
Release Date: March 6, 2000
PA NUMBER: PA-00-074 (see replacement PA-03-143)
National Institute of Mental Health
THIS PA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. THIS PA INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED
WHEN PREPARING AN APPLICATION IN RESPONSE TO THIS PA.
The National Institute of Mental Health (NIMH) invites grant applications
from investigators for research on women's mental health and gender-related
differences in mental disorders. This program announcement is a revision of
PA 95-061 Women’s Mental Health Research , issued in 1995. The NIH Office
of Research on Women’s Health, in its 1999 publication Agenda for Research
on Women’s Health for the 21st Century, highlighted multiple factors that
impact on women’s health across the life span. The field of women’s health
was defined in that report as encompassing biomedical, behavioral, and
psychosocial research on girls and women. It extends in scope beyond a
traditional focus on women’s reproductive health to include disorders and
conditions more prevalent in females than in males, or different in clinical
features and risk factors.
Of all demographic variables in epidemiological research, gender is the
single strongest correlate of risk for different types of mental disorders.
Despite the robustness of this correlation, gender itself is a proxy term
for a complex of biological, behavioral, and psychosocial variables and
processes, which remain as yet incompletely understood. Depressive disorders
and most anxiety disorders are, on average, two to three times more common in
females than males. Eating disorders are eight to ten times more common in
females. Males are more likely to be affected by developmental disorders
such as autism and attention deficit disorder and by substance and alcohol
abuse and conduct disorders. For all disorders, including those more common
in males than females and those in which gender prevalence is equal (e.g.
schizophrenia; bipolar disorder), gender-related differences may occur in
etiological risk factors or in clinical aspects. Gender differences in such
features as neuropsychological profiles, risk for onset or recurrence,
symptom severity, or disability have important practical significance for
treatment and services needs.
Mental disorders are major sources of disease-related disability. The Global
Burden of Disease report (Murray and Lopez, 1996) identified major
depression, bipolar disorder, schizophrenia and obsessive-compulsive disorder
as among the ten leading sources of disease-related disability in women
In general, women are the primary consumers of treatments and services for
mental disorders, but there is little consideration of epidemiological and
clinical findings of gender differences applied to public mental health
policy and services delivery systems.
The majority of serious mental disorders have an onset in early adulthood or
adolescence and a recurrent or chronic course. Thus the social impact of
mental disorders falls disproportionately on women during the childbearing
and childrearing years suggesting the need for more intervention research for
women during pregnancy and lactation.
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas. This Program Announcement
(PA), Women’s Mental Health Research, is related to the priority areas of
mental health and mental disorders. Potential applicants may obtain a copy
of "Healthy People 2010" at http://www.health.gov/healthypeople
Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government. Foreign institutions are not eligible
for R03 and P01 grants. Racial/ethnic minority individuals, women, and
persons with disabilities are encouraged to apply as principal investigators.
MECHANISM OF SUPPORT
This PA will use the National Institutes of Health (NIH) the R01, R21, R03
and P01 mechanisms. The Small Grant (R03) provides two years of funding with
a maximum of $50,000 direct costs for each year. The
Exploratory/Developmental Grant (R21) provides three years of funding with an
average of $125,000 direct costs for each year; it is intended for pilot
testing of interventions and other aspects of intervention development. The
total project period for an application submitted in response to this PA may
not exceed five years for an R01 award. Responsibility for the planning,
direction, and execution of the proposed project will be solely that of the
For all R03 and R21 applications, as well as all competing R01 applications
requesting up to $250,000 direct costs per year, specific application
instructions have been modified to reflect MODULAR GRANT and JUST-IN-TIME
streamlining efforts being undertaken at NIH. More detailed information
about modular grant applications, including a sample budget narrative
justification pages and a sample biographical sketch, is available via the
Internet at: http://grants.nih.gov/grants/funding/modular/modular.htm.
Applications that request more than $250,000 in any year must use the
standard PHS 398 (rev. 4/98) application instructions.
Because many grant mechanisms have special eligibility requirements,
application formats, and review criteria, applicants are strongly encouraged
to consult with program staff (listed under INQUIRIES) and to obtain the
appropriate additional announcements for those grant mechanisms.
Special instructions and information for the small grant program is found via
the Internet at:
http://grants.nih.gov/grants/guide/pa-files/PAR-99-140.html. R03s are not
Because the R21 grants have a special application format and review criteria,
applicants are strongly encouraged to consult with program staff (listed
under INQUIRIES) and to obtain the appropriate additional announcements for
those grant mechanisms. Special instructions and information for the
Exploratory/Development Grants for MH Intervention Research, can be found at
The program project (P01) grant mechanism supports broadly based,
multidisciplinary, multi-project, often long-term research programs that have
a specific major objective or basic theme. To qualify for support, a program
project must consist of at least three research subprojects as recommended by
peer review. Applications may request support for up to five years.
Annual awards will be made subject to continued availability of funds
and progress achieved. All applicants for program project grants are strongly
encouraged to discuss their proposals prior to submission with program staff.
This program announcement identifies five areas for research emphasis.
Because of the complexity of factors influencing women’s mental health,
multidisciplinary, multi-method research is encouraged. Despite clear gender
differences in prevalence of different mental disorders, there is relatively
little linkage between epidemiological, etiological and intervention
research. In this announcement, therefore, translational research is
There is as yet an imprecise lexicon to describe differences in health
status, etiology, progress, and treatment of disease between men and women.
This difficulty reflects persistent conceptual lack of clarity related to the
roles of biological, social and cultural factors in differences. In what
follows, the term gender is used to refer to multiple processes and
factors. However, investigators are encouraged to discuss their conceptual
models of gender differences in their applications. The specific research
topics and questions given below are illustrative only and are not intended
to limit research in this area.
Brain and behavior research
There is increased recognition that biologically mediated gender differences
influence behavioral outcomes and may modify vulnerability to different
mental disorders, severity of course, or response to different treatments.
Included here are basic studies in animals and humans as well as human
clinical studies in subjects with mental disorders.
Examples of research areas include studies of:
o Gender differences in brain and behavior including structural and
functional brain imaging of normative and clinical samples
o Gender differences in the molecular and cellular bases of behavior, e.g.
neurotransmitter levels and transporters, receptor subpopulations and enzyme
o Gender differences in genetic factors, including differences in gene
expression or gene-environment interaction in relation to mental disorders
o Gender differences in the developmental-organizing and activating
influences of sex steroids on brain and behavior and interactions with
thyroid- and hypothalamic-pituitary adrenal axes, the immune system and
o Gender differences in the pharmacokinetics, pharmacodynamics and
pharmacogenetics of psychotropic medications in relation to hormonal status
and developmental phase
Bio-behavioral dysregulation and adaptation to stress
Evidence is accruing that response to stress may be mediated both by sex
steroids as well as by experiential differences between men and women.
Animal and human studies indicate that gender differences in hormonal factors
may modulate physiological and behavioral response to stress.
Epidemiological studies show that women are more likely to have experienced
certain kinds of stress (e.g. childhood and adult sexual abuse), which are
risk factors for mental disorders. Research also indicates that women are
twice as likely as men to develop stress-related disorders and depression
following exposure to traumatic events. To understand this complex area,
multiple approaches are required, ranging from basic developmental and
plasticity research to human clinical studies.
Examples of research areas include studies of:
Appetite, aggression, exploration, sleep, energy, mood and their
biological rhythms as they are differentially regulated and dysregulated in
males and females and in relation to mental disorders
Developmental differences in males and females in risk for,
exposure to, and response to, social and physical environmental variables,
including stressors and trauma
o The impact of stress at different developmental stages on gender-
differentiated physiological and behavioral responses and risk for mental
o Biological, psychosocial and psychopathological correlates and
consequences of violence and abuse of women and girls
Epidemiological and clinical studies of disorders
During the past two decades, advances in diagnosis and survey methodologies
have enabled researchers to establish general estimates of the impact and
service needs of adult women with mental disorders. This work remains to be
done for younger females. The need for such research is particularly
pressing, since in many disorders, gender differences emerge first in
adolescence when early intervention strategies may be most effective in
preventing full-blown mental disorders. Later in the lifespan, there is
relatively little information on gender related factors in such important
clinical aspects of disorders as risk for recurrence, chronicity, comorbidity
and disability. Studies encouraged here include those of epidemiology,
diagnosis, lifespan development and course of mental disorders in females.
Studies are also encouraged for gender differences in social, behavioral, and
biological risk factors for mental disorders.
Examples of research areas include studies of:
o Health disparities so as to identify, understand and target the burden of
mental illness and related disability, and to improve treatment and services
utilization among women and girls of different ethnic and socioeconomic,
o Reliability, validity and predictive value of diagnostic classifications
and instruments for female populations
o Taxonomies of functional outcomes and disabilities in women and girls with
mental disorders and instruments to measure functional changes following
o Screening and identification of high-risk women and girls in primary care
settings (e.g., general medical settings and obstetric-gynecology
settings)for mental illness
o Demographic variables and cultural and social factors (e.g. work and
family roles, marriage, gender discrimination; propensity to use substances)
in relation to gender differences in mental disorders
o Childhood risk and protective factors related to the emergence of gender
differences in mental disorders (particular mood, anxiety and eating
Menarche coincides with onset of gender disparities in incidence of
depression and eating disorders. Menstruation is associated with severe mood
variations in a small percentage of women. Since variance in hormonal levels
per se has been found to have little correlation with mood or mood change in
human research, there is need for studies of the interaction of multiple
biological, clinical and environmental factors. Pregnancy and recent
childbearing may be associated with higher rates of depressive disorders.
This association, as well as the fact that psychotropic drugs are commonly
prescribed for women of childbearing age, raises special gender-related
clinical and treatment considerations. Bioethical issues in the conduct of
clinical research take on added importance since psychotropic agents have the
potential to affect the fetus or nursing child.
Examples of research include studies of:
o The role of hormonal, biological and social factors in:
- emergence of gender differences in mental disorders during adolescence
- etiology and course of mental disorders and premenstrual, pregnancy,
postpartum and perimenopausal mood changes
- age-related health and cognitive changes in pre-menopausal, post-menopausal
and elderly women with a history of mental disorders
o The impact of maternal disorders on outcome of offspring, especially in
relation to clinical and treatment history of mothers during pregnancy
o Interventions to prevent or ameliorate the onset or recurrence of mental
disorders during reproductive transitions. For example, studies of the
effectiveness and safety of interventions in women during pregnancy and
o Interventions for women with serious mental disorders including those
requiring chronic treatment, during pregnancy, postpartum or other
reproductive transitions that may heighten risk for recurrence or
exacerbation of disorder
Other interventions and services research
In addition to interventions targeted specifically for women during
reproductive transitions, Federally funded phase III clinical trials and
Phase III submissions to the Food and Drug Administration (FDA) for approval
of new treatments for use in both males and females are required to include
sufficient numbers of females to permit analysis of outcome data for gender
differences. This general focus also underscores the need to examine
interventions for their impact separately in males and females, to identify
multiple factors in relation to outcome and to address issues affecting
recruitment and retention of female subjects in trials. Interventions are
defined here to include preventive, treatment, services-system and
Specific examples of research include studies of:
o Gender differences in long-term and short-term treatment outcomes for
mental disorders, including suicide and suicidal behaviors
o Gender-related differences in compliance and side effects of treatments;
and in treatment preferences, expectancies and services use
o Gender differences in health-related behaviors (e.g. diet, exercise,
nutritional, vitamin or herbal supplement use) and their impact on
intervention response in women and girls
o Drug-drug interactions, (e.g. supplements, replacement hormones and
psychotropic medications) in females across the life span
o Interventions incorporating attention to risk factors for mental disorders
more common or different in females than in males (e.g. history of sexual
abuse and violence; caregiver roles; ruminative thinking)
o Interventions targeting the early manifestations or behavioral precursors
of depression, anxiety and eating disorders, other behavioral disorders and
suicidality in girls and adolescent females
o Interventions aimed at multiple comorbid outcomes in women and girls at
risk for mental disorders or diagnosed with mental disorders (e.g. comorbid
anxiety disorders in depression; substance abuse in women with bipolar
disorder and schizophrenia)
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).
All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28,
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol.
23, No. 11, March 18, 1994 available on the web at the following URL address:
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by
the NIH, unless there are scientific and ethical reasons not to include them.
This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
Applicants are strongly encouraged to contact the program contacts listed
under INQUIRIES with any questions regarding their proposed project and the
goals of this PA.
Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted at the standard application deadlines as indicated
in the application kit. Application kits are available at most institutional
offices of sponsored research and from the Division of Extramural Outreach
and Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 710-0267, Email:
GrantsInfo@nih.gov. Applications are also available on the World Wide Web
SPECIFIC APPLICATION INSTRUCTIONS FOR MODULAR GRANTS
The modular grant concept establishes specific modules in which direct costs
may be requested as well as a maximum level for requested budgets. Only
limited budgetary information is required under this approach. The
just-in-time concept allows applicants to submit certain information only
when there is a possibility for an award. It is anticipated that these
changes will reduce the administrative burden for the applicants, reviewers
and Institute staff. The research grant application form PHS 398 (rev. 4/98)
is to be used in applying for these grants, with the modifications noted
Modular Grant applications will request direct costs in $25,000 modules, up
to a total direct cost request of $250,000 per year. (Applications that
request more than $250,000 direct costs in any year must follow the
traditional PHS 398 application instructions.) The total direct costs must
be requested in accordance with the program guidelines and the modifications
made to the standard PHS 398 application instructions described below:
o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs
(in $25,000 increments up to a maximum of $250,000) and Total Costs [Modular
Total Direct plus Facilities and Administrative (F&A) costs] for the initial
budget period. Items 8a and 8b should be completed indicating the Direct and
Total Costs for the entire proposed period of support.
o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page
4 of the PHS 398. It is not required and will not be accepted with the
o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the
categorical budget table on Form Page 5 of the PHS 398. It is not required
and will not be accepted with the application.
o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative
page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for
sample pages.) At the top of the page, enter the total direct costs
requested for each year. This is not a Form page.
o Under Personnel, list key project personnel, including their names,
percent of effort, and roles on the project. No individual salary
information should be provided. However, the applicant should use the NIH
appropriation language salary cap and the NIH policy for graduate student
compensation in developing the budget request.
For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the
nearest $1,000. List the individuals/organizations with whom consortium or
contractual arrangements have been made, the percent effort of key personnel,
and the role on the project. Indicate whether the collaborating institution
is foreign or domestic. The total cost for a consortium/contractual
arrangement is included in the overall requested modular direct cost amount.
Include the Letter of Intent to establish a consortium.
Provide an additional narrative budget justification for any variation in the
number of modules requested.
o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by
reviewers in the assessment of each individual's qualifications for a
specific role in the proposed project, as well as to evaluate the overall
qualifications of the research team. A biographical sketch is required for
all key personnel, following the instructions below. No more than three
pages may be used for each person. A sample biographical sketch may be
viewed at: http://grants.nih.gov/grants/funding/modular/modular.htm
- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;
o CHECKLIST - This page should be completed and submitted with the
application. If the F&A rate agreement has been established, indicate the
type of agreement and the date. All appropriate exclusions must be applied
in the calculation of the F&A costs for the initial budget period and all
future budget years.
o The applicant should provide the name and phone number of the individual
to contact concerning fiscal and administrative issues if additional
information is necessary following the initial review.
Applicants planning to submit an investigator-initiated new (type 1),
competing continuation (type 2), competing supplement, or any amended/revised
version of the preceding grant application types requesting $500,000 or more
in direct costs for any year are advised that he or she must contact the
Institute program staff before submitting the application, i.e., as plans for
the study are being developed. Furthermore, the application must obtain
agreement from the Institute staff that the Institute will accept the
application for consideration for award. Finally, the applicant must
identify, in a cover letter sent with the application, the staff member and
Institute who agreed to accept assignment of the application.
This policy requires an applicant to obtain agreement for acceptance of both
any such application and any such subsequent amendment. Refer to the NIH
Guide for Grants and Contracts, March 20, 1998 at
Any application subject to this policy that does not contain the required
information in a cover letter sent with the application will be returned to
the applicant without review.
The title and number of the program announcement must be typed on line 2 of
the face page of the application form and the YES box must be marked.
Submit a signed, typewritten original of the application, including the
Checklist, and five signed photocopies in one package to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
Applications will be assigned on the basis of established PHS referral
guidelines. Applications will be evaluated for scientific and technical
merit by an appropriate scientific review group in accordance with standard
NIH peer review procedures. As part of the initial merit review, all
applications will receive a written critique and undergo a process in which
only those applications deemed to have the highest scientific merit,
generally the top half of applications under review, will be discussed,
assigned a priority score, and receive a second level review by the
appropriate national advisory council or board.
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals. Each
of these criteria will be addressed and considered in assigning the overall
score, weighting them as appropriate for each application. Note that the
application does not need to be strong in all categories to be judged likely
to have major scientific impact and thus deserve a high priority score. For
example, an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.
(1) Significance: Does this study address an important problem? If the aims
of the application are achieved, how will scientific knowledge be advanced?
What will be the effect of these studies on the concepts or methods that
drive this field?
(2) Approach: Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
(3) Innovation: Does the project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does the project challenge
existing paradigms or develop new methodologies or technologies?
(4) Investigator: Is the investigator appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the principal investigator and other researchers (if any)?
(5) Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will also be
o The reasonableness of the proposed budget and duration in relation to the
o The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project
proposed in the application.
Applications will compete for available funds with all other recommended
applications assigned to the Institute. The following will be considered in
making funding decisions: Quality of the proposed project as determined by
peer review, availability of funds, and program priority.
Inquiries are encouraged. The opportunity to clarify any issues or questions
from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Mary C. Blehar, Ph.D.
Chief, Women’s Mental Health Program
National Institute of Mental Health
6001 Executive Boulevard, Room 8125, MSC 9659
Bethesda, MD 20892-9650
Telephone: (301) 443-2847
FAX: (301) 443-8552
Direct inquiries regarding fiscal matters to:
Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-2805
FAX: (301) 443-6885
The National Institute on Drug Abuse is not participating in this program
announcement, but continues to fund a broad range of Institute-wide human and
animal research focusing on women and gender differences, including studies
on the co-occurrence of drug abuse/addiction and mental disorders. For more
information call or write:
Cora Lee Wetherington, Ph.D.
Women and Gender Research Coordinator,
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda MD 20893-9555
Telephone: (301) 443-1263
FAX: (301) 594-6043
The National Cancer Institute is not participating in this program
announcement but continues to fund research in the area of women’s health
related to cancer survivors and their family members. For more information,
call or write:
Julia H. Rowland, Ph.D.
Director, Office of Cancer Survivorship
National Cancer Institute
6130 Executive Boulevard, Suite 539
Bethesda, MD 20892
Telephone: (301) 402-2746
FAX: (301) 496-8675
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93.242. Awards are made under authorization of the Public Health Service
Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42
USC 241 and 285) and administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review.
The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products. In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, and portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices