DEPRESSION AND MENTAL DISORDERS IN DIABETES, RENAL DISEASE, AND 
OBESITY/EATING DISORDERS

Release Date:  September 28, 2001

RFA:  RFA-DK-02-009

National Institute of Diabetes and Digestive and Kidney Diseases
 (http://www.niddk.nih.gov)
National Institute of Mental Health
 (http://www.nimh.nih.gov)

Letter of Intent Receipt Date:  January 18, 2002
Application Receipt Date:       February 20, 2002

THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  MODULAR 
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS REQUESTING LESS 
THAN $250,000 PER YEAR IN ALL YEARS. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED 
IN SECTION C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

PURPOSE

There is substantial evidence that severe chronic illness may be associated 
with and exacerbated by co-existent mental disorders such as depression, 
anxiety disorders, schizophrenia, and eating disorders.  Nonetheless, few 
studies have addressed the natural history and consequences of co-existent 
mental disorders on chronic diseases of interest to the NIDDK, such as 
diabetes mellitus, chronic renal disease and obesity and eating disorders.  
Similarly, few studies have addressed the natural history and consequences of 
co-existent diabetes, chronic renal disease, and obesity on mental disorders 
such as depression, anxiety disorders, schizophrenia, and eating disorders.  
In addition, the effect of treating and reducing mental disorders on the 
outcomes of chronic medical illnesses, and the effect of good management of 
the medical illness on the outcome of mental disorders have not been 
delineated.   The effects of intervening to prevent or treat chronic medical 
illness on mental disorder outcomes have not been adequately investigated.  
The purpose of this RFA is to increase research activity in the field of 
mental disorders in relationship to diabetes mellitus, chronic renal disease 
and obesity and eating disorders.
 
This RFA is based on recommendations made by a recent NIDDK/NHLBI/OBSSR 
Working Group and Conference on Depression and Mental Disorders in Diabetes, 
Renal disease, and Obesity/Eating disorders.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of “Healthy People 2000,” a PHS-
led national activity for setting priority areas. This Request for 
Applications (RFA), Depression and Mental Disorders in Diabetes, Renal 
Disease, and Obesity/Eating Disorders, is related to one or more of the 
priority areas.  Potential applicants may obtain a copy of “Healthy People 
2000” at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic, 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, however; 
foreign organizations may participate if they are components of domestic, 
U.S. organizations or via contractual or consortium agreements with domestic, 
U.S. organizations.  Racial/ethnic minority individuals, women, and persons 
with disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) research project 
grant (R01) award mechanism and the R21 exploratory/developmental grant award 
mechanism.  Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  The total project 
period for an application submitted in response to this RFA may not exceed 
five years for the R01 and two years for the R21. This RFA is a one-time 
solicitation. Future unsolicited competing continuation applications will 
compete with all investigator-initiated applications and be reviewed 
according to the customary peer review procedures.  The anticipated award 
date is September 2002.

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts that have been adopted by the 
NIH. Complete and detailed instructions and information on Modular Grant 
applications have been incorporated into the PHS 398 (rev. 5/2001).  
Additional information on Modular Grants can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm

FUNDS AVAILABLE

The ICs intend to commit approximately $1,500,000 in FY 2002 to fund 4 to 8 
new and/or competitive continuation grants in response to this RFA.  An 
applicant may request a project period of up to five years for the R01 
mechanism and two years if the R21 mechanism is used. The requested budget 
for an R21 may not exceed $150,000 in direct costs per year. Because the 
nature and scope of the research proposed may vary, it is anticipated that 
the size of each award will vary.  Although the financial plans of the IC(s) 
provide support for this program, awards pursuant to this RFA are contingent 
upon the availability of funds and the receipt of a sufficient number of 
applications of outstanding scientific and technical merit.  At this time, it 
is not known if competing renewal R01 applications will be accepted and/or if 
this RFA will be reissued.  

RESEARCH OBJECTIVES

Background

Relatively little is known about the epidemiology of depression and other 
mental disorders among individuals with diabetes mellitus, chronic renal 
disease and obesity and eating disorders.  Depression is common in patients 
with both end stage renal disease and diabetes, and there is some evidence 
that depression may sometimes antedate the development of diabetes mellitus.  
Although preliminary data suggest an association between obesity and 
depression, causal relationships between these two conditions are unclear.  
The role of genetic factors, which may confer joint susceptibility to chronic 
medical illness and mental disorders is unknown. 

Observed racial/ethnic differences in the prevalence of mental disorders are 
probably not attributable to intrinsic differences between races, but are 
likely attributable to socioeconomic factors, such as those affecting access 
to care.  The multiple demographic, biological, behavioral, psychosocial, and 
environmental risk factors for the development of co-morbid medical and 
mental disorders have not been clarified in well-characterized populations.  
In addition, the diagnosis of mental disorders in children poses specific 
challenges related to the definition and measurement of these disorders and 
to developmental changes.  Data regarding the prevalence and the course of 
mental disorders in children with diabetes mellitus, chronic renal disease 
and obesity/eating disorders are sparse.   

Stress, including symptoms of depression and anxiety disorders, may interfere 
with the hypothalamic/pituitary/adrenal axis to result in disordered 
carbohydrate and lipid metabolism.  Some symptoms of major depressive 
disorder, such as fatique, insomnia, and reduced appetite,  may be similar to 
symptoms of chronic illnesses.  Mental disorders may make the diagnosis and 
treatment of chronic medical disorders more difficult, and may interfere with 
the ability to treat them.  Similarly, chronic medical disorders may make 
diagnosis, prevention, and treatment of mental disorders more difficult, and 
interfere with interventions aimed at mental disorders.  In addition, mental 
disorders may affect the ability of a patient to effectively adhere to the 
medical regimen and maintain healthy behaviors, or may be associated with 
abnormal regulation of neuroendocrine, cardiologic, metabolic and immunologic 
factors.  The influence of effective treatment of chronic medical illnesses 
on the course of mental disorders, and the effect of successful treatment of 
mental disorders on the outcome of chronic medical illnesses are largely 
unknown.  In addition, whether mental disorder renders medical illness more 
difficult to treat, and whether medical illness impacts the course of mental 
disorders is unknown.  Recent data suggest that certain treatments for mental 
disorders such as schizophrenia, in particular, may be associated with 
abnormal glucose metabolism. 

This RFA is intended to expand understanding of the epidemiology of co-morbid 
mental disorders and selected chronic diseases, the risk factors associated 
with development of illness in vulnerable populations, the association of 
genetic factors with the presence or outcomes of co-morbid medical and mental 
illness, the association of mediators with outcomes in patients with mental 
disorders and chronic medical illnesses, and the results of preventive 
interventions and treatment of medical and/or mental disorders in patients 
with coexistent medical illnesses. 
Topics of interest include, but are not limited to:

What is the prevalence of co-morbid mental disorders and diabetes 
mellitus, renal disease, and obesity/eating disorders?  Are there 
identifiable patterns of distribution in the population that might guide 
targeted intervention efforts?

What are the biological, behavioral, psychosocial, cultural, and 
environmental risk and protective factors linking mental and medical 
disorder.  Which of these factors account for the greatest relative variance 
in the prevalence of the disorders.  And, which of these factors are 
modifiable through intervention?

o Does treatment of depression decrease morbidity/mortality in patients 
with diabetes, chronic renal disease or obesity and what methods of treatment 
are most effective? 

Do interventions for diabetes, chronic renal disease, or obesity 
reduce the risk for mental disorders?  Which preventive interventions or 
treatments are most effective?

Does the depression/diabetes relationship differ for type 1 and 
type 2 diabetes?

o What is the role of diabetes complications in the depression/diabetes 
relationship?

o What is the role of obesity in the depression/diabetes relationship?

o Are there subgroups in which depression is related to obesity and what 
are the common physiological or psychological mechanisms, and symptom 
profiles for these groups?

o Does treatment for depression prevent or delay diabetes onset or 
diabetes complications? 

Do preventive or treatment interventions for diabetes, renal 
disease, and obesity reduce the risk for mental disorders?

o What factors permit an individual who experiences one episode of 
depression in the context of diabetes, renal disease or obesity, to recover?

o Based on controlled studies, it is known that diabetes doubles the 
likelihood of co-morbid depression.  What are the mechanisms involved?

o What is the role of depression in the nutritional disorders associated 
with chronic renal failure?  Does treatment of depression improve nutritional 
parameters?

Of particular interest are studies that address these or related topics in 
children, the elderly, women, and underserved, racial/ethnic minority 
populations.

SPECIAL REQUIREMENTS

It is expected that successful applicants will meet once a year in the 
Washington DC area to share knowledge and details of their research progress 
with each other and with NIDDK and NIMH staff.  Specific plans for the 
Principal Investigator to attend such an annual two-day meeting over the life 
of the grant must be outlined in the budget. 

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 was 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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html. 

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 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
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.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the 
policy that was published in the NIH Guide for Grants an Contracts, June 5, 
2000 (Revised August 25, 2000), and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at  
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm
Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application.  In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA to which 
the application is responding.  Although a letter of intent is not required, 
is not binding, and does not enter into the review of a subsequent 
application, the information that it contains allows IC staff to estimate the 
potential review workload and plan the review.  The letter of intent is to be 
sent to the program staff listed under INQUIRIES by the letter of intent 
receipt date listed in the heading of this RFA.

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) 
at http://grants.nih.gov/grants/funding/phs398/phs398.html
are to be used in applying for these grants. This version of the PHS 398 is 
available in an interactive, searchable PDF format.  For further assistance 
contact GrantsInfo, Telephone 301/435-0714, Email: GrantsInfo@nih.gov

All application instructions outlined in the PHS 398 application kit are to 
be followed, with the following requirements for R21 applications:  

1.  R21 applications will use the “MODULAR GRANT” and “JUST-IN-TIME” 
concepts, with direct costs requested in $25,000 modules, up to the total 
direct costs limit of $150,000 per year. 

2. Although preliminary data are not required for an R21 application, they 
may be included.

3.  Sections a-d of the Research Plan of the R21 application may not exceed 
15 pages, including tables and figures.  

4.  R21 appendix materials should be limited, as is consistent with the 
exploratory nature of the R21 mechanism, and should not be used to circumvent 
the page limit for the research plan.   Copies of appendix material will only 
be provided to the primary reviewers of the application and  will not be 
reproduced for wider distribution.  The following materials may be included 
in the appendix:

o Up to five publications, including manuscripts (submitted or accepted 
for publication), abstracts, patents, or other printed materials 
directly relevant to the project.  These may be stapled as sets.
o Surveys, questionnaires, data collection instruments, and clinical 
protocols.  These may be stapled as sets.
o Original glossy photographs or color images of gels, micrographs, etc., 
provided that a photocopy (may be reduced in size) is also included 
within the 15 page limit of items a-d of the research plan

The RFA label available in the PHS 398 (rev. 5/2001) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA 
number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

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 NIH staff.  The research grant application form PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in 
applying for these grants, with modular budget instructions provided in 
Section C of the application instructions. 

Submit a signed, typewritten original of the application, including the 
Checklist, and three 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)

At the time of submission, two additional copies of the application must be 
sent to:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard, Rm. 752
Bethesda, MD  20892-5452
Bethesda, MD  20817 (for express/courier service)

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will 
be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an Introduction addressing the previous critique.

REVIEW CONSIDERATIONS 

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIDDK and NIMH staff.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further consideration.
Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NIMH and the NIDDK in accordance with the review criteria 
stated below.  As part of the initial merit review, a process will be used by 
the initial review group in which applications 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 the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the National Advisory Council or Board for the relevant Institute.

Review Criteria

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 
alternative tactics?

(3) Innovation: Does the project employ novel concepts, approaches or method?  
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 
support?

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 
evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

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.

The initial review group will also examine the provisions for the protection 
of human subjects and the safety of the research environment.

SCHEDULE

Letter of Intent Receipt Date:    January 18, 2002
Application Receipt Date:         February 20, 2002
Peer Review Date:                 June/July 2002
Council Review:                   September 2002
Earliest Anticipated Start Date:  September 2002

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Sanford Garfield, Ph.D. 
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 685
Bethesda, MD  20892-5460
Telephone:  (301) 594-8803
FAX:  (301) 480-3503
E-mail:  sg50o@nih.gov

Peter Muehrer, Ph.D. 
Division of Mental Disorders, Behavioral Research and AIDS
National Institute of Mental Health
6001 Executive Blvd., Room 6189
Bethesda, MD  20892-9615
Telephone:  (301) 443-4708
FAX:  (3010 443-4415
E-mail:  pm29v@nih.gov

Direct inquiries regarding fiscal matters to:

Cheryl Chick
Division of Extramural Activities 
National Institute of Diabetes and Digestive and Kidney Diseases 
6707 Democracy Boulevard, Rm. 606
Bethesda, MD  20892-5456
Telephone:  (301) 594-8825
FAX:  (301) 480-3504
E-mail:  cc149o@nih.gov

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
E-mail:  dt21a@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.847 (NIDDK) and 93.242 (NIMH).  Awards are made under the authority 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 Part 52 and 45 CFR parts 74 and 92.  
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 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, any 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.


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