RESEARCH ON DEPRESSION COMORBID WITH EXTERNALIZING PROBLEMS IN CHILDREN

Release Date:  May 24, 2000

RFA:  MH-01-002

National Institute of Mental Health
National Institute on Drug Abuse

Letter of Intent Receipt Date:  August 18, 2000 
Application Receipt Date:       September 18, 2000

THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  THIS RFA INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING AN APPLICATION IN RESPONSE TO THIS RFA.

PURPOSE

This Request for Applications (RFA) solicits Research Grant Award applications 
from qualified applicants for research on early identification of depression 
(Dysthymic Disorder and/or Major Depressive Disorder) comorbid with disruptive 
behavior problems or disorders (persistent antisocial behavior, attention 
deficit hyperactivity disorder, oppositional-defiant disorder, and conduct 
disorder) in children under 12 years of age in pre-school, school, pediatric 
care, and other settings – and for intervention research designed to treat or 
prevent these comorbid conditions.  Encouraged is research using dimensional (in 
addition to categorical) approaches to identify risk for the development of 
comorbid depressive and disruptive disorders, protective factors, and 
opportunities for intervention.  Also of interest are applications relating 
comorbid depressive and disruptive disorders to risk for later substance abuse 
outcomes.

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 Request for Applications (RFA), 
“Research on Depression Comorbid with Externalizing Disorders in Children,” is 
related to the priority area of mental health and mental disorders.  Potential 
applicants may obtain a copy of "Healthy People 2010" 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 for projects to be 
funded for this program.  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) Small Grant (R03), 
Exploratory/Development Grant for MH Intervention Research (R21), or Research 
Project Grant (R01) award mechanism.  The total project period for an 
application submitted in response to this RFA may not exceed two years for the 
R03 application (funding limited to $50,000 in direct costs per year), three 
years for the R21 application (funding up to $125,000 per year) and five years 
for the R01 application (funding limited to $350,000 per year).  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 earliest 
award date is March 1, 2001.

For all competing R03, R21, and R01 applications, 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: 
https://grants.nih.gov/grants/funding/modular/modular.htm.

Special requirements and instructions for R03 applications may be found at 
https://grants.nih.gov/grants/guide/pa-files/PAR-99-140.html.  Special 
requirements and instructions for R21 applications may be found at: 
https://grants.nih.gov/grants/guide/pa-files/PA-99-134.html

FUNDS AVAILABLE

The NIMH intends to commit approximately $2,000,000 in FY 2001 to fund 
approximately six new and/or competitive continuation grants in response to this 
RFA.  NIDA will also commit $200,000 in FY 2001 to support and co-fund grants 
that address substance use/abuse as well as mental health questions.  An 
applicant may request a project period of up to two years and a budget up to 
$50,000 in direct costs per year for an R03; up to three years and a budget of 
up to $125,000 in direct costs per year for an R21; and up to five years and a 
budget up to $350,000 in direct costs per year for an R01.  Because the nature 
and scope of the research proposed may vary, it is anticipated that the size of 
each award will also vary.  It is expected that direct costs will be awarded in 
modules of $25,000; however, program and grants management adjustments may be 
necessary prior to award.  Although the financial plans of the Institute 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.

RESEARCH OBJECTIVES

Background

In child psychopathology, comorbidity of disorders seems to be the rule rather 
than the exception, and depressive disorders tend to predominate in comorbidity 
profiles.  Depressive disorders co-occur not only at high rates with other 
affective disorders (i.e., anxiety disorders), but also at high rates with 
disruptive disorders, such as Attention Deficit Hyperactivity Disorder (ADHD), 
Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD).  There is 
evidence that childhood-onset depression conveys significant risk for continuing 
major depression and depression-related impairment, as well as for other 
clinical disorders.  However, the relative clinical significance of comorbid 
depressive disorders – and particularly those comorbid with disruptive disorders 
for course and outcome is unclear.  Studies have found that individuals with 
comorbid affective and externalizing disorders face significantly elevated risk 
for substance use disorder outcomes.  Outstanding questions include the 
following: whether comorbid depressive conditions are etiologically distinct 
from non-comorbid depressive conditions, whether different patterns of 
comorbidity represent different subtypes, and whether variation in developmental 
paths depends on age at onset of the comorbid disorders (is the onset of ADHD or 
ODD likely to precede or to co-occur with the onset of depression and onset of 
CD more likely to follow the onset of depression).  Also outstanding are the 
following questions related to substance use outcomes: which children with 
comorbid conditions are at risk, what is the mechanism of risk, and what is the 
developmental course for those children with comorbid conditions who go on to 
develop problems with substance use.  Evaluation of these comorbid conditions 
and their impact on course and outcome clearly presents a major challenge.  
Distinction between symptoms of disorders that portend long-term difficulties, 
for peer relationships and success in school, and substance use, abuse, and 
dependence, from those indicative of serious, but transient problems would be 
particularly useful.

Similarly, comorbidity of depressive and disruptive disorders poses a challenge 
for treatment and preventive interventions.  Issues include questions of which 
psychosocial and/or psychopharmacological treatments, alone or in combination, 
or which services targeting depression and/or disruptive behavior are most 
effective for patients with these comorbid conditions, and for the prevention of 
later sequelae, including substance abuse.

Research Goals and Topics

Studies responsive to this RFA should focus on depression comorbid with 
disruptive disorders in children under 12 years of age; e.g., on sequential 
comorbidity or concurrent comorbidity, including etiology, functional 
impairment, course, treatment, and outcome.  Of particular interest is the 
clinical course of psychopathology;  i.e. the significance of elevated symptom 
levels over time, as well as the way that depressive symptoms may precede or 
follow disruptive behavior problems and/or disorders as a cause, consequence or 
concomitant of disruptive behavior problems and/or disorders.  Approaches that 
examine basic processes on cognition, emotions, attention, and motivation and 
their role in risk taking, aggressive and disruptive behavior, suicidality, and 
later substance use are encouraged.  Also of interest are the early 
identification of risk and protective factors (e.g., mediating and moderating 
influences of life events and social contexts, such as family, school peer 
group) and development of strategies for intervention and prevention, including 
the prevention of recurrence.

The following illustrate suitable approaches:

o  Short-term longitudinal assessment of the course of depressive disorders in 
children who have significant disruptive behavior problems or of course of 
disruptive disorders in children who have significant symptoms of depression

o  Secondary analysis of longitudinal data sets from studies of childhood 
psychopathology that contain information on comorbidity of depressive and 
disruptive symptoms and/or disorders and adverse outcomes, including substance 
use disorders

o  Identification and examination of risk factors and sequencing of risk factors 
for comorbid internalizing and externalizing behavior problems and/or disorders

o  Expansion of ongoing large-scale longitudinal studies on disruptive behavior 
or depressive disorders to include assessments that will allow examination of 
comorbid depressive and disruptive disorders

o  Development and evaluation of early recognition and intervention programs in 
preschool and pediatric primary care settings (e.g., social problem solving 
skills training)

o  Clinical trials testing the effects of treatment interventions for children 
suffering from comorbid depressive and disruptive behavior psychopathology

o  Studies testing the impact of mental health services for children suffering 
from comorbid depressive and disruptive behavior psychopathology on current 
functioning and later adverse outcomes, including substance use

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:
https://grants.nih.gov/grants/guide/notice-files/not94-100.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: https://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators also may obtain copies of the policy from the program staff listed 
under INQUIRIES.  Program staff may also provide additional relevant information 
concerning the policy.

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.

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 in response to 
which the application may be submitted.  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 Institute staff to estimate 
the potential review workload and avoid conflict of interest in the review.

The letter of intent is to be sent to the program staff listed under INQUIRIES 
by August 18, 2000.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms 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.  The application is also available at 
https://grants.nih.gov/grants/funding/phs398/phs398.html

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 below.

BUDGET INSTRUCTIONS

Modular Grant applications will request direct costs in $25,000 modules, up to a 
total direct cost request of $350,000 per year.  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:

PHS 398

o  FACE PAGE:  Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $350,000) 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 (rev 4/98).  It is not required nor will it be accepted at the 
time of application.

o  BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT:  Do not complete the 
categorical budget tables on page 5 of the PHS 398 (rev. 4/98) Form.  It is not 
required and will not be accepted with the application.

o  NARRATIVE BUDGET JUSTIFICATION:  Prepare a Modular Grant Budget Narrative 
page.  (see https://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 role 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 
arrangement 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.

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:
https://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, in 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.

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application and must display the 
RFA number MH-01-002.  A sample modified mailing label is available at: 
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.  Please note this is 
in pdf format.  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, RESEARCH ON DEPRESSION COMORBID 
WITH EXTERNALIZING PROBLEMS IN CHILDEREN, MH-01-002, 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 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:

Henry J. Haigler, Jr., Ph.D.
Division of Extramural Activities
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 6154, MSC 9607
Bethesda, MD 20892-9607 
Bethesda, MD 20852 (for express/courier service)

Applications must be received by September 18, 2000.  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 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 
NIMH 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 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 the applications under review, will be discussed, 
assigned a priority score, and receive a second level review by the National 
Advisory Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
depression comorbid with externalizing behavior problems in children.  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, 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 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 support?

The initial review group will also examine: the appropriateness of proposed 
project budget and duration; the adequacy of plans to include both genders, 
minorities and their subgroups, and children as appropriate for the scientific 
goals of the research and plans for the recruitment and retention of subjects; 
the provisions for the protection of human and animal subjects; and the safety 
of the research environment.

Schedule

Letter of Intent Receipt Date:    August 18, 2000 
Application Receipt Date:         September 18, 2000
Peer Review Date:                 October/November 2000
Council Review:                   May 2001
Earliest Anticipated Start Date:  July 2001

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 other than application/testing of 
existing interventions to:

Editha D. Nottelmann, Ph.D.
Division of Mental Disorders, Behavioral Research & AIDS
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 6200, MSC 9617
Bethesda, MD 20892-9617 (or Rockville, MD 20852 for express/courier)
Telephone: (301) 443-9734
FAX: (301) 480-4415
Email: enottelm@nih.gov

Direct inquiries regarding programmatic issues of application/testing of 
existing interventions to:

Benedetto Vitiello, M.D.
Division of Services and Intervention Research
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 7149, MSC 9633
Bethesda, MD 20892-9633 (or Rockville, MD 20852 for express/courier)
Telephone: (301) 443-4283
FAX: (301) 443-4045
Email: bvitiell@nih.gov

Direct inquiries regarding programmatic issues related to drug abuse outcomes 
to:

Naimah Weinberg, M.D.
Division of Epidemiology, Services & Prevention Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 5153, MSC 9589
Bethesda, MD 20892-9589 (or Rockville, MD 20852 for express/courier)
Telephone:  (301) 402-1908
FAX:  (301) 443-2636
Email: nw46w@nih.gov

Direct inquiries regarding fiscal matters to:

Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605 (or Rockville, MD 20852 for express/courier)
Telephone:  (301) 443-2805
FAX:  (301) 443-6885
Email:  Diana_Trunnell@nih.gov

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD 20892-9541 (or Rockville, MD 20852 for express/courier)
Telephone:  (301) 443-6710
FAX:  (301) 594-6847
Email: gf6s@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.242 (NIMH) or 93.279 (NIDA).  Awards are made under authorization of the 
Public Health Service 5600 Fishers Lane 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 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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