EARLY IDENTIFICATION AND TREATMENT OF MENTAL DISORDERS IN CHILDREN 
AND ADOLESCENTS

Release Date:  May 17, 2000

PA NUMBER:  PA-00-094 (This PA has been reissued as PA-06-442)

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.

PURPOSE

The National Institute of Mental Health (NIMH) invites research grant 
applications for research on early identification and treatment of mental 
disorders in children and adolescents.  In particular, this announcement 
intends to encourage research on disorders such as schizophrenia, 
schizoaffective disorder, bipolar disorder, major depression, obsessive-
compulsive disorder, and anorexia nervosa, alone or comorbid with other 
common mental or substance abuse disorders.  These disorders are considered 
to be in special need of investigation because of their chronicity, high 
morbidity, and relative dearth of data in children and adolescents.

Research on autism and other pervasive developmental disorders is 
specifically addressed by a separate program announcement ( Research in 
Autism and Autism Spectrum Disorders , PA-98-108), which is located at 
http://grants.nih.gov/grants/guide/pa-files/PA-98-108.html.

Mental disorders often start early in the life course.  Early detection and 
treatment of the disorders may result in a better prognosis and functional 
outcome in adult life.  Little is known on how to identify promptly and 
accurately children and adolescents suffering from early signs of mental 
illness.  The diagnostic interpretation of behavioral symptoms, such as 
extreme mood lability, social withdrawal, and disturbances in perception and 
cognition, is often difficult and at times controversial.  In parallel, the 
available data on the efficacy and safety of treatment interventions for 
these children are very limited.

This initiative calls for more research on the (1) validation of early 
diagnosis of mental disorders in youths, and especially in young children, 
(2) development of new interventions to treat mental disorders and prevent 
the exacerbation of, and functional impairments associated with, these 
disorders, (3) testing of the efficacy and safety of treatments, both new and 
already in use among young patients with mental illness, (4) study of access 
or barriers to services and effectiveness of services for these patients, (5) 
testing of the long-term effectiveness and safety of treatment interventions 
for young patients with chronic or recurrent disorders, (6) assessment of the 
long-term impact of early intervention, especially on disease progression and 
prognosis, (7) identification of early signs of anorexia nervosa that could 
serve as targets for interventions, and (8) identification and evaluation of 
predictors of treatment response for new and existing interventions for 
children and adolescents with mental illness.  Intervention strategies to be 
studied can include pharmacological, psychosocial, and rehabilitative 
interventions, separately or in combination.

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),  Early Identification and Treatment of Mental Disorders in Children and 
Adolescents , is related to the priority areas of the Mental Health and 
Mental Disorders Objectives.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople/

ELIGIBILITY REQUIREMENTS

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.  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) R01, collaborative 
R01, and R21 grant award mechanisms.  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 PA may not exceed five years (three years for the R21).

For all competing R01 applications requesting up to $250,000 per year in 
direct costs and all R21 applications, specific applications 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 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 http://grants.nih.gov/grants/guide/pa-files/PA-99-134.html.

Information on Collaborative R01 applications may be found at  Collaborative 
R01s for Clinical Studies of Mental Disorders,  PAR-98-017, which is located 
at http://grants.nih.gov/grants/guide/pa-files/PAR-98-017.html 

RESEARCH OBJECTIVES

Background

Mental disorders often become evident in adolescence.  Some disorders, such 
as obsessive-compulsive disorder, bipolar disorder, and major depression, not 
uncommonly emerge even earlier in life.  The diagnosis of schizophrenia is 
seldom made in prepubertal years.  In part, this is due to the current 
uncertainty in interpreting symptoms of abnormal cognitive and behavioral 
functioning in childhood.  A few studies on prodromal signs of psychosis in 
children and adolescents have been initiated.  This research may shed light 
on the therapeutic value of very early treatment interventions.  Bipolar 
disorder can be usually recognized during adolescence, but, in many cases, it 
may be difficult to formulate a definitive diagnosis in prepubertal years.  
Controversy exists among experts on how to interpret extreme volatility of 
mood, temper, and behavior in children, and especially in young children.

Arriving at a valid and prompt diagnosis of mental disorder in children is 
essential.  Early diagnosis can lead to appropriate treatment interventions 
and, possibly, to a better prognosis for the patient.  If the disorder is not 
properly recognized, children may be left untreated or exposed to 
inappropriate treatments that may worsen the underlying disorder.  On the 
other hand, an inaccurate diagnosis can lead to unnecessary exposure to 
medications, such as antipsychotics, mood stabilizers, or antidepressants, 
which have potential negative side effects.  Thus, research aimed at 
increasing the ability to arrive at valid and early diagnoses of disorders 
such as schizophrenia, bipolar disorder, and other chronic and impairing 
mental disorders is urgently needed.

No adequate information exists on the efficacy and safety of antipsychotic 
medications prescribed to youths with schizophrenia and other psychotic 
disorders.  This dearth is particularly evident for the atypical 
antipsychotics.  Likewise, limited data are available on the efficacy and 
safety of commonly used mood stabilizers for the treatment of bipolar 
disorder.  Extrapolation of data from adult studies is in general not 
appropriate, especially with respect to safety data, as children may be more 
prone to certain medication side effects than adults.  Controlled studies are 
needed to address these issues, with special emphasis on the long-term impact 
of these treatments on symptoms, disorder prognosis, cognitive functions, and 
development in general.

In the case of obsessive-compulsive disorders, treatments exist, but for many 
patients their impact is limited, as reflected by an average response rate of 
about 60 percent.  This indicates that at least one-third of patients with 
this chronic condition cannot be successfully treated with the current 
modalities.  Novel and more effective interventions are needed.  For anorexia 
nervosa, there is very little known about how to intervene on early symptoms 
in order to change the course of the illness.

Important ethical issues emerge when considering, planning, and conducting 
early treatment research in the prodromal phase of mental disorders.  A 
distinction must be clearly made between treatment of existing symptoms that 
are accompanied by clinical dysfunction, on one hand, and preventive 
interventions for subjects currently at risk but not clinically impaired, on 
the other.  This program announcement focuses on research on clinically 
impairing psychopathology and not on asymptomatic subjects who are at risk 
for mental illness.  Researchers considering studies on prevention of 
psychotic disorders through study of early symptomatic manifestations are 
referred to PA-99-090,  Prevention and Early Intervention in Psychotic 
Disorders , which is located at 
http://grants.nih.gov/grants/guide/pa-files/PA-99-090.html.

Some illustrative examples of research topics that may be addressed under 
this program announcement are:

o  Improving the validity of the diagnosis of mental disorders in children 
and adolescents.

o  Understanding the diagnostic predictive value of early manifestations of 
mood and behavioral dysfunction as presented by children and adolescents, and 
especially young children.

o  Improving the ability to differentiate among possible alternative 
diagnoses, especially for those clinical situations where alternative 
diagnoses can lead to substantially different treatment approaches (e.g., 
bipolar disorder vs. attention deficit hyperactivity disorder or conduct 
disorder).

o  Determining the potential impact of early treatment on the course of 
illness.

o  Testing the efficacy and safety of antipsychotic medications in youths 
with psychosis.

o  Testing the efficacy and safety of mood stabilizing medications in youths 
with bipolar disorder.

o  Testing the efficacy and safety of psychosocial treatment interventions 
for youths with disorders such as schizophrenia, bipolar disorder, 
depression, and anorexia nervosa.

o  Studying the long-term efficacy and safety of pharmacological and 
psychosocial treatments for youths with schizophrenia, bipolar disorder, 
depression and other mental disorders.

o  Studying the possible impact on child development of exposure to 
medications commonly used in the treatment of mental disorders, particularly 
when treatment is long-term and starts in early childhood.

o  Testing the efficacy and safety of psychosocial and pharmacological 
interventions for youths with mental disorders such as schizophrenia, bipolar 
disorder, depression, and anorexia nervosa, when these disorders are comorbid 
with other common psychopathology, such as attention deficit hyperactivity 
disorder and substance abuse.

o  Examining access or barriers to services or models of service delivery 
that optimize treatment access, adherence, or satisfaction with services.

o  Investigating the impact of school, health services or models of 
coordination of delivery systems on outcomes for youth with chronic and 
impairing mental disorders.

o  Developing and testing treatment approaches for youths with chronic and 
impairing psychopathology that can be adequately described and quantified, 
even if it does not meet full diagnostic criteria for a  disorder  as defined 
in the current nosology.

o  Developing new treatment approaches for youths with severe forms of 
obsessive-compulsive disorder that have proven unresponsive to usual 
treatments.

o  Elucidating and addressing the ethical implications of early treatment vs. 
non-treatment in situations of diagnostic uncertainty.

o  Comparing the effects of alternative, promising treatment strategies.

o  Determining the risk/benefit ratio of treating children and adolescents 
with early manifestations of psychosis, bipolar disorder, and recurrent 
depression and other chronic and impairing mental disorders.

o  Identifying and characterizing individual, family, and/or cultural factors 
that facilitate or impede early identification, detection, and treatment of 
chronic and impairing mental illness in youth.

o  Identifying and characterizing current practice patterns for youths with 
chronic and impairing mental illness, studying variables that affect quality 
of care, and developing and testing interventions designed to improve quality 
of care for youths with these psychiatric disorders.

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: 
http://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: 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.

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.

APPLICATION PROCEDURES

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: 
[email protected].  Applications are also available on the World Wide Web 
at: http://grants.nih.gov/grants/forms.htm.

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 $250,000 per year ($125,000 for R21).  
(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:

PHS 398

o  FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs 
(in $25,000 increments up to a maximum of $250,000 or $125,000 for R21) 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 
application.

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.

o  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.

o  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.

Applications not conforming to these guidelines will be considered 
unresponsive to this PA and will be returned without further 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 
http://grants.nih.gov/grants/guide/notice-files/not98-030.html

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)

REVIEW CONSIDERATIONS

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 convened by NIH in accordance 
with the 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.

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 
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.

AWARD CRITERIA

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

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

Direct inquiries regarding programmatic issues about diagnosis and detection 
of mental disorders to:

Editha D. Nottelmann, Ph.D.
Division of Mental Disorders, Behavioral Research and AIDS
National Institute of Mental Health
6001 Executive Boulevard, Room 6193, MSC 9617
Bethesda, MD 20892-9617
Telephone:  (301) 443-9734
FAX:  (301) 480-4415
Email:  [email protected] 

Direct inquiries regarding programmatic issues about testing effects of 
treatment interventions to:

Benedetto Vitiello, M.D.
Division of Services and Intervention Research
National Institute of Mental Health
6001 Executive Boulevard, Room 7147, MSC 9633
Bethesda, MD 20892-9633
Telephone:  (301) 443-4283
FAX:  (301) 443-4045 
Email:  [email protected] 

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
Email:  [email protected] 

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.

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