Expired RFA-MH-15-500: Dimensional Approaches to Research Classification in Psychiatric Disorders (R01)

Part 1. Overview Information

Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Mental Health (NIMH)
Funding Opportunity Title	Dimensional Approaches to Research Classification in Psychiatric Disorders (R01)
Activity Code	R01 Research Project Grant
Announcement Type	Reissue of RFA-MH-14-050
Related Notices	June 5, 2015 - This RFA has been reissued as RFA-MH-16-510. June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
Funding Opportunity Announcement (FOA) Number	RFA-MH-15-500
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.242
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) seeks research grant applications designed to develop innovative ways of understanding mental disorders in clinical studies on the basis of experimental research criteria rather than traditional diagnostic categories. This FOA stems from the NIMH Research Domain Criteria (RDoC) project that is intended to further a long-range goal of contributing to diagnostic systems as informed by research on genetics, neuroscience, and behavior. The purpose of this FOA is to encourage applications to study mechanisms that may cut across multiple traditional diagnostic categories. Applications submitted in response to this FOA should be based upon RDoC criteria (see http://www.nimh.nih.gov/research-funding/rdoc.shtml for the RDoC criteria developed to date). Five organizing domains have been identified in the draft specification. These include Negative Valence Systems (i.e., aversive motivational dimensions), Positive Valence Systems, Cognitive Systems, Social Process Systems, and Arousal/Regulatory Systems. Consensus workshops and guidance documents on Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Working Memory (subsidiary of Cognitive Systems), and Social Processes, have been completed, and applications must focus on at least one of the constructs that have been defined in these RDoC workshops, as indicated in the workshop proceedings. Interested applicants are encouraged to consult the NIMH RDoC web site (http://www.nimh.nih.gov/research-funding/rdoc.shtml) for current information regarding these constructs.

Key Dates

Posted Date	April 9, 2014
Open Date (Earliest Submission Date)	September 3, 2014
Letter of Intent Due Date(s)	September 3, 2014
Application Due Date(s)	October 3, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	February, 2015
Advisory Council Review	May, 2015
Earliest Start Date	June, 2015
Expiration Date	October 4, 2014
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose and Objectives

The NIMH Strategic Plan calls for the clarification of the underlying causes of mental disorders across the life span, with efforts towards integrating genetic, neurobiological, imaging, behavioral, and clinical data. This FOA addresses Strategy 1.4 of the NIMH Strategic Plan: Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures. NIMH has begun the implementation of Strategy 1.4 via the Research Domain Criteria (RDoC) project. This project, developed by an internal NIMH working group in conjunction with a small group of external consultants, has created a framework and process with which to implement the research classification system called for by Strategy 1.4. The essence of the project is to identify organizing dimensions that cut across multiple disorders as traditionally defined, and to promote research according to these dimensions rather than to traditional diagnostic categories. Applications that focus primarily on validating a DSM diagnostic category will NOT be considered responsive to this funding opportunity. Rather, this FOA encourages projects that are consistent with the organizing dimensions identified by the RDoC project. The RDoC project aims to support development of an integrative scientific literature that can inform future diagnostic systems which will be based on genetics, neuroscience, and psychology. Five organizing domains have been identified in the draft specification. These include Negative Valence Systems (i.e., aversive motivational dimensions), Positive Valence Systems, Cognitive Systems, Social Process Systems, and Arousal/Regulatory Systems. Consensus workshops on these five domains have been completed, and applications must focus on at least one of the constructs that have been identified in the completed RDoC workshops, as indicated in the workshop proceedings. Interested applicants are encouraged to consult the NIMH RDoC web site (http://www.nimh.nih.gov/research-priorities/rdoc/index.shtml) for current information regarding these domains.

This FOA invites submission of research project grant applications that focus on explicating and validating the domains and their subsidiary constructs that have resulted from RDoC consensus workshops. Priority will be given to applications that evaluate relevant constructs via convergent measurement across multiple units of analysis, and applications that would elaborate aspects of the constructs that are underdeveloped. See the Specific Areas of Research Interest section, below, for illustrations.

Background and Rationale

Currently, the diagnosis of mental disorders is based on clinical observations and reports by patients, caregivers, parents, and teachers. This approach, formalized in the Diagnostic and Statistical Manual-III (DSM-III) in 1980 and refined in subsequent DSM versions, has served to improve diagnostic reliability in clinical practice and research. The diagnostic categories represented in the DSM-5 and the International Classification of Diseases-10 (ICD-10), containing virtually identical disorder codes, remain the consensus standard for diagnosis of mental disorders, and are employed for insurance billing, U.S Food and Drug Administration requirements, and other institutional uses. By default, DSM diagnoses have also become standard for characterizing research participants in grant applications and publications.

Its dominance notwithstanding, the DSM diagnostic scheme has not assimilated recent breakthroughs in genetics and neuroscience. Most genetic and neural circuit anomalies appear to link either with multiple DSM diagnostic categories or with narrow subgroups within diagnoses. A questionable assumption that the clusters of self-reported symptoms codified in the DSM define unique and homogeneous disorders could be constraining advances in the biology of mental illness. Consequently inadequate understanding of pathophysiology would in turn hamper the development of better treatments. Notwithstanding these difficulties, there is general consensus at this time that the biology of mental illness is insufficiently developed to support a classification scheme based on the integration of genetics, neuroscience, and psychopathology. The purpose of the RDoC project is to promote such integrative science so that advances in genomics, pathophysiology, and psychology can substantially inform diagnosis.

The purpose of the initial phase of the RDoC project is to promote research employing clinical subjects from multiple diagnostic groups appropriate to the research question, in order to establish construct validity for some proposed organizing dimensions of psychopathology. This is to be done through research on brain-behavior relationships that integrates findings from multiple scientific disciplines. It is hoped that in later stages of development, measures of the integrated constructs can be developed for practical clinical use.

Specific Areas of Research Interest

Potential applicants should read the material at the RDoC website (http://www.nimh.nih.gov/research-priorities/rdoc/index.shtml). This site contains a detailed description of the background, rationale, draft matrix of domains and units of analysis, examples of potential research applications, and results of workshops convened to generate consensus specifications. In accord with the focus on integrative science, each RDoC construct will map onto seven units of analysis: behavior, cells, circuits, genes, molecules, physiology, and self-reports. Note that independent variables may be selected from any of the units of analysis and would typically include subjects from multiple diagnostic groups. Research plans should incorporate dependent variables from at least two units of analysis to converge upon the construct to be studied.

The RDoC project involves a series of consensus workshops, one for each of the organizing domains listed above. The purpose of each workshop is to identify promising constructs within the domain, define each construct (and its overlaps and differences from other constructs), and specify elements at each of the units of analysis that converge on the construct. The draft matrix entries represent elements (genes, molecules, circuit measures, behavioral tasks, questionnaires, etc.) that have been vetted by the workshop process and appear especially promising for inclusion in research plans. Applicants may opt for other relevant measures where a strong justification can be made.

This FOA invites applications to study constructs only that have been addressed by RDoC workshops, and thereby have a definition and list of pertinent elements at each unit of analysis. The FOA also invites evaluation of the continuity of adult RDoC constructs in child and adolescent populations, and the adaptation or development of relevant measures for children. To date, workshops have been completed for Negative Valence Systems, Working Memory, Positive Valence systems, Cognitive Systems, Social Processes, and Arousal/Regulatory systems. The relevant materials can be found at the RDoC website under the heading Workshop Proceedings." Applications may study constructs that are essentially related to the constructs and circuits delineated in the RDoC matrix. For example, emotion regulation is a construct that refers to dynamic regulation of threat-related amygdala activity by the ventromedial prefrontal cortex, and so could be reasonably related to the RDoC threat construct.

Examples of research projects that might be submitted under this FOA include, but are not limited to:

Evaluation of the efficacy of one or more treatments for anxiety symptoms in individuals along a distribution of hyper-reactive amygdalar responses to threat stimuli
Evaluation of the association of DISC1 and DTNBP1 abnormalities with working memory performance along a dimension of anxious or anhedonic mood symptoms
Comparison of anterior insula and superior temporal cortex activity along a dimension of emotional engagement in a sample with trauma history
Evaluation of the relationship of subgenual cingulate activity and serotonergic function along a dimension of emotional dysregulation
Evaluation of the relationship between measures of exaggerated fear response, reports of overall distress and anxiety, and chronicity of internalizing disorders
Evaluation of developmental delay in prefrontal cortical thickness along a dimension of performance on a series of working memory tasks
Longitudinal studies of the extent to which a dimension of relative hypo-reactivity to hyper-reactivity in responding to emotional cues is predictive of the subsequent onset or exacerbation of mood/anxiety symptoms
Evaluation of the relationships between various types of dysregulation in HPA axis activity and the formation of emotional memories for pleasant and unpleasant material

Priority will be given to applications that have a well-justified plan to include patients from multiple diagnostic groups (including Not Otherwise Specified and forme fruste diagnoses) as appropriate for explicating the dimensions and constructs of interest in the study design. Studies that include patients from a single diagnostic group may also be considered if there is a particularly strong justification for examining constructs of interest within one diagnostic category. A defensible approach might be to study all patients presenting themselves at a specialty clinic, e.g., mood disorders clinic, anxiety clinic, or psychotic disorders clinic, regardless of whether they meet criteria for a particular DSM diagnosis.

The intent of this funding opportunity is to stimulate human-only work that is appropriate to the RDoC domains and to constructs that have been identified to date through the RDoC workshop process. An application concerning a dimensional construct that has NOT been defined in one of the RDoC workshops would NOT be considered responsive to this FOA, but may be submitted independently as a standard investigator-initiated application to PA-13-302. Similarly, applications that propose both animal and human studies relevant to RDoC dimensions would NOT be considered responsive to this FOA but may be submitted independently as standard investigator-initiated applications. Although it would be permissible to include multiple RDoC constructs in one research plan, constructs that are the focus of study for this FOA must have been identified by the RDoC workshops completed to date. Applications that propose to study a mix of RDoC-vetted constructs and others that have not been articulated in an RDoC workshop (even if the non-vetted constructs are listed in the draft RDoC matrix but have not been addressed by a workshop) will NOT be considered responsive to this FOA, but may be submitted independently as standard investigator-initiated applications. Investigators should refer to the proceedings of the RDoC workshops, as posted on the NIMH website, to ascertain what RDoC constructs have been defined in each workshop.

Consistent with its continuing interest in the mental health of diverse populations, the NIMH encourages submission of applications that conform to the RDoC requirements of this FOA and that are designed to test well justified hypotheses about differences in the mechanisms of psychopathology in diverse groups.

Section II. Award Information

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New Resubmissions from RFA-MH-14-050, RFA-MH-13-080 The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. The NIMH intends to commit $3,000,000 in FY 2015 to fund 5 or 6 awards.
Award Budget	Application budgets are limited to $400,000 in direct costs.
Award Project Period	The scope of the proposed project should determine the project period. The maximum period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education
Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Hispanic-serving Institutions
Historically Black Colleges and Universities (HBCUs)
Tribally Controlled Colleges and Universities (TCCUs)
Alaska Native and Native Hawaiian Serving Institutions
Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

Small Businesses
For-Profit Organizations (Other than Small Businesses)

Governments

State Governments
County Governments
City or Township Governments
Special District Governments
Indian/Native American Tribal Governments (Federally Recognized)
Indian/Native American Tribal Governments (Other than Federally Recognized)
Eligible Agencies of the Federal Government
U.S. Territory or Possession

Other

Independent School Districts
Public Housing Authorities/Indian Housing Authorities
Native American Tribal Organizations (other than Federally recognized tribal governments)
Faith-based or Community-based Organizations
Regional Organizations
Non-domestic (non-U.S.) Entities (Foreign Institutions)

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed activity
Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
Names of other key personnel
Participating institution(s)
Number and title of this funding opportunity

The letter of intent should be sent to:

Michael Kozak, Ph.D.
Division of Translational Research and Treatment Development
National Institute of Mental Health
6001 Executive Boulevard, Room 7118, MSC 9625
Bethesda, MD 20892-9625
Rockville, MD 20852 (for express/courier service)
Telephone: 301-443-6471
Email: [email protected]

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover