Full Text PA-95-055


NIH GUIDE, Volume 24, Number 15, April 28, 1995

PA NUMBER:  PA-95-055

P.T. 34

  Mental Disorders 
  Drugs/Drug Abuse 
  Disease Prevention+ 

National Institute on Drug Abuse
National Institute of Mental Health


The purpose of this program announcement is to encourage research on
comorbid mental and drug abuse disorders.  One aim of this research
program is to explore and identify etiological and neurobiological
factors that are associated with the co-occurrence of drug
abuse/addiction and mental disorders.  A second aim is to develop new
treatment and prevention interventions for the population afflicted
with these disorders.  A third aim is to develop effective strategies
and procedures for managing the impact of HIV/AIDS on individuals
with comorbid mental and addictive disorders and the impact of
comorbid mental and addictive disorders on persons with HIV/AIDS.  A
fourth aim is to assess existing drug abuse and mental health
treatment interventions and services for persons with mental and
addictive disorders.


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 Program
Announcement, Research on Comorbid Mental and Drug Abuse Disorders,
is primarily related to the priority area of alcohol and other drugs.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).


Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State or 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.
Foreign institutions are not eligible for the First Independent
Research Support and Transition (FIRST) (R29) award.


The mechanisms available for support of this program announcement are
the regular research project grant (R01), the small grant (R03), the
FIRST award (R29), and the clinical cooperative grant (R10).  Because
the nature and scope of the research proposed in response to this
program announcement may vary, it is anticipated that the size of an
award will vary also.



Research has suggested that comorbidity of drug addiction with mental
disorders may have prognostic value and important implications for
the prevention and treatment of drug dependence.  Drugs of abuse and
addiction may precipitate or exacerbate mental disorders; self-
medication for mental disorders may result in drug abuse or
addiction.  The forms of comorbidity may be influenced by the class
of drug abused, the duration of drug use, individual sensitivity to
drug effects and whether the drug effects are acute, or due to
withdrawal or residual conditions.  Knowledge of comorbid disorders
is important because it can enable prevention and treatment services
to be appropriately configured and designed for clinical populations.

The etiology of drug abuse and addiction has been shown to be complex
and multifactorial and influenced by environmental and constitutional
factors.  Increased knowledge of factors influencing drug
abuse/addiction and comorbid mental conditions will be helpful for
patient-treatment matching and maximizing the effectiveness of
available treatment interventions and services.

The importance of a greater focus upon comorbid mental and addictive
disorders is underscored by research studies that suggest there is a
greatly increased risk for substance use disorder for individuals
with various mental disorders compared to those without.  Programs
that focus on drug abuse and dependence and programs that focus on
mental disorders tend not to be integrated with one another and, in
general, tend not to make HIV-related issues a primary focus.
Psychiatric symptoms and drug use are associated with increased HIV
risk behaviors.  This is true in both treatment populations and out-
of-treatment populations.

Clinical studies suggest that people who have a history of comorbid
mental and addictive disorders, when treated for drug addiction, tend
to relapse at a greater rate than those without a history of mental
disorder.  Interventions for the mental disorder appear to reduce the
relapse rate of these individuals.  These findings suggest that
treatment of a comorbid mental condition may prove to be crucial to
effective drug abuse treatment in populations with concurrent mental
and addictive disorders.

It is worth noting that AIDS is a major co-occurring condition among
drug users in the USA.  Injection drug users are the second largest
group of persons with AIDS in this country.  Male injection drug
users who also have sex with men are an important subgroup of
injectors with AIDS, accounting for approximately 20 percent of these
cases.  Also, the majority of cases of AIDS attributed to
heterosexual transmission, were sexual partners of drug users.
Moreover, more than 50 percent of children with AIDS were the
offspring of mothers who either abused drugs or were sexual partners
of persons who did.  Clearly, drug abuse treatment programs and
HIV/AIDS treatment facilities need to treat both drug dependence and
AIDS-related complications, including resulting mental health
conditions such as depressive and anxiety disorders.

Research is encouraged on HIV/AIDS disease issues, including
transmission, disease progression, risk-behavior change and
treatment, in drug abusing populations with comorbid mental
disorders.  A number of studies show that psychiatric comorbidity,
including both diagnosable conditions and subsyndromal levels of
psychiatric symptomatology, is associated with difficulties in
retention in drug abuse treatment and that non-entry to or drop- out
from treatment is associated with higher levels of risk behavior and
higher HIV seroconversion rates.  Other studies suggest lower levels
of adherence to medical regimens and risk reduction recommendations
among drug abusers with comorbid mental disorders.  Moreover, studies
suggest increased rates of depression in HIV seropositive drug
abusing populations that appear to be directly associated with stage
of HIV disease.  In this context, the interaction of HIV issues with
comorbid mental conditions in drug abusing populations requires
further exploration in terms of (1) describing the changes in risk
for morbidity and mortality related to these comorbid mental
conditions and (2) elucidating the mechanisms underlying the effects
of these comorbidities on risk, with the objective of designing
effective prevention and treatment strategies.

Description of Program

Studies under this program announcement may focus on the etiology,
prevention, treatment, and neurobiology of comorbid mental and
addictive disorders.  Neurobiological studies may involve
neuroimaging (e.g., MRI, CT, PET, SPECT, and EEG).  Treatment
research studies may focus on the development, piloting and efficacy
testing of therapeutic interventions.  Prevention studies may focus
upon testing theory-based preventive interventions focused on
reducing the risk of onset and progression of comorbid conditions
prior to clinical diagnosis.  Services research studies are also
appropriate under this program announcement, and may involve analyses
of existing treatment data bases, collection of new data, including
effectiveness studies of strategies for improving services to
comorbid populations.

Studies may be based in a variety of public and private settings
(e.g., hospitals, residential programs, outpatient programs,
community based programs, primary care settings, correctional
settings) and may involve a variety of treatment or non-treatment
populations. The use of multiple outcome domains (e.g., work
performance) as criterion variables is encouraged.  Subpopulations of
children, adolescents, women, minorities, persons in correctional and
parole settings, homeless persons with serious mental illnesses and
drug abuse/addictive disorders, and the elderly experiencing comorbid
mental and addictive disorders are of particular interest.

Examples of Research Topics

Research topics might include, but are not limited to, the following:

Studies involving neuroimaging of individuals with comorbid mental
and addictive disorders to expose evolving neural substrates of

Studies of drug induced neuropsychological deficits in comorbid
mental and addictive disordered populations.  Assessment of these
deficits and their relationship to therapeutic efficacy may be also

Studies of etiological and neurobiological factors that underlie the
co-occurrence of drug abuse/addiction and mental disorders.

Cohort studies of high risk groups ( e.g., children in high drug
abuse areas, children of drug abusers, children of individuals with
mental disorders, elderly or homeless persons with serious mental
illnesses and drug abuse/addictive disorders) to assess potential
risk factors for the co-occurrence of drug abuse/addiction and mental
disorders. In addition, data on patterns of symptoms, levels of
impairments, help-seeking behaviors, and treatment history are

Pharmacological interventions alone and in combination with
behavioral approaches may be examined.  Protocols may be developed
for detoxification, maintenance, and relapse prevention for specific
drugs of abuse when other comorbid conditions are present.  Drug-
medication, medication-medication, and medication-disease
interactions may be examined when pharmacotherapy is prescribed for
one or both of the addictive or mental disorders, as well as

Behavioral therapies (e.g., cognitive therapy, psychotherapy, family
therapy, counseling, motivational interventions) to treat clients
diagnosed with a drug use disorder plus one or more other co-
occurring mental disorder may be developed and piloted.  Fully
developed therapies may be tested for efficacy.  Behavioral
interventions may also be developed, piloted and tested to prevent
comorbid conditions prior to clinical diagnosis.

Approaches to minimize the harm associated with drug addiction and
comorbid mental disorders, including both pharmacological and
behavioral interventions, may be developed and piloted and tested for

The developmental stage of the child or adolescent with or at risk
for comorbid mental and addictive disorders is an important
prevention and treatment consideration.  The development, piloting,
and efficacy testing of preventive interventions and treatment
protocols specifically designed for children and adolescents at
particular developmental stages is needed.

Studies involving course and temporal relationships of illness as
individuals move from having a single disorder to comorbid disorders.
Such studies can be clinical or epidemiological in design.  The
effect of treatment can be used to observe change in course, severity
and impairment among the multiple disorders studied.

Specific financing and reimbursement policies, and cost- and
utilization-management strategies, and effects of resource/funding
limitations on aspects of prevention and treatment service delivery
and subsequent outcomes for populations afflicted with comorbid
mental and addictive disorders may be studied.  Also of interest are
questions regarding the effect of service delivery system variables
(e.g. organizational structure and environment, management and
treatment practices and philosophy, staffing patterns, and clinical
training and expertise of drug abuse and mental health providers) on
treatment outcome in these populations.

Studies assessing the prevention and treatment needs in this
population and the relationship of need to demand, access, and
service utilization.  In addition, studies to test assessment
strategies and interventions to overcome barriers to access to and
utilization of services.

Integration of models for delivery of drug abuse and mental health
services for clients with a drug use disorder and a comorbid mental
disorder warrant further study. Innovative approaches to prevention,
outreach, client assessment, case management, assertive community
treatment, managed care, family treatment and systems-of-referral
among available service providers may be studied with the aim of
increasing enrollment in and decreasing early withdrawal from
treatment.  A particular area of interest is the development of
appropriate referral systems between drug abuse/addiction and mental
health providers.

Therapeutic environments such as psychiatric outpatient, inpatient,
short-and long-term residential programs, as well as hospitals,
primary care clinics, social service agencies, and correctional
facilities may be evaluated for their effectiveness for clients with
specific comorbid conditions.

Impact of comorbid mental and addictive disorders on HIV/AIDS
requires research to address linkage of services, continuity of care,
service utilization management, matching services to client needs,
financing/cost constraints, and cost effectiveness and cost-benefits.
In addition, studies of the effects of disconnections of services
between mental health and drug abuse populations and also, drug abuse
populations and homeless programs are of interest.

Development of AIDS prevention/intervention techniques that maximize
adherence to risk reduction and prophylactic regimens across changes
in cognitive, emotional, and physical state related to drug abuse,
fluctuating psychiatric status and HIV disease stage.  These could
include the development of intervention approaches to change
behaviors of persons seen in primary care, drug abuse treatment or
mental health settings, or through community outreach.  In addition,
studies that examine the role of cognitive dysfunction and poor
psychosocial functioning on the development of drug abuse, mental
disorders and HIV infection are of interest.

Genetic epidemiologic research is needed to examine rates of mental
and drug abuse/addiction disorders in families to assess whether
comorbidity is attributable to a causal mechanism between the co-
occurring mental and drug abuse/addictive disorders or if each
disorder is a manifestation of similar underlying factors (genetic,
environmental, or a combination).

Case-control studies of biological, familial, or psychological
factors that distinguish those with both mental and drug
abuse/addictive disorders, those with either disorder alone, and
those with neither disorder.

Research into the development of statistical methods for the analysis
of the transmission of co-occurring mental and drug abuse/addictive

Development of clinical instruments to conduct broad-based
behavioral/environmental assessments of risk for HIV and associated
illnesses, e.g., tuberculosis, in comorbid mental disordered
populations of drug abusers.  In addition, clinical instruments
should be developed using novel dimensional, non-DSM IV, assessments
as well as brief methods of identification and assessment for field


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 new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations) which
have been in effect since 1990. The new policy contains some new
provisions that are substantially different from the 1990 policies.
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 reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume
23, Number 11.

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


Applications are to be submitted on the grant application form PHS
398 (rev. 9/91) 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 Office of Grants Information, Division of Research Grants,
National Institutes of Health, Westwood Building, Room 449, Bethesda,
MD 20892, telephone 301/710-0267.  The title and number of the
program announcement must be typed in Item 2a of face page of the

FIRST (R29) award applications must include at least three sealed
letters of reference attached to the face page of the original
application.  FIRST (R29) award applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or principal investigator could be included
with the application.

The completed original application and five legible copies must be
sent or delivered to:

Division of Research Grants
National Institutes of Health
6701 Rockledge Drive, Room 1040 - MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express or courier service)


Applications will be assigned on the basis of established Public
Health Service referral guidelines.  Applications that are complete
and responsive to the program announcement will be reviewed for
scientific and technical merit by a peer review group convened 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 receive, will be discussed, assigned a priority
score and receive a second level review by the appropriate national
advisory council.  R03 applications do not receive a second-level

Review Criteria

o  scientific, technical, or clinical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of proposed research;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

o  adequancy of plans to include both genders and minorities and
their subgroups as appropriate for the scientific goals of the
research.  Plans for the recruitment and retention of subjects will
also be evaluated.

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


Applications will compete for available funds with all other approved
applications.  The following will be considered in making funding
decisions:  quality of the proposed project as determined by peer
review, availability of funds, and program priority.


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

Direct inquiries regarding programmatic issues to:

Arthur MacNeill Horton, Jr., Ed.D.
Division of Clinical and Services Research
National Institute on Drug Abuse
5600 Fishers Lane, Room 10A-46
Rockville, MD  20857
Telephone:  (301) 443-6697
Email:  ah61x@nih.gov

Kathryn M. Magruder, M.P.H., Ph.D.
Division of Epidemiology and Services Research
National Institute of Mental Health
5600 Fishers Lane, Room 10C-06
Rockville, MD  20857
Telephone:  (301) 443-3364
Email:  kmagrude@aoamh2.ssw.dhhs.gov

Direct inquires regarding fiscal issues to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A-54
Rockville, MD  20857
Telephone:  (301) 443-6710
Email:  gf6s@nih.gov

Bruce Ringler
Grants Management Branch
National Institute of Mental health
5600 Fishers Lane, Room 7C-15
Rockville, MD  20857
Telephone:  (301) 443-2065


This program is described in the Catalog of Federal Domestic
Assistance No. 93.279.  Awards are made under authorization of
Section 301 of the Public Health Service Act (42 USC 241) and
administered under PHS policies and Federal Regulations at Title 42
CFR 52 "Grants for Research Projects," Title 45 CFR Part 74 and 92,
"Administration of Grants" and 45 CFR Part 46, "Protection of Human
Subjects."  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency

Sections of the Code of Federal Regulations are available in booklet
form from the U.S. Government Printing Office.  Grants must be
administered in accordance with the PHS Grants Policy Statement,
(rev. 10/90), which may be available from your office of sponsored


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