NATIONAL INSTITUTE OF MENTAL HEALTH GENETICS INITIATIVE 

NIH Guide, Volume 25, Number 23, July 12, 1996

 

P.T. 34



Keywords:

  Genetics 

  Demography 

  Mental Disorders 

 

National Institute of Mental Health

 

Given the major public health implications of identifying genes

responsible for severe neuropsychiatric disorders, the National

Institute of Mental Health (NIMH) has funded a Genetics Initiative to

establish a national resource of demographic, clinical, diagnostic,

and genetic data from individuals with bipolar (BP) disorder,

schizophrenia (SZ), or Alzheimer disease (AD), in order to aid

researchers in identifying etiologic factors responsible for these

disorders.

 

This notice announces the availability of clinical/diagnostic data

and DNA samples to qualified investigators studying the genetics of

SZ or BP.  Files of demographic and diagnostic variables necessary

for genetic analysis with accompanying documentation, access to DNA

samples, a code manual listing additional clinical and demographic

data, and pedigree drawings prepared using the CYRILLIC program, are

available.  Comparable data for the AD Genetics Initiative have been

available to qualified investigators since July 1, 1995 (NIH Guide,

Vol. 24, No. 23, June 23, 1995).  Descriptive information on the BP,

SZ, and AD samples are provided on the World Wide Web at http://www-

srb.nimh.nih.gov/gi.html.

 

Data being collected include a psychiatric assessment using the

Diagnostic Interview for Genetic Studies (DIGS).  The DIGS is a

polydiagnostic interview that permits the determination of affective

and schizophrenia core and spectrum illnesses in multiple diagnostic

systems.  A number of comorbid disorders are also evaluated in the

DIGS, including alcohol and substance abuse disorders, and their

chronological relationship to the onset of schizophrenic or affective

spectrum illnesses is determined.  The DIGS also includes sections to

assess general and psychiatric medical history, demographic aspects,

and additional clinical information on symptoms, suicidality, and

course of illness.

 

The diagnostic process in the NIMH SZ and BP Genetics Initiative

includes a systematic and comprehensive examination of multiple

sources of available information obtained from relatives, medical

records, clinical notes and other diagnostic information, and direct

interviews. Resolution of discrepancies that occur among these data

sources are resolved by a final best-estimate diagnostic procedure

that involves at least two senior clinicians.  It is anticipated that

subjects will be followed longitudinally to track potential changes

in diagnoses, thus avoiding the false-positive diagnoses that are a

major pitfall of genetic linkage studies.

 

Schizophrenia

 

Families with SZ and related spectrum disorders are identified via

cooperative agreements to Columbia University, Harvard University,

and Washington University. Data collection utilizes an agreed-upon

protocol that includes uniform DIGS assessment, final best estimate

diagnoses, and shared rules for extension of pedigrees through

affected members.  Pedigrees have been ascertained in which there are

at least two affected individuals who are biologically related as

first-degree relatives.  In systematic ascertainment, an affected

individual with DSM-III-R SZ or schizoaffective disorder - depressive

type (SAD) is identified through systematic screening of patients

within a clinical population.  Then, if the affected individual

initially identified has at least one living first-degree relative

with SZ or SAD, the pedigree is targeted for further examination.

The affected individual initially identified and each one of these

relatives constitutes a pair.  A pedigree is enrolled in the study if

it contains at least one pair where one member is diagnosed with SZ

and the other is diagnosed with SZ or SAD.  Some nonsystematically

ascertained pedigrees are enrolled at one site if all rules for

systematic ascertainment are met and the pedigree contains at least

one additional first- or second- degree relative with SZ, SAD, or

schizotypal personality disorder (determined through direct

interview). Nonsystematically ascertained pedigrees are recruited

from a variety of sources, e.g., clinical referrals, media

advertising, and local chapters of the Alliance for the Mentally Ill.

Overall, approximately 88 percent of families have been

systematically ascertained. Pedigrees are sequentially extended

through first-degree relatives of specific individuals with specific

diagnoses.

 

Bipolar Disorder

 

Families with BP disorder and related spectrum disorders are

identified via cooperative agreements to Indiana University, Johns

Hopkins University, and Washington University. A fourth site, the

Clinical Neurogenetics Branch of the NIMH Intramural Research

Program, participates but is not supported via the U01 grant

mechanism.  Data collection utilizes an agreed-upon protocol which

includes uniform DIGS assessment, final best estimate diagnoses, and

shared rules for extension of pedigrees through affected members.

Pedigrees have been ascertained in which there are at least two

affected individuals who are biologically related as first-degree

relatives.  Pedigrees are sequentially extended through first-degree

relatives of specific individuals with specific diagnoses.  Pedigrees

in which both parents of the proband have SAB or BPI disorder are

excluded.

 

In systematic ascertainment, an affected individual with DSM-III-R

bipolar I (BPI) disorder is identified through systematic screening

of patients within a clinical population.  Then, if the affected

individual initially identified has at least one-living first degree

relative with BPI disorder or schizoaffective disorder - bipolar type

(SAB), the pedigree is targeted for further examination. A

nonsystematically ascertained pedigree is enrolled in the study if it

contains at least four affecteds.  Two of these affecteds form a pair

where one member is diagnosed with BPI disorder and the other is

diagnosed with BPI disorder or SAB. These subjects may be

first-degree relatives or they may be second-degree relatives who are

connected through a subject with bipolar II (BPII) disorder as

defined by the Research Diagnostic Criteria (RDC).  Two additional

ill family members with BPI disorder, SAB, BPII disorder, or

recurrent unipolar depressive disorder as defined by the RDC are

required.  Pedigrees are recruited from a variety of sources, e.g.,

clinical referrals, media advertising, and local chapters of the

Alliance for the Mentally Ill. Overall, approximately 60 percent of

families have been systematically ascertained.

 

Access to Data and DNA

 

Clinical information and DNA will be distributed only to experienced

and qualified investigators conducting research on the genetics of

AD, SZ or BP at recognized biomedical research facilities.

Interested investigators may request access to the data by sending a

request to Debra Wynne, at the address listed under INQUIRIES.

Investigators without funding under a peer-reviewed NIMH research

grant application to analyze these data must purchase DNA samples

from the NIMH Genetics Initiative Cell Repository at a cost of $50

per subject for a 50 microgram vial (DNA is shipped only in 50

microgram vials).

 

Any and all data obtained by an experienced and qualified

investigator cannot be transferred in any manner, with or without

charge, to anyone not under the direct supervision of that

investigator, without the expressed written permission of the NIMH.

 

INQUIRIES

 

Inquiries regarding these data and requests may be directed to:

 

Debra Wynne, M.S.W.

Division of Clinical and Treatment Research

National Institute of Mental Health

5600 Fishers Lane, Room 18C-14

Rockville, MD  20857

Telephone:  (301) 443-3527

FAX:  (301) 443-6000

Email:  [email protected]

 

.

Return to 1996 Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)