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: dwynne1@nih.gov .
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