The Collaborative Depression Study's aims have been to clarify the nosology of the affective disorders by using clinically ascertained samples of probands and their first degree relatives to investigate the clinical features, course, outcome, including mortality, personality, family history including temporal trends, stability of diagnosis, and genetics of affective disorders. The first two basic aims of this application is to develop, advance and generalize our major findings by continuing proband and relative follow-up to 15 years and 13 years respectively and by including DSM-lll-R diagnosis where possible. The second is to expand genetics, personality, and outcome: (1) in genetics, to systematically map the entire genome using restriction fragment length polymorphisms, to map using candidate probes, and to identify genetic linkage between DNA probes within unipolar and bipolars disorders; (2) in personality, to investigate how DSM-lll-R personality disorders effect the course and outcome of affective disorders, how affective disorders effect the assessment of personality disorders including their stability, to detail relationship between personality disorders and self-reported personality traits, and finally to investigate transmission of personality disorders within families including possible co-transmission with affective disorder; (3) for outcome to record somatic disorders, physical disability and general functioning in a manner permitting comparison with national normative data. To insure quality and uniformity of data, raters will be trained to use the SADS-L (Modified) and the Personality Disorder Examination (PDE) prior to relative follow-up. Test-retest reliability for the PDE will be measured during the second year. To obtain the data itself, we will continue yearly proband follow-up adding the Medical Outcome Studies-Short Form (MOS-SF), and at the initial interview of the grant period conducting the PDE. For those affectively ill, a second PDE will be administered when remitted. At the second proband interview, diagnostic information to include DSM-lll-R criteria for substance abuse, anxiety, anxiety disorders, and others will be added. All relatives, spouses and controls will be administered a blind SADS-L, interval SADS, PDE, and MOS-SF during their 13 year follow-up (T3). A 50% subset with and without personality disorders will have a second blind PDE 2 years after the initial PDE. Pedigrees will be extended with diagnoses established with SADS-L interviews and blood drawn for DNA extraction during T3 relative follow-up. Analyses of data will be done as appropriate to the center's interest. Genetic analyses will be done by St. Louis and Iowa. Morbidity and mortality analyses will be done by Chicago. Course and follow-up analyses will be centered in Boston. Psychiatric co-morbidity studies will be centered in New York.
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