{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:01:02Z","timestamp":1791896462651,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2001,8,27]],"date-time":"2001-08-27T00:00:00Z","timestamp":998870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[2001,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early\u2010onset MDD (RE\u2010MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE\u2010MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (\u2265\u20092 episodes), early\u2010onset (\u2264\u200925 years), nonpsychotic, unipolar MDD (RE\u2010MDD), and included 407 first\u2010degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first\u2010degree relatives and a quarter of extended relatives of RE\u2010MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MDD reflected by age at onset and number of episodes attenuated with increasing familial\/genetic distance from the proband. A substantial fraction of RE\u2010MDD probands and their first\u2010degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE\u2010MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several\u2010fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE\u2010MDD probands. However, the rank order of the three most common causes of death\u2014heart disease, cancer, and stroke\u2014remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE\u2010MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.1554","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T04:51:41Z","timestamp":1030251101000},"page":"690-699","source":"Crossref","is-referenced-by-count":64,"title":["Malignancy of recurrent, early\u2010onset major depression: A family study"],"prefix":"10.1002","volume":"105","author":[{"given":"George S.","family":"Zubenko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy N.","family":"Zubenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duane 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