title: Familial aggregation of illness chronicity in recurrent, early-onset major depression pedigrees.
abstract: OBJECTIVE
  The authors used a large sample collected for genetic studies to determine whether a chronic course of illness defines a familial clinical subtype in major depressive disorder.
  
  
  METHODS
  A measure of lifetime chronicity of depressive symptoms (substantial mood symptoms most or all of the time) was tested for familial aggregation in 638 pedigrees from the Genetics of Recurrent Early-Onset Depression (GenRED) project.
  
  
  RESULTS
  In subjects with chronic depression, the mean age at illness onset was lower and rates of attempted suicide, panic disorder, and substance abuse were higher than among those with nonchronic depression. Chronicity was assessed in 37.8% of affected first-degree relatives of probands with chronic depression and in 20.2% of relatives of probands with nonchronic depression. Analysis using the generalized estimating equation model yielded an odds ratio of 2.52 (SE=0.39, z=6.02, p<0.0001) for the likelihood of chronicity in a proband predicting chronicity in an affected relative. With stratification by proband age at illness onset, the odds ratio for chronicity in relatives by proband chronicity status was 6.17 (SE=2.09, z=5.35, p<0.0001) in families of probands whose illness onset was before age 13 and 1.92 (SE=0.34, z=3.72, p<0.0001) in families of probands whose illness started at age 13 or later.
  
  
  CONCLUSIONS
  These findings suggest that chronicity of depressive symptoms is familial, especially in preadolescent-onset illness. Chronicity is also associated with other indicators of illness severity in recurrent, early-onset major depression. Further study using chronicity as a subtype in the genetic analysis of depressive illness is warranted. Refinement of the definition of chronicity in depressive illness may increase the power of such studies.
authors.affiliation: Johns Hopkins Hospital, Meyer 3-181, 600 North Wolfe St., Baltimore, MD 21287, USA. fmondimo@jhmi.edu
authors.forename: Francis M
authors.initials: FM
authors.lastname: Mondimore
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zandi
authors.forename: Dean F
authors.initials: DF
authors.lastname: Mackinnon
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
authors.forename: Erin B
authors.initials: EB
authors.lastname: Miller
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Crowe
authors.forename: William A
authors.initials: WA
authors.lastname: Scheftner
authors.forename: Diana H
authors.initials: DH
authors.lastname: Marta
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Levinson
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: Murphy-Ebenez
authors.forename: J Raymond
authors.initials: JR
authors.lastname: Depaulo
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002908:Chronic Disease; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D016584:Panic Disorder / Q000175:diagnosis / Q000453:epidemiology; D010375:Pedigree; D012107:Research Design; D012720:Severity of Illness Index; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000453:epidemiology; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data; D009626:Terminology as Topic