title: A family study of manic-depressive (bipolar I) disease. Is it a distinct illness separable from primary unipolar depression?
abstract: OBJECTIVE
  To determine whether bipolar I illness is autonomous or part of a multifactorial continuum with unipolar depression. In this study, we compare familial bipolar I illness and depression among three groups: probands with bipolar I disorder; probands with primary unipolar disorder; and controls. We also examine a continuum of severity between psychotic and nonpsychotic patients with bipolar I disorder. Considerable data suggest that bipolar I illness is distinct from unipolar illness as regards epidemiology, familial psychiatric illness, course, response to treatment, and biologic findings.
  
  
  METHODS
  Probands were separated into bipolar I and primary unipolar depressive groups. Personally interviewed family members of these patients were compared on variables of bipolar illness or schizoaffective mania and unipolar or schizoaffective depression. A personally examined control group was compared with the relatives of the two proband groups. Similar analyses were performed using data obtained by a systematic family history method. For the same familial variables, psychotic and nonpsychotic manic probands were compared.
  
  
  RESULTS
  Familial mania is more frequent in families of patients with bipolar disease than in controls or in families of patients with primary unipolar disorder. The latter two groups did not differ in amount of mania. Unipolar depressive illness or schizoaffective depression was higher in families of probands with bipolar and unipolar disorder than in controls. Probands with bipolar disease separated into those who had psychotic symptoms (including schizoaffective mania) and no psychotic symptoms did not differ from each other in risk for familial mania or depression.
  
  
  CONCLUSIONS
  Bipolar I illness is a separate illness from primary unipolar illness because of an increase in familial mania. Patients with primary unipolar disease and controls show the same amount of familial mania. Lack of an increase in familial illness according to the severity of bipolar disease is against an affective continuum.
authors.affiliation: National Institute of Mental Health Collaborative Program on the Psychobiology of Depression--Clinical Studies, Bethesda, Md, USA.
authors.forename: G
authors.initials: G
authors.lastname: Winokur
authors.forename: W
authors.initials: W
authors.lastname: Coryell
authors.forename: M
authors.initials: M
authors.lastname: Keller
authors.forename: J
authors.initials: J
authors.lastname: Endicott
authors.forename: A
authors.initials: A
authors.lastname: Leon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D002648:Child; D015897:Comorbidity; D003866:Depressive Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D003937:Diagnosis, Differential; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D012720:Severity of Illness Index