title: Age at Onset of Bipolar Disorder Related to Parental and Grandparental Illness Burden.
abstract: OBJECTIVE
  The age at onset of bipolar disorder varies greatly in different countries and continents. The association between load of family history of psychiatric illness and age at onset has not been adequately explored.
  
  
  METHODS
  979 outpatients with bipolar disorder (from 4 sites in the United States and 3 in the Netherlands and Germany) gave informed consent and completed a questionnaire about their demographics, age at onset of illness, and family history of unipolar and bipolar disorder, alcohol and substance abuse comorbidity, suicide attempts, and "other" illnesses in their parents, 4 grandparents, and any offspring. We examined how the parental and grandparental burden of these illnesses related to the age at onset of the patients' bipolar disorder.
  
  
  RESULTS
  The burden of family psychiatric history was strongly related to an earlier age at onset of illness in both US and European patients (F₃,₉₀₆ = 35.42, P < .0001). However, compared to the Europeans, patients in the United States had both more family history of most difficulties and notably earlier age at onset. Earlier age at onset was associated with a greater illness burden in the patient's offspring (t₅₆₈ = 4.1, P < .0001).
  
  
  CONCLUSIONS
  More parental and grandparental psychiatric illness was associated with an earlier age at onset of bipolar disorder, which is earlier in the United States compared with Europe and is strongly related to a poor long-term prognosis. This apparent polygenic contribution to early onset deserves further study and therapeutic attempts at ameliorating the transgenerational impact.
authors.affiliation: Bipolar Collaborative Network, 5415 West Cedar Ln, Ste 201B, Bethesda, MD 20814. robert.post@speakeasy.net.|Bipolar Collaborative Network, Bethesda, Maryland, USA.|Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, DC, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.|Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, California, USA.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Altshuler
authors.affiliation: Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Kupka
authors.affiliation: Lindner Center of HOPE, Mason, Ohio, USA.|Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, Ohio, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: Department of Psychiatry, Mayo Clinic, Rochester, Michigan, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Bipolar Collaborative Network, Bethesda, Maryland, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rowe
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA.|VA Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.affiliation: Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.|Lindner Center of HOPE, Mason, Ohio, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Keck
authors.affiliation: Bipolar Collaborative Network, Bethesda, Maryland, USA.
authors.forename: Gabriele S
authors.initials: GS
authors.lastname: Leverich
authors.affiliation: University Medical Center, University of Groningen, the Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D017281:Cost of Illness; D003431:Cross-Cultural Comparison; D005260:Female; D005858:Germany; D000066502:Grandparents / Q000523:psychology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010290:Parents / Q000523:psychology*; D011379:Prognosis; D011795:Surveys and Questionnaires; D014481:United States; D055815:Young Adult