title: Increases in multiple psychiatric disorders in parents and grandparents of patients with bipolar disorder from the USA compared with The Netherlands and Germany.
abstract: OBJECTIVE
  We previously found that compared with Europe more parents of the USA patients were positive for a mood disorder, and that this was associated with early onset bipolar disorder. Here we examine family history of psychiatric illness in more detail across several generations.
  
  
  METHODS
  A total of 968 outpatients (average age 41) with bipolar disorder from four sites in the USA and three in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic and family history information on a patient questionnaire. Family history of psychiatric illness (bipolar disorder, unipolar depression, suicide attempt, alcohol abuse, substance abuse, and other illness) was collected for each parent, four grandparents, siblings, and children.
  
  
  RESULTS
  Parents of the probands with bipolar disorder from the USA compared with Europe had a significantly higher incidence of both unipolar and bipolar mood disorders, as well as each of the other psychiatric conditions listed above. With a few exceptions, this burden of psychiatric disorders was also significantly greater in the grandparents, siblings, and children of the USA versus European patients.
  
  
  CONCLUSIONS
  The increased complexity of psychiatric illness and its occurrence over several generations in the families of patients with bipolar disorder from the USA versus Europe could be contributing to the higher incidence of childhood onsets and greater virulence of illness in the USA compared with Europe. These data are convergent with others suggesting increased both genetic and environmental risk in the USA, but require replication in epidemiologically-derived populations with data based on interviews of the family members.
authors.affiliation: aBipolar Collaborative Network, Bethesda, Maryland bDepartment of Psychiatry and Behavioral Sciences, George Washington University, Washington, District of Columbia cDepartment of Psychiatry and Behavioral Neuroscience dDepartment of Psychiatry and Behavioral Neuroscience, Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati eLindner Center of HOPE, Mason, Ohio fDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California gDepartment of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles hDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine iV.A. Palo Alto HealthCare System, Palo Alto, California jDepartment of Psychiatry, Mayo Clinic, Rochester, Michigan, USA kDepartment of Psychiatry, VU University Medical Center, Amsterdam lDepartment of Psychiatry, University Medical Center, University of Groningen, Groningen, The Netherlands mDepartment of Psychiatry and Psychotherapy, Christian Doppler Klink, Paracelsus Medical University Salzburg, Austria.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
authors.forename: Gabriele S
authors.initials: GS
authors.lastname: Leverich
authors.forename: Ralph
authors.initials: R
authors.lastname: Kupka
authors.forename: Paul E
authors.initials: PE
authors.lastname: Keck
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.forename: Lori L
authors.initials: LL
authors.lastname: Altshuler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: Michael
authors.initials: M
authors.lastname: Rowe
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
mesh_terms: D000328:Adult; D017668:Age of Onset; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics / Q000523:psychology; D005858:Germany / Q000453:epidemiology; D000066502:Grandparents / Q000523:psychology*; D006801:Humans; D015994:Incidence; D001523:Mental Disorders / Q000453:epidemiology* / Q000235:genetics / Q000523:psychology; D009426:Netherlands / Q000453:epidemiology; D010290:Parents / Q000523:psychology*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology