title: Illnesses in siblings of US patients with bipolar disorder relate to multigenerational family history and patients severity of illness.
abstract: Patients with bipolar disorder from the US have more early-onset illness and a greater familial loading for psychiatric problems than those from the Netherlands or Germany (abbreviated here as Europe). We hypothesized that these regional differences in illness burden would extend to the patients siblings.
  
  
  
  Outpatients with bipolar disorder gave consent for participation in a treatment outcome network and for filling out detailed questionnaires. This included a family history of unipolar depression, bipolar disorder, suicide attempt, alcohol abuse/dependence, drug abuse/dependence, and "other" illness elicited for the patients' grandparents, parents, spouses, offspring, and siblings. Problems in the siblings were examined as a function of parental and grandparental problems and the patients' adverse illness characteristics or poor prognosis factors (PPFs).
  
  
  
  Each problem in the siblings was significantly (p<0.001) more prevalent in those from the US than in those from Europe. In the US, problems in the parents and grandparents were almost uniformly associated with the same problems in the siblings, and sibling problems were related to the number of PPFs observed in the patients.
  
  
  
  Family history was based on patient report.
  
  
  
  Increased familial loading for psychiatric problems extends through 4 generations of patients with bipolar disorder from the US compared to Europe, and appears to "breed true" into the siblings of the patients. In addition to early onset, a variety of PPFs are associated with the burden of psychiatric problems in the patients' siblings and offspring. Greater attention to the multigenerational prevalence of illness in patients from the US is indicated.
authors.affiliation: Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington D.C., 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, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, 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, OH, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Kupka
authors.affiliation: Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: Department of Psychiatry, Mayo Clinic, Rochester, MI, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Bipolar Collaborative Network, Bethesda, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rowe
authors.affiliation: Department of Psychiatry and Psychotherapy, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.affiliation: Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Keck
authors.affiliation: University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000523:psychology; D017281:Cost of Illness; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D012720:Severity of Illness Index; D035781:Siblings / Q000523:psychology*; D018454:Spouses; D019966:Substance-Related Disorders; D013406:Suicide, Attempted / Q000523:psychology; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
keywords: Alcohol abuse/dependence; Anxiety disorder; Depression; Illness differences across countries; Substance abuse/dependence; Suicide attempts; Transgenerational vulnerability