title: Characteristics of Bipolar I patients grouped by externalizing disorders.
abstract: BACKGROUND
  Bipolar disorder co-occurs with a number of disorders with externalizing features. The aim of this study is to determine whether Bipolar I (BPI) subjects with comorbid externalizing disorders and a subgroup with externalizing symptoms prior to age 15 have different clinical features than those without externalizing disorders and whether these could be attributed to specific genetic variations.
  
  
  METHODS
  A large cohort (N=2505) of Bipolar I subjects was analyzed. Course of illness parameters were compared between an Externalizing Group, an Early-Onset Subgroup and a Non-Externalizing Group in the Discovery sample (N=1268). Findings were validated using an independent set of 1237 BPI subjects (Validation sample). Genetic analyses were carried out.
  
  
  RESULTS
  Subjects in the Externalizing Group (and Early-Onset Subgroup) tended to have a more severe clinical course, even in areas specifically related to mood disorder such as cycling frequency and rapid mood switching. Regression analysis showed that the differences are not completely explainable by substance use. Genetic analyses identified nominally associated SNPs; calcium channel genes were not enriched in the gene variants identified.
  
  
  CONCLUSIONS
  Validation in independent samples is needed to confirm the genetic findings in the present study.
  
  
  CONCLUSIONS
  Our findings support the presence of an externalizing disorder subphenotype within BPI with greater severity of mood disorder and possible specific genetic features.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shanker
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Niculescu
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: jnurnber@iupui.edu.
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect; D017668:Age of Onset; D000368:Aged; D001714:Bipolar Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012720:Severity of Illness Index; D012919:Social Behavior; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: Bipolar disorder; Comorbidity; Early onset; Externalizing disorders; Genome-Wide Association Study (GWAS)
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