title: Mood-incongruent psychosis in bipolar disorder: conditional linkage analysis shows genome-wide suggestive linkage at 1q32.3, 7p13 and 20q13.31.
abstract: OBJECTIVE
  The majority of research into functional psychosis has proceeded under the assumption that schizophrenia and bipolar disorder are distinct entities with separate underlying disease processes and treatments. This view has been increasingly challenged in both clinical and genetic studies. Findings in recent association studies at two specific genes suggest that the occurrence of mood-incongruent psychotic features may indicate a relatively homogeneous subset of the bipolar phenotype. We examined this hypothesis.
  
  
  METHODS
  Caucasian affected individuals were ascertained from Europe (the United Kingdom, the Republic of Ireland, Germany, Italy and Andalusia). Consensus best-estimate diagnoses were assigned by two independent raters according to all available information. There was no cross-site evaluation of inter-rater reliability. Families multiply affected by bipolar spectrum mood disorder were selected, comprising 383 affected relative pairs. Individuals were considered to be affected if they were diagnosed with DSM-IV bipolar I disorder or schizoaffective disorder, bipolar type. Multipoint, affected relative pair covariate linkage analysis was performed.
  
  
  RESULTS
  Significant familiality of incongruent psychosis was observed [intra-class correlation coefficient (ICC) = 0.309; p = 0.001, one-tail]. Covariate linkage analysis provided three regions with genome-wide suggestive evidence for linkage on chromosomes 1q32.3 (LOD = 4.15, expected 0.12 times per genome scan), 7p13 (LOD = 3.32) and 20q13.31 (LOD = 2.98). No region in our analysis met criteria for genome-wide significance.
  
  
  CONCLUSIONS
  Our results provide molecular support for the hypothesis that genes may exist for specific forms of bipolar illness, dependent on the presence or absence of incongruent psychosis. Our findings suggest that researchers should take account of mood-congruence/incongruence of psychotic features in studies of bipolar disorder.
authors.affiliation: Department of Psychological Medicine, The Henry Wellcome Building for Biomedical Research in Wales, Cardiff, CF14 4XN, UK.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Hamshere
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Rami Abou
authors.initials: RA
authors.lastname: Jamra
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Guillermo
authors.initials: G
authors.lastname: Orozco y Diaz
authors.forename: Fermin
authors.initials: F
authors.lastname: Mayoral
authors.forename: Fabio
authors.initials: F
authors.lastname: Rivas
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Peter A
authors.initials: PA
authors.lastname: Holmans
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
mesh_terms: D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics; D006113:United Kingdom