Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33.
OBJECTIVE
Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features.


METHODS
Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed.


RESULTS
Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance.


CONCLUSIONS
Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.
Goes
Fernando S
FS
Johns Hopkins Hospital, 600 North Wolfe St., Meyer 4-119, Baltimore, MD 21287-7419, USA.
Zandi
Peter P
PP
Miao
Kuangyi
K
McMahon
Francis J
FJ
Steele
Jo
J
Willour
Virginia L
VL
Mackinnon
Dean F
DF
Mondimore
Francis M
FM
Schweizer
Barbara
B
Nurnberger
John I
JI
Rice
John P
JP
Scheftner
William
W
Coryell
William
W
Berrettini
Wade H
WH
Kelsoe
John R
JR
Byerley
William
W
Murphy
Dennis L
DL
Gershon
Elliot S
ES
Bipolar Disorder Phenome Group
Depaulo
J Raymond
JR
McInnis
Melvin G
MG
Potash
James B
JB
D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D015331:Cohort Studies; D003702:Delusions / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D005192:Family Health; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006212:Hallucinations / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics; D012720:Severity of Illness Index