A strategy for identifying phenotypic subtypes: concordance of symptom dimensions between sibling pairs who met screening criteria for a genetic linkage study of childhood-onset bipolar disorder using the Child Bipolar Questionnaire.
BACKGROUND
Specific symptom dimensions have been used to establish phenotypic subgroups in recent genetic studies of bipolar disorder. In preparation for a genetic linkage study of childhood-onset bipolar disorder (COBPD), we conducted an exploratory analysis of the concordance of prominent symptom dimensions between sibling pairs (N=260) who screened positive for COBPD. This report presents data on the potential usefulness of these dimensions in genotyping.


METHODS
A principal components factor analysis was conducted on the symptoms of 2795 children who screened positive for COBPD on the Child Bipolar Questionnaire (CBQ). The resulting factors were used in a concordance analysis between 260 proband/sibling pairs and 260 proband/matched comparison pairs.


RESULTS
Ten factors were extracted. The strongest concordance coefficients (rho) between probands and siblings, and the widest contrasts between proband/sibling vs. proband/comparison pairs, were for Factor 9 (Fear of harm), Factor 5 (Aggression), Factor 10 (Anxiety), Factor 4 (Sensory sensitivity), Factor 6 (Sleep-wake cycle disturbances), and Factor 2 (Attention/Executive function deficits). Based on factor loadings and multivariate analyses, CBQ items were selected for a "Core Index" subscale that had a robust concordance estimate in the sibpair group (rho=0.514, 95% CI 0.450-0.577) as compared to the proband-matched comparison group (rho=0.093, 95% CI 0.008 to 0.178).


CONCLUSIONS
Research diagnostic interviews (K-SADS P/L) were conducted to confirm bipolar diagnosis in only a subsample (N=100) of the children whose data were used for the concordance analysis.


CONCLUSIONS
Our data suggest a profile of heritable clinical dimensions in addition to classic mood symptomatology in COBPD. These features may represent a more homogeneous phenotypic subtype of COBPD that may prove more useful for delineating the neurobiology and genetics of the disorder than standard diagnostic models.
Papolos
Demitri
D
The Juvenile Bipolar Research Foundation, Research Department, 550 Ridgewood Road, Maplewood, NJ 07040, USA. dpapolos@jbrf.org
Hennen
John
J
Cockerham
Melissa S
MS
Lachman
Herbert
H
D000293:Adolescent; D000374:Aggression / Q000523:psychology; D001008:Anxiety Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002648:Child; D002653:Child Behavior Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D015897:Comorbidity; D005239:Fear; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D008403:Mass Screening; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D035781:Siblings