Abstract
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. Method 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). Limitations 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.
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