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

Demitri Papolos, John Hennen, Melissa S. Cockerham, Herbert M. Lachman

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalJournal of Affective Disorders
Volume99
Issue number1-3
DOIs
StatePublished - Apr 2007

Fingerprint

Genetic Linkage
Bipolar Disorder
Siblings
Statistical Factor Analysis
Inborn Genetic Diseases
Neurobiology
Executive Function
Principal Component Analysis
Aggression
Fear
Surveys and Questionnaires
Sleep
Research Design
Multivariate Analysis
Anxiety
Interviews
Research

Keywords

  • Aggression
  • Anxiety
  • Behavioural phenotype
  • Child Bipolar Questionnaire
  • Childhood-onset bipolar disorder
  • Pediatric bipolar disorder
  • Sib-pair concordance

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Behavioral Neuroscience
  • Biological Psychiatry
  • Neurology
  • Psychology(all)

Cite this

@article{fe09634af9ac4c38995d65cc51ca3669,
title = "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",
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.",
keywords = "Aggression, Anxiety, Behavioural phenotype, Child Bipolar Questionnaire, Childhood-onset bipolar disorder, Pediatric bipolar disorder, Sib-pair concordance",
author = "Demitri Papolos and John Hennen and Cockerham, {Melissa S.} and Lachman, {Herbert M.}",
year = "2007",
month = "4",
doi = "10.1016/j.jad.2006.08.014",
language = "English (US)",
volume = "99",
pages = "27--36",
journal = "Journal of Affective Disorders",
issn = "0165-0327",
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TY - JOUR

T1 - A strategy for identifying phenotypic subtypes

T2 - 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

AU - Papolos, Demitri

AU - Hennen, John

AU - Cockerham, Melissa S.

AU - Lachman, Herbert M.

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

KW - Aggression

KW - Anxiety

KW - Behavioural phenotype

KW - Child Bipolar Questionnaire

KW - Childhood-onset bipolar disorder

KW - Pediatric bipolar disorder

KW - Sib-pair concordance

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