Papolos Demitri, Hennen John, Cockerham Melissa S, Lachman Herbert
The Juvenile Bipolar Research Foundation, Research Department, 550 Ridgewood Road, Maplewood, NJ 07040, USA.
J Affect Disord. 2007 Apr;99(1-3):27-36. doi: 10.1016/j.jad.2006.08.014. Epub 2006 Oct 16.
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.
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.
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).
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.
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.
在近期双相情感障碍的遗传学研究中，特定症状维度已被用于建立表型亚组。为开展儿童期起病双相情感障碍（COBPD）的遗传连锁研究做准备，我们对COBPD筛查呈阳性的同胞对（N = 260）之间突出症状维度的一致性进行了探索性分析。本报告展示了这些维度在基因分型中的潜在有用性的数据。
对在儿童双相情感问卷（CBQ）上COBPD筛查呈阳性的2795名儿童的症状进行主成分因子分析。所得因子用于260对先证者/同胞对与260对先证者/匹配对照对之间的一致性分析。
提取出十个因子。先证者与同胞之间最强的一致性系数（rho），以及先证者/同胞对与先证者/对照对之间最大的差异，出现在因子9（害怕受伤害）、因子5（攻击性）、因子10（焦虑）、因子4（感觉敏感）、因子6（睡眠 - 觉醒周期紊乱）和因子2（注意力/执行功能缺陷）上。基于因子载荷和多变量分析，为一个“核心指标”子量表选择了CBQ项目，该子量表在同胞对组中的一致性估计很强（rho = 0.514，95% CI 0.450 - 0.577），而在与先证者匹配的对照对组中（rho = 0.093，95% CI 0.008至0.178）。
仅对用于一致性分析的数据的儿童子样本（N = 100）进行了研究诊断访谈（K - SADS P/L）以确认双相情感障碍诊断。
我们的数据表明，除了COBPD的经典情绪症状学外，还存在可遗传的临床维度特征。这些特征可能代表了COBPD一种更同质的表型亚型，与标准诊断模型相比，可能在描绘该疾病的神经生物学和遗传学方面更有用。
