Arbona-Lampaya Alejandro, Sung Heejong, D'Amico Alexander, Knowles Emma E M, Besançon Emily K, Freifeld Ally, Lacbawan Ley, Lopes Fabiana, Kassem Layla, Nardi Antonio E, McMahon Francis J
Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA; School of Medicine, University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico.
Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
J Affect Disord. 2025 Mar 1;372:394-401. doi: 10.1016/j.jad.2024.12.030. Epub 2024 Dec 10.
Bipolar disorder (BD) presents with a wide range of symptoms that vary among relatives, casting doubt on categorical illness models. To address this uncertainty, we investigated the heritability and genetic relationships between categorical and dimensional models of BD in a family sample.
This retrospective study included participants (n = 397 Females, n = 329 Males, mean age 47 yr) in the Amish-Mennonite Bipolar Genetics (AMBiGen) study from North and South America that were assigned categorical mood disorder diagnoses ("narrow" or "broad") by structured psychiatric interview and completed the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of manic symptoms and associated impairment. MDQ-dimensions were analyzed by Principal Component Analysis (PCA). Heritability and genetic overlaps between categorical diagnoses and MDQ-dimensions were estimated with SOLAR-ECLIPSE within 432 genotyped participants.
Individuals diagnosed with BD (n = 124) endorsed more MDQ items (61 %) than those with other mood disorders (26 %) or with no mood disorder (9 %), as expected. PCA suggested a three-component model for the MDQ, capturing 60 % of the variance. Heritability of the MDQ and its principal components was significant but modest (20-30 %, p < 0.001). Genetic correlations between MDQ measures and categorical diagnoses (ρG = 0.62-1.0; p < 0.001) were stronger than phenotypic correlations (ρP = 0.11-0.58; p < 0.001).
Recruitment through probands with BD resulted in increased prevalence of BD in this sample, limiting generalizability. Unavailable genetic data reduced sample size for some analyses.
Findings support a genetic continuity between dimensional and categorical models of BD and suggest that the MDQ is a useful phenotype measure for genetic studies of BD.
双相情感障碍（BD）呈现出广泛的症状，这些症状在亲属之间存在差异，这使得对分类疾病模型产生了怀疑。为了解决这种不确定性，我们在一个家庭样本中研究了BD分类模型和维度模型之间的遗传力及遗传关系。
这项回顾性研究纳入了来自北美和南美的阿米什 - 门诺派双相情感障碍遗传学（AMBiGen）研究的参与者（n = 397名女性，n = 329名男性，平均年龄47岁），这些参与者通过结构化精神病学访谈被给予分类情绪障碍诊断（“狭义”或“广义”），并完成了情绪障碍问卷（MDQ），该问卷评估躁狂症状的终生病史及相关损害。MDQ维度通过主成分分析（PCA）进行分析。在432名基因分型参与者中，使用SOLAR - ECLIPSE估计分类诊断与MDQ维度之间的遗传力和遗传重叠。
正如预期的那样，被诊断为BD的个体（n = 124）认可的MDQ项目（61%）比患有其他情绪障碍的个体（26%）或没有情绪障碍的个体（9%）更多。主成分分析表明MDQ存在一个三成分模型，可解释60%的方差。MDQ及其主要成分的遗传力显著但适中（20 - 30%，p < 0.001）。MDQ测量与分类诊断之间的遗传相关性（ρG = 0.62 - 1.0；p < 0.001）强于表型相关性（ρP = 0.11 - 0.58；p < 0.001）。
通过BD先证者进行招募导致该样本中BD患病率增加，限制了研究结果的普遍性。无法获取的遗传数据减少了部分分析的样本量。
研究结果支持BD维度模型和分类模型之间的遗传连续性，并表明MDQ是BD遗传研究中一种有用的表型测量方法。
