Price R A, Kidd K K, Pauls D L, Gershon E S, Prusoff B A, Weissman M M, Goldin L R
J Psychiatr Res. 1985;19(4):533-46. doi: 10.1016/0022-3956(85)90071-8.
From the Yale-NIMH collaborative family study, the 1482 first degree relatives of 90 bipolar 1, and 163 major depression probands were examined to test the hypothesis that bipolar 1 and major depression are due to a single underlying genetic liability. We attempted to fit multifactorial-polygenic and single-major-locus multiple threshold models for sex and severity to the relatives in the major depression and bipolar 1 families. With relatives classified as affected only if they met criteria for major depression or bipolar 1, there was at best only marginal support for these models. Differences between these and previously reported results were examined in relation to differences in underlying assumptions. Additional analyses of these and other data from families of NIMH bipolar 2 and schizoaffective probands suggest that different methods of age adjustment, the relative placement of bipolar 2 and schizoaffective disorders in a hypothesized liability continuum and the inclusion or exclusion of sex thresholds were not primarily responsible for differences in the fit of genetic threshold models. Factors which do appear to be important are variability in rates between samples, the possibility of genetic heterogeneity, and the presence of a large secular increase in affective illness over the past three generations; the secular trend cannot be accommodated in the models of genetic transmission examined.
来自耶鲁大学与美国国立精神卫生研究所（NIMH）的合作家庭研究，对90名双相I型障碍患者和163名重度抑郁症先证者的1482名一级亲属进行了检查，以检验双相I型障碍和重度抑郁症是由单一潜在遗传易感性导致的这一假设。我们试图将性别和严重程度的多因素-多基因模型及单主基因座多阈值模型应用于重度抑郁症和双相I型障碍家庭中的亲属。仅当亲属符合重度抑郁症或双相I型障碍标准时才将其分类为患病，这些模型至多仅获得了微弱支持。针对这些结果与先前报告结果之间的差异，我们结合潜在假设的差异进行了考察。对来自NIMH双相II型障碍和分裂情感性障碍先证者家庭的这些数据及其他数据的进一步分析表明，不同的年龄调整方法、双相II型障碍和分裂情感性障碍在假设的易感性连续体中的相对位置以及性别阈值的纳入或排除，并非遗传阈值模型拟合差异的主要原因。似乎重要的因素包括样本间发病率的变异性、遗传异质性的可能性，以及在过去三代中情感性疾病出现的大幅长期增长；遗传传递模型无法解释这种长期趋势。
