Maier W, Lichtermann D, Minges J, Hallmayer J, Heun R, Benkert O, Levinson D F
Department of Psychiatry, University of Mainz, Federal Republic of Germany.
Arch Gen Psychiatry. 1993 Nov;50(11):871-83. doi: 10.1001/archpsyc.1993.01820230041004.
It is widely acknowledged that the genetic diatheses for schizophrenia and affective disorders are independent. However, there are increasing doubts about this classic view, and empirical evidence for a dichotomy of these two prototypes of functional psychoses is limited. A controlled family study of consecutive admissions was conducted to determine whether familial risks for schizophrenic (SCZ) and affective disorders were independent or overlapping.
Index probands met Research Diagnostic Criteria for SCZ (n = 146), schizoaffective (SA [n = 115]), bipolar (BP [n = 80]), or unipolar major depressive (UP [n = 184]) disorder. Comparison probands met Research Diagnostic Criteria for alcoholism (n = 64) or were sampled from the general population (n = 109). A total of 2845 first-degree relatives were blindly diagnosed from interview, informant, and/or record data, with direct interviews completed in 2070 (82% of living first-degree relatives).
By Cox's proportional hazards analysis, SCZ, SA, BP, and UP disorders were familial, in that each group of relatives had an increased lifetime morbid risk (vs those with alcoholism and those from the general population) for the proband's diagnosis. The SCZ and BP disorders were transmitted independently: only probands with manic disorders (BP or SA-BP subtype) showed increased familial risks of BP disorder, and only probands with prominent SCZ features (SCZ or SA) showed increased familial risks of SCZ disorder. However, SCZ probands had an increased familial risk for UP disorder (as did SA, BP, and UP probands) and for the SA-UP subtype. Aggregation of depression in families of SCZ probands could not be explained by the subtype of depression, broad or narrow definition of SCZ disorder, presence or absence of history of depression in SCZ probands, whether onset of depression in a relative occurred before or after onset of a proband's SCZ disorder, or assortative mating.
These data suggest that there could be a familial relationship between the predispositions to schizophrenia and to major depression. We discuss a number of alternative hypotheses about the nature of this possible relationship.
人们普遍认为精神分裂症和情感障碍的遗传素质是相互独立的。然而，对于这一经典观点的质疑日益增多，且支持这两种功能性精神病原型二分法的实证证据有限。我们开展了一项针对连续入院患者的对照家庭研究，以确定精神分裂症（SCZ）和情感障碍的家族风险是相互独立还是重叠的。
索引先证者符合SCZ（n = 146）、分裂情感性（SA [n = 115]）、双相（BP [n = 80]）或单相重度抑郁（UP [n = 184]）障碍的研究诊断标准。对照先证者符合酒精中毒的研究诊断标准（n = 64）或从普通人群中抽样（n = 109）。通过访谈、 informant信息及/或记录数据对总共2845名一级亲属进行盲法诊断，对2070名（占在世一级亲属的82%）进行了直接访谈。
通过Cox比例风险分析，SCZ、SA、BP和UP障碍具有家族聚集性，即每组亲属患先证者所患疾病的终生发病风险均增加（与酒精中毒者及普通人群相比）。SCZ和BP障碍是独立遗传的：只有患有躁狂症的先证者（BP或SA - BP亚型）显示出BP障碍家族风险增加，只有具有明显SCZ特征的先证者（SCZ或SA）显示出SCZ障碍家族风险增加。然而，SCZ先证者患UP障碍的家族风险增加（SA、BP和UP先证者也是如此）以及患SA - UP亚型的风险增加。SCZ先证者家族中抑郁症的聚集现象无法通过抑郁症亚型、SCZ障碍的宽泛或狭义定义、SCZ先证者是否有抑郁症病史、亲属抑郁症发作是在先证者SCZ障碍发作之前还是之后，或选型交配来解释。
这些数据表明精神分裂症易感性和重度抑郁症易感性之间可能存在家族关系。我们讨论了关于这种可能关系本质的一些替代假说。
