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Results of a Controlled Family Study

Wolfgang Maier, MD; Dirk Lichtermann, MD; Jurgen Minges, MD; Joachim Hallmayer, MD; Reinhard Heun, MD; Otto Benkert, MD; F. Levinson Douglas, MD

Arch Gen Psychiatry. 1993;50(11):871-883.

Abstract
Background
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.

Methods
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).

Results
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.

Conclusions
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.

Footnotes
From the Department of Psychiatry, University of Mainz (Federal Republic of Germany) (Drs Maier, Lichtermann, Minges, Hallmayer, Heun, and Benkert), and the Department of Psychiatry, Medical College of Pennsylvania, Philadelphia (Dr Levinson).

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