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Am J Psychiatry 1992; 149:1660-1665
Copyright © 1992 by American Psychiatric Association
Assessment of lineality in bipolar I linkage studies
SG Simpson, SE Folstein, DA Meyers and JR DePaulo
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD.
OBJECTIVE: To assess lineality in families of bipolar I probands, the
authors used direct interviews of family members to reclassify families
initially categorized as unilineal by family history. METHOD: The families
of 1,800 treated bipolar I probands were screened by the family history
method with multiple informants. If the proband had one or more affected
sibs and one apparently unaffected parent, the parents (and then other
available first- and second-degree relatives) were directly interviewed by
psychiatrists. RESULTS: Of the 1,800 families screened, 56 were apparently
suitable unilineal families with multiple affected members; 46 families
were interviewed directly. After interviews with the parents, 12 families
(26.1%) were found to be bilineal. Direct interviews of all available
relatives in the 34 remaining families revealed that only 22 (47.8% of the
46 interviewed families) were unilineal or probably unilineal and 12 were
probably bilineal. The probably bilineal families had a significantly
higher proportion of siblings with unipolar disorder. In addition, the
affected sibs from the probably bilineal families tended to have earlier
onsets but had significantly fewer symptoms in the most severe depressive
episode. CONCLUSIONS: Fewer than 50% of bipolar I families appearing
unilineal according to family history were found to be unilineal by direct
interviews. The phenotypic differences between the affected sibs from the
probably bilineal families and those from the unilineal and probably
unilineal families suggest differences in genetic mechanisms. These
findings highlight the need to systematically assess lineality in all
families considered for bipolar I linkage studies and support the
preferential inclusion of unilineal families in linkage studies.
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