To the Editor.—
Berrettini et al,1 in the April 1990 issue of the Archives, claimed unequivocal rejection of linkage between X-chromosome markers and bipolar affective illness in a series of pedigrees collected at the National Institute of Mental Health, Bethesda, Md.1,2 Genetic linkage studies in psychiatric disorders are of great current interest. The report by Berrettini et al adds to a growing body of data on this topical subject. We have, however, reservations and concerns specific to the NIMH findings and comments on larger issues of linkage studies of affective disorders.1. Berrettini et al note that pedigrees with male-to-male transmission must be excluded in X-linkage analysis, and we agree. Although they claim to have done so, they included in the analysis a pedigree (0048) with clear evidence of male-tomale transmission. In that pedigree, subject 413 is a presumed carrier; his son, subject 415, has bipolar illness, and another son, subject