A Family and Genetic Study of Primary Affective Disorders

T h e unitary concept of manic-depressive psychoses as originally proposed by Kraeplin (1921) has been questioned by recent investigators such as Leonhard (1965) and Perris (1966), who have presented clinical and genetic evidence to suggest that it is a heterogenous group consisting of two distinct types—(a) the unipolar which is characterised by recurrent episodes of depression only, and (b) the bipolar in which both manic and depressive episodes occur. Among the unipolar g roup , Woodruff et al. (1971) and Winokur et al. (1971, 1975) claim to have further distingushed two subtypes based on observed differences in family history between patients developing their first illness before the age of 40 yrs.—the depressive spectrum disease; and after the age of 40 yrs.—the pure depressive disease. Evidence for a genetic contribution to the etiology of pr imary affective disorders comes from both twin and family studies and has been summarised by Slater and Gowie (1971), and Gershon et al . (1975a). The work of Leonhard (1966), Angst (1966), and Perris (1966) have all provided data supporting the division into the unipolar and bipolar groups—each with its distinct genetic mechanism. Winokur and Tana (1969), on the basis of (a) the occurence of bipolar illness in successive generations, (b) a preponderance of female affected relatives of bipolar probands, and (c) the rarity of father to son transmission, have suggested the possibility of a single dominant gene located on the X chromosome in the bipolar group. However, other workers are not in agreement with this (Gershon e t a l . , 1975b and Smeraldi et al., 1977) although confirming the importance of genetic factors, suggest that bipolar and unipolar illness probably represent different thresholds on a continuous spectrum or scale of liability to affective disorders in which the bipolar form, because of its earlier age of onset and higher risk in relatives be considered a more severe form than unipolar illness. Winokur (1972) suggested the possibility of a second genetic factor—probably autosomal dominant —that may be more explicitly related to the expression of man i a rather than the X-linked factor which may generally predispose the individual to an Affective illness (either unipolar or b ipolar ) . Perris (1966) has also supported an Xlinked transmission, but only in the unipolar group. Zerbin-Rudin (1968) in a review of twin studies, showed tha t a high proportion of pairs of monozygotic twins, both of whom had an Affective illness, were such that one member suffered from a unipolar illness and the o ther from a bipolar illness; suggesting that they either have a common genetic basis, or that the individuals personality or environment in some way affects the outward expressivity of the bipolar genotype. Perris (1971) and Slater e t a l . (1971) using a computat ional model based on materna l and paternal incidence figures have reported da t a consistent with a polygenic pat tern of inheri tance for Affective illnesses. Finally, there is one report-Venkoba Rao (1974) who on the basis of a clinical study of 101 pat ients of