Evidence for a possibly X-linked trait related to affective illness

The present report attempts to replicate on the probands' brothers, a previously reported (1992) negative relationship between maternal grandfather longevity (MGFL) and affective illness in grandsons. Hitherto this finding had not been replicated. To provide further evidence that the association may be recessive and X-linked, we also examined the association between MGFL and affective illness in the probands' mothers. Finally, in order to examine why MGFL might be a predictor of affective illness, the report examines the association of the probands' affective illness and their own mortality.

A 60-year prospective study of men selected in 1940 and followed until the present day provided good information on depressive illness in relatives and longevity of ancestors. To overcome the uncertainty of depressive diagnoses, we assessed affective illness in the probands categorically, dimensionally, operationally and with the Lazare Personality Inventory.

Presence of affective illness in brothers was negatively associated with MGFL (p = 0.003) but maternal affective illness was independent of MGFL. Test items suggesting emotional lability in the probands were significantly and negatively associated with MGFL. Consistent with the association of increased MGFL with low affective distress in the probands, the 70 probands showing the least evidence of affective distress before age 50 had twofold (p < 0.001) lower mortality at 80 than the rest of the sample. The 31 probands manifesting the greatest affective distress manifested twofold higher mortality before age 65 (p < 0.001) than the rest of the sample.

The strong negative association of proband affective distress -- and equally important -- the positive association of proband mental health with MGFL and the lack of association of maternal longevity and depression with MGFL points to the possibility of a recessive X-gene or genes playing a role in depressive illness.