Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

96 E. Vieta et al.bipolar II probands were significantly more likely to have bipolar II relatives thanwere non-bipolar or bipolar I probands, but also that bipolar II probands wereslightly more likely than non-bipolar probands and slightly less likely than bipolar Iprobands to have relatives with bipolar I illness. A higher morbid risk of depressionamong relatives of bipolar II patients with regard to the group of unipolardepressive patients has been described (Kupfer et al., 1988). Gershon et al.(1982) noted that bipolar I and bipolar II disorders were more frequent in relativesof bipolar I and II patients than in relatives of unipolar depressives and controls.A study from Andreasen et al. (1987) showed higher familial loads of bipolar Idisorders in bipolar I subjects and an increase of bipolar II illness in the relatives ofbipolar II probands. In contrast with the results of Andreasen et al. (1987), Heunand Maier (1993) found that morbid risks for bipolar I disorder were equivalent inrelatives of bipolar I and bipolar II patients and lower in relatives of unipolarsubjects. However, the familial load for bipolar II disorder was higher in bipolar IIthan in bipolar I subjects, and lower in unipolar depressives and in controls.Bipolar II disorder has been reported to be the most prevalent affected phenotypein both bipolar I and bipolar II families and the only expressed phenotype in half ofthe bipolar II families (Simpson et al., 1993).With regard to genetics, a recent study from McMahon et al. (2001) found thatpaternal allele sharing on 18q21 was greatest in pairs where both siblings hadbipolar II–disorder. Prospective analysis confirmed the finding that bipolarII–bipolar II siblings pairs showed significantly greater paternal allele sharing.Paternal allele sharing across 18q21–23 was also significantly higher in familieswith at least one bipolar II–bipolar II sibling pair. In these families, multipointaffected sibling pair linkage analysis produced a peak paternal LOD score of 4.67versus 1.53 in all families. Therefore, affected sibling pairs with bipolar II discriminatedbetween families who showed evidence linkage to 18q and families whodid not. Families with a bipolar II sibling pair produced a increased lod score andimproved linkage resolution.NeuroimageKato et al.(1994) studied brain phosphorus metabolism in patients with bipolar Iand bipolar II disorder using magnetic resonance spectroscopy. Phosphocreatinelevels were lower in patients with bipolar II in the three states (euthymic, hypomanic,and depressed) compared to controls. High values of phosphomonoesterwere found in bipolar II patients in the hypomanic and depressive states, butphosphomonoester values in the euthymic state did not differ from controls.Intracellular pH of bipolar II patients in all phases was similar to control values,whereas euthymic bipolar I patients had lower pH values. The authors suggestedthat brain high-energy phosphate metabolism might be impaired in bipolar II