Other temperaments also indicated several regions of interest that were not GW significant, such as the common finding of association (p<10−4) to the LRRC4C gene region for the hyperthymic, dysthymic, and cyclothymic temperaments, with the hyperthymic temperament giving an effect in the opposite direction. These three temperaments have been shown to predict risk for bipolar spectrum disorders, with the hyperthymic temperament being of specific relevance to BDI. This may explain the superior performance of this temperament in our sample of BDI subjects. The dysthymic temperament is characterized by low energy, low spirits, and negative cognitions and may thus be more relevant to major depressive disorder than BDI. The cyclothymic temperament is characterized by rapid and unpredictable mood swings between the depressive and the hyperthymic poles and has been conceptualized as a subthreshold expression of bipolarity that may be of particular relevance to the BDII subtype based on clinical and prospective data showing high sensitivity and specificity of cyclothymic lability for BDII (9,43). Interestingly, one study reported high heritability estimates for the hyperthymic (50.9%, p<0.001) and irritable (74.8%, p<0.001) temperaments in
