For these analyses, the

18 subjects available were adequate. The availability of more observations would augment the precision of the estimates and enable independent cross-validation. Reductionistic and modular analysis of individual behavioral indicators may fail to capture trends that can become evident when multiple modules are considered simultaneously. This study compared the results from reductionistic and systemic multivariate or multidimensional approaches to understand the changes in behavioral indicators associated with infection status. Four sickness indicators and three depression-like indicators were measured in mice receiving either one of three BCG-treatment levels. Mice treated with BCG exhibited sickness as indicated by changes in body weight during the first days after the challenge. Although the difference in sickness indicators learn more between BCG-treatment groups subsided by Day 5, differences in depression-like indicators

were detected in subsequent days. The previous trends were weaker or less recognizable in the univariate reductionist analysis than in the multivariate systemic analysis. Our results showed that the classical univariate analysis of indicators individually may fail to capture borderline trends. This finding is important because detecting subtle differences between treatment groups or subjects within treatment group is becoming more critical with the recognition of the effectiveness of individualized Cetuximab research buy therapies. Furthermore, the multivariate and multidimensional approaches offered information on the relationship between behavioral indicators and between mice within and across treatment groups, in addition to traditional test statistics. Cluster, multidimensional reduction and scaling analyses further characterized the interplay between sickness and depression-like indicators. The distribution of mice across sickness and depression-like dimensions confirmed that the BCG5 treatment elicited weaker changes in sickness and depression-like indicators than

the BCG10 treatment. Also, the distribution of mice within BCG-treatment group confirmed mouse-to-mouse variation on the susceptibility to challenge across the multiple behavior indicators. This result suggests that studies aimed at characterizing Erastin supplier mouse-to-mouse variation may consider low BCG dose levels. Subject-to-subject variation in behavioral response to infection and identification of differential susceptibility has been reported in humans (Walker et al., 2011). Beyond the polygenic nature of susceptibility to BCG challenge, results from the multivariate analysis suggested an epistatic mode of action of some genes across indicators. The impact of indoleamine 2,3-dioxygenase on the development of BCG-induced behavioral changes has been demonstrated (O’Connor et al., 2009).