97 Furthermore, in

shift workers, dyschronism disappears (both the symptoms and the desynchronization) when the subject returns to regular lifestyle, and medications are ineffective in the treatment of intolerance to shift work. We can thus conclude that there is a strong link between changes in rhythm τ values and clinical symptoms in dyschronism, whereas such a link is not present or else very weak in depressive states and can be evidenced in only a fraction of cases. Consequently, depression and dyschronism presumably represent two different nosological entities. Putative mechanisms involved in allochronism and dyschronism In a discussion on depression, Kripke95, 98 raised the idea that it is the individual sensitivity Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical to desynchronization, rather than the desynchronization itself, that tips the scale between the occurrence and nonoccurrence

of clinical symptoms. This idea can be extended to interindividual differences in the occurrence of symptoms resulting from intolerance to jet lag, shift work, and disease-related chronic deprivation of night sleep. Temporal organization variability has been known for many years. Its association with clinical and pathological conditions has also been documented. However, there has been no attempt to array the temporal organization variants and, consequently, no experimental Inhibitors,research,lifescience,medical data are available with regard to the mechanisms that underlie this Inhibitors,research,lifescience,medical variability. We will offer here some hypotheses and models for possible putative mechanisms involved in allochronism (temporal organization variants without clinical symptoms) and dyschronism (temporal organization variants with clinical symptoms). Hypothesis A rather large variety of environmental factors Inhibitors,research,lifescience,medical serve as signals that may affect the

human temporal organization. Let us assume that two groups, A and B, are exposed to any of these signals. In group A, no changes in the time structure are detected (nonreactors) , while in group B, changes are detected (reactors). Group B can then divided to two subgroups: group Bl , in whom no clinical symptoms or complaints are encountered; and group B2, in whom clinical symptoms and complaints are found. According to our terminology, group B1 should be categorized as having allochronism and group B2 dyschronism. The presence of interindividual variability (with genderrelated differences) and variability in the propensity of human subjects to Mephenoxalone exhibit a change (even NVP-AUY922 supplier temporary, ie, reversible),48, 64 suggests the involvement of genetic factors. However, while the mere presence of variability can be explained by simple models of genetic polymorphism, more complicated control mechanisms are needed to explain why some people are more prone to change their temporal organization than others, even if natural zeitgebers are present, and suggest how these changes can be reversed.