Dysfunction of the circadian clocks plays

Dysfunction of the circadian clocks plays a role in mood disorders (). It is not known, however, whether they have a causal role in the etiology or display their effects on mood later during the pathogenesis. Basic research findings from mice recently pointed out that circadian rhythm abnormalities directly correlated with depression-like behavior following unpredictable chronic mild stress in wild-type mice (), and that the genetic disruption of Exendin-3 (9-39) amide by specific deletion of a key clock gene in the suprachiasmatic nucleus did cause helplessness, behavioral despair and anxiety-like behavior (). Now, new pieces have been added to this puzzling picture. Recently in , reported a clinical study and suggested that abnormalities in the circadian clocks might be a key pathophysiological mechanism of bipolar disorder. They repeatedly measured biochemical circadian rhythms in patients with bipolar disorder during hospitalization from ill states at admission to euthymic states at discharge, and compared them with those of healthy controls. Moon and colleagues found that the circadian rhythms had abnormal phases during acute mood episodes, and that these returned to normal after treatment. The way back to normal mood, however, took diverse routes, since the recovery of depressive episodes was through phase advances of 4 to 5h and that of mixed episodes, which present depressive and manic states together, through phase advances of 6 to 7h. In contrast, concerning manic episodes, the abnormal phases resolved on average through delays by 7h or advances by 17h to recover the normal rhythm after treatment. Current clinical practice should next pay more attention to the assessment of the timing and regularity of bedtimes and wake-up calls, rather than just sleep duration and sleep quality. It appears that even after taking sleep disturbances into account, current depressive episodes tend to demonstrate a link to the timing of daily activities guided by the circadian clocks (). Therefore, abnormalities in the circadian clocks deserve clinical attention. Significance of the report of Moon and colleagues to basic scientists lies in the possibility to develop of the assessment of circadian rhythms a biomarker for diagnosis and treatment monitoring in bipolar disorder. In this effort, the molecular characterization of the individual’s schedule for the timing of daily activities is the first step. These schedules form a continuum, or chronotype, with the anchorage poles of “early birds” and “night owls”. Some preliminary attempts to reach this goal have been made (). This being said, there are naturally many unanswered questions that still need addressing. Questions such as, whether the findings of Moon and colleagues hold in mood disorders at large, or in other words, can they be replicated also in depressive disorders, await. On the other hand, a clinically hot question will be which one, if any, of the trajectories for recovery does hold in those mood disorders that follow a seasonal pattern (), since these patients are most likely to benefit from treatment options that influence the circadian clocks. All these need to be addressed with prospective trials.
Telomeres, tandem TTAGGG nucleotide repeats located at the ends of eukaryotic chromosomes, are DNA-protein complexes critical to the maintenance of genomic stability and cellular longevity. They are among the most-studied markers of the aging process, with multiple studies showing that telomeres shorten with age. This, in turn, has led researchers to posit a relationship between telomere shortening and a variety of age-related health conditions, particularly cancer. Many studies have identified associations between cancer risk and both longer and shorter telomeres (), a contradiction that can potentially be explained via a dynamic relationship over time wherein people early in cancer development experience accelerated telomere shortening that is subsequently arrested as cancer cells hijack various telomere lengthening mechanisms (). This process is believed to be necessary not only for immortalizing cells, but also because it can be used to delay cell senescence and thus provide opportunity for the accumulation of additional mutations (via DNA damage or other processes) necessary to complete the transformation into a cancerous cell ().