Circadian disruption often demonstrates serial degradation: initially, the amplitude attenuates along with delayed circadian phase. With increasing acuity of illness, circadian rhythmicity may be lost entirely. Causes of chronodisruption may be environmental or internal to the patient. In particular, inadequate daytime illumination and nocturnal light pollution disrupt healthy circadian periodicity. Internal causes of circadian arrhythmia include critical illness itself and subjective experience of distress and pain. Observational studies of windowed rooms and real-time ambient lighting have found that physiologic light-dark patterns may support recovery from critical illness. Studies of early morning bright light or evening melatonin agonists have found improved rates of delirium, enhanced sleep, and lower arrhythmia prevalence. The current evidence base emphasizes that lighting and melatoninergic interventions deserve to be tested in full-scale trials.
Purpose Fatigue is one of the most disturbing complaints of cancer patients and often is the reason for discontinuing treatment. This randomized controlled study tested the hypothesis that increased morning bright light, compared to dim light, would result in less fatigue in women with breast cancer undergoing chemotherapy. Methods 39 women newly diagnosed with Stage I-III breast cancer were randomized to either bright white light (BWL) or dim red light (DRL) treatment and were instructed to use the light box for 30 minutes every morning throughout the first 4 cycles of chemotherapy. The Multidimensional Fatigue Symptom Inventory was administered prior to the start of chemotherapy (baseline), during the chemotherapy treatment week of cycle 1 (C1TW), the last week (recovery week) of cycle 1 (C1RW), chemotherapy treatment week of cycle 4 (C4TW), the last week (recovery week) of cycle 4 (C4RW). Results The DRL group reported increased fatigue at C1TW (p=0.003) and C4TW (p<0.001) compared to baseline while there was no significant change from baseline in the BWL group. A secondary analysis showed that the increases in fatigue levels in the DRL group were not mediated through associated with changes in sleep or in circadian rhythms as measured with wrist actigraphy. Conclusions The results of this study suggest that morning bright light treatment may prevent overall fatigue from worsening during chemotherapy. Although our hypothesis that overall fatigue would improve with bright light treatment was not supported, the lack of deterioration in total fatigue scores suggests that bright morning light may be a useful intervention during chemotherapy for breast cancer.
Genetic analysis in both mouse and Drosophila has indicated that the product of the CLOCK gene is an essential component of a circadian rhythm timing system. A single nucleotide polymorphism (SNP), T3111C, in the 3' flanking region of the human CLOCK gene has been identified. Homozygotes or heterozygotes for the 3111C allele have been reported to have higher mean scores on a measure of evening preference for activity (vs. morning preference) than subjects homozygous for the 3111T allele. Since major depression is hypothesized to be closely linked to circadian rhythms, we explored whether this polymorphism might be related to susceptibility to major depression. We also ascertained allele frequency in an African-American control population, to begin to evaluate population variation at this locus. CLOCK T3111C allele frequencies were determined in 280 European American (EA) subjects, 143 with a history of major depression and 137 screened controls, and in 58 African American (AA) screened control subjects, using a polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. There was no significant difference between EA depressed and control subjects in allele frequency. There was a significant difference in allele frequency between EA and AA subjects, demonstrating a potential for population stratification. In none of these groups were significant deviations from Hardy-Weinberg equilibrium found. The present data do not support an association between CLOCK gene alleles at the T3111C locus and major depression.
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