No abstract

Purpose While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Methods Women with ABC (n=97) and age-matched controls (n=24) took part in a 24-hour intensive physiological monitoring study involving polysomnographic sleep measures and high density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-hour and sleep-associated patterns of plasma cortisol, respectively. Results The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's>0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an 8-fold increase in the amount of objectively-measured wake time (p<0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r=−0.30, p=0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. Conclusions A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer.

Inflammation, the body’s response to harmful external agents, has long been found to be associated with depressive symptoms. The relationship between inflammation and depression is well established in the general population of people with depression, but is less so among perinatal women. Depression in the perinatal period is a common disorder, however available data do not indicate that there is a specific inflammatory picture associated with perinatal depression. We suggest that perinatal depression may be a heterogeneous construct, and that inflammation may be relevant to it in the context of other inflammatory morbidities of pregnancy. In this review we explore the available support for the hypothesis that inflammation associated with depression can represent a precipitating insult for the development of gestational diabetes, a known inflammatory morbidity of pregnancy.