Serotonin transporter polymorphism, depressive symptoms, and emotional impulsivity among advanced breast cancer patients

This study tested a theory linking a marker of low serotonergic function to both depression and impulsivity in a sample of advanced breast cancer patients, among whom elevated depressive symptoms and difficulty regulating emotions are commonly reported.A total of 95 patients provided blood samples for serotonin transporter polymorphic region of the gene (5-HTTLPR) and completed questionnaires that measured depressive symptoms and emotional impulsivity.Structural equation modeling revealed that the s allele of 5-HTTLPR was related to greater depressive symptoms (β = .20, p < .042) but only marginally to greater emotional impulsivity (β = .19, p < .068). Depressive symptoms and emotional impulsivity were positively related (β = .33, p < .003). Further tests explored possible mediation from genotype to one psychological variable via the other. Results suggest that depressive symptoms, particularly perceived interpersonal rejection, may be a pathway linking genotype to emotional impulsivity.Findings provide the first evidence that low serotonergic function contributes to both depression and impulsivity within a clinically meaningful sample. Furthermore, the link of s allele of 5-HTTLPR to emotional impulsivity was mediated by depressive symptoms, particularly perceptions of social rejection. Findings have implications for advanced breast cancer patients’ treatment decision

Lower peak numbers, blunted diurnal rhythms of immune cell distribution, and sleep disruption in metastatic breast cancer

Rationale : The peak number of protective immune cells measured in the blood at the zenith of their diurnal rhythm is a measure of their overall capacity for immunoprotection. Rhythmic diurnal changes in blood immune cell numbers reflect a redistribution of cells from the blood to other body compartments, and back into the blood. This redistribution may be critical for leukocyte maintenance and for the surveillance and effector functions of the immune system. Methods : We investigated diurnal changes in absolute numbers of NK cells in patients with metastatic breast cancer (MBC) (n=48) and controls (n=19). Sleep quality was measured by home actigraphy. Leukocyte differentials were combined with flow cytometry to calculate NK cell numbers in whole blood samples obtained every 4h, starting 12 h (T1) after the midpoint of sleep on day 1 and ending 12 h (T7) after the midpoint of sleep on day 2. Results : In agreement with the literature, control subjects showed peak blood NK cell numbers at T1, with a decrease to their diurnal trough at around the sleep midpoint (T4), followed by a return to diurnal peak numbers 12 h later. Compared to controls, patients with MBC showed significantly lower peak NK cell numbers (p=0.039), suggesting an overall decrease in NK-cell-mediated immunoprotection for patients. Interestingly, among patients, higher peak NK cell numbers were associated with a longer disease-free interval (p=0.036) and higher Karnofsky Performance Rating (p=0.083, trend), collectively indicating an association between higher peak NK cell numbers and better health and functional status. Compared to controls, patients with MBC also showed a smaller peak to trough decrease (p=0.006) that suggests reduced diurnal NK cell redistribution among different immune compartments which could also decrease immunoprotection. We further investigated the relationship between sleep disruption and damped NK cell rhythms in MBC patients. Higher average wake time after sleep onset was associated with a smaller peak to trough decrease (R=&#x200A;&#x2212;&#x200A;0.38, p=0.006). The average number of awakenings was also associated with a smaller peak to trough decrease (R=&#x200A;&#x2212;&#x200A;0.36, p=0.014). In contrast, average sleep efficiency was associated with a larger peak to trough decrease (R=&#x200A;&#x2212;&#x200A;0.40, p=0.005), indicating a positive association between better sleep and a healthier diurnal NK cell rhythm. Conclusion : These results suggest that patients with MBC have reduced NK-cell-mediated immunoprotection compared to controls and that among patients, higher NK cell numbers are related to longer disease-free interval and better Karnofsky status. Patients with MBC also show decreased diurnal NK cell redistribution compared to controls, and among patients, reduced diurnal NK cell redistribution is associated with increased sleep disruption

Sleep Disturbances in Women With Metastatic Breast Cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73246/1/j.1524-4741.2002.08606.x.pd

Loneliness within a nomological net: An evolutionary perspective

Abstract Loneliness is characterized by feelings of social pain and isolation and has both heritable and unshared environmental underpinnings. An evolutionary theory of loneliness is outlined, and four studies replicate and extend prior research on the characteristics of lonely individuals. Studies 1 and 2 indicate that loneliness and depressed aVect are related but separable constructs. Study 3 conWrms that lonely, relative to nonlonely, young adults are higher in anxiety, anger, negative mood, and fear of negative evaluation, and lower in optimism, social skills, social support, positive mood, surgency, emotional stability, conscientiousness, agreeableness, shyness, and sociability. The set of six personality factors associated with loneliness (surgency, emotional stability, agreeableness, conscientiousness, shyness, and sociability) do not explain the associations between loneliness and negative mood, anxiety, anger, optimism (pessimism), self-esteem, and social support, as each association remained statistically signiWcant even after statistically controlling for these personality factors. Study 4 used hypnosis to experimentally manipulate loneliness to determine whether there were associated J.T. Cacioppo et al. / Journal of Research in Personality 40 (2006) 1054-1085 1055 changes in the participants&apos; personality and socioemotional characteristics. Results conWrmed that loneliness can inXuence the participants&apos; personality ratings and socioemotional states

Lower peak numbers, blunted diurnal rhythms of immune cell distribution, and sleep disruption in metastatic breast cancer

Rationale : The peak number of protective immune cells measured in the blood at the zenith of their diurnal rhythm is a measure of their overall capacity for immunoprotection. Rhythmic diurnal changes in blood immune cell numbers reflect a redistribution of cells from the blood to other body compartments, and back into the blood. This redistribution may be critical for leukocyte maintenance and for the surveillance and effector functions of the immune system. Methods : We investigated diurnal changes in absolute numbers of NK cells in patients with metastatic breast cancer (MBC) (n=48) and controls (n=19). Sleep quality was measured by home actigraphy. Leukocyte differentials were combined with flow cytometry to calculate NK cell numbers in whole blood samples obtained every 4h, starting 12 h (T1) after the midpoint of sleep on day 1 and ending 12 h (T7) after the midpoint of sleep on day 2. Results : In agreement with the literature, control subjects showed peak blood NK cell numbers at T1, with a decrease to their diurnal trough at around the sleep midpoint (T4), followed by a return to diurnal peak numbers 12 h later. Compared to controls, patients with MBC showed significantly lower peak NK cell numbers (p=0.039), suggesting an overall decrease in NK-cell-mediated immunoprotection for patients. Interestingly, among patients, higher peak NK cell numbers were associated with a longer disease-free interval (p=0.036) and higher Karnofsky Performance Rating (p=0.083, trend), collectively indicating an association between higher peak NK cell numbers and better health and functional status. Compared to controls, patients with MBC also showed a smaller peak to trough decrease (p=0.006) that suggests reduced diurnal NK cell redistribution among different immune compartments which could also decrease immunoprotection. We further investigated the relationship between sleep disruption and damped NK cell rhythms in MBC patients. Higher average wake time after sleep onset was associated with a smaller peak to trough decrease (R=&#x200A;&#x2212;&#x200A;0.38, p=0.006). The average number of awakenings was also associated with a smaller peak to trough decrease (R=&#x200A;&#x2212;&#x200A;0.36, p=0.014). In contrast, average sleep efficiency was associated with a larger peak to trough decrease (R=&#x200A;&#x2212;&#x200A;0.40, p=0.005), indicating a positive association between better sleep and a healthier diurnal NK cell rhythm. Conclusion : These results suggest that patients with MBC have reduced NK-cell-mediated immunoprotection compared to controls and that among patients, higher NK cell numbers are related to longer disease-free interval and better Karnofsky status. Patients with MBC also show decreased diurnal NK cell redistribution compared to controls, and among patients, reduced diurnal NK cell redistribution is associated with increased sleep disruption

Bedtime misalignment and progression of breast cancer

Disruption of circadian rhythms, which frequently occurs during night shift work, may be associated with cancer progression. The effect of chronotype (preference for behaviors such as sleep, work, or exercise to occur at particular times of day, with an associated difference in circadian physiology) and alignment of bedtime (preferred vs. habitual), however, have not yet been studied in the context of cancer progression in women with breast cancer. Chronotype and alignment of actual bedtime with preferred chronotype were examined using the Morningness–Eveningness Scale (MEQ) and sleep-wake log among 85 women with metastatic breast cancer. Their association with disease-free interval (DFI) was retrospectively examined using the Cox proportional hazards model. Median DFI was 81.9 months for women with aligned bedtimes (“going to bed at preferred bedtime”) (n=72), and 46.9 months for women with misaligned bedtimes (“going to bed later or earlier than the preferred bedtime”) (n=13) (log rank p=0.001). In a multivariate Cox proportional hazard model, after controlling for other significant predictors of DFI, including chronotype (morning type/longer DFI; HR=0.539, 95% CI=0.320–0.906, p=0.021), estrogen receptor (ER) status at initial diagnosis (negative/shorter DFI; HR=2.169, 95% CI=1.124–4.187, p=0.028) and level of natural-killer cell count (lower levels/shorter DFI; HR=1.641, 95% CI=1.000–2.695, p=0.050), misaligned bedtimes was associated with shorter DFI, compared to aligned bedtimes (HR=3.180, 95% CI=1.327–7.616, p=0.018). Our data indicate that a misalignment of bedtime on a daily basis, an indication of circadian disruption, is associated with more rapid breast cancer progression as measured by DFI. Considering the limitations of small sample size and study design, a prospective study with a larger sample is necessary to explore their causal relationship and underlying mechanisms

Aberrant nocturnal cortisol and disease progression in women with breast cancer

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