Publications

BACKGROUND: Major cancer organizations recommend depression screening in patients and survivors. The 9-item Patient Health Questionnaire (PHQ-9) is often suggested, with limited information about its use.

METHODS: Enrollment data collected from younger breast cancer survivors participating in a behavioral intervention trial were used to examine the relationship between PHQ-9 scores (range = 0-27), patient characteristics, and responses to standardized psychosocial assessment tools. Major depressive disorder criterion was met if responses to the first 2 PHQ-9 items (range = 0-6) were 3 or greater. The sample was categorized by total PHQ-9 scores: less than 5 (minimal depressive symptoms), 5-9 (mild to moderate depressive symptoms), and 10 or greater (moderate to severe depression). PHQ-9 category associations with medical, demographic, psychosocial, and behavioral characteristics were examined using analysis of variance for continuous variables and χ2 tests for categorical variables.

RESULTS: A total of 231 women met the study prescreening eligibility criterion of mild depressive symptoms and enrolled in the study. On average, they were 45.2 years old and 2.6 years since diagnosis. At enrollment, 22.1% met the screening criterion for possible major depressive disorder; among those with PHQ-9 scores of 10 or greater, 58.3% met this criterion. Anxiety, fatigue, insomnia, and intrusive thoughts about cancer were frequent and were associated with depressive symptom severity (all P < .001). In contrast, neither demographic nor cancer treatment characteristics were associated with depressive symptoms.

CONCLUSIONS: Depressive symptoms in this selected sample of younger breast cancer survivors were independent of demographic characteristics or cancer treatment history, suggesting that depression screening is necessary to detect uncontrolled depressive symptoms.

Sleep disturbances and insomnia are common among breast cancer survivors, and can have a significant effect on quality of life and numerous other significant outcomes. Among risks for sleep disturbance is the introduction of anti-estrogen endocrine therapies. The possible contributing factors to sleep disturbance in endocrine therapy are complex, and include pre-existing sleep disorders, the effects of chemotherapy and other treatments, and concurrent symptoms such as hot flashes. In addition, sleep disturbance in menopause, the natural downregulation of reproductive hormones in older age, is a common occurrence, and can offer a model for understanding the high prevalence of sleep problems in breast cancer survivors on endocrine therapy, as well as suggesting possible treatments such as behavioral interventions and pharmaceuticals. Altogether, significantly more research is needed to better understand and address sleep disturbance in breast cancer survivors on endocrine therapy in order to support quality of life and treatment adherence.

Women remain underrepresented within academic medicine despite past and present efforts to promote gender equity. The authors discuss how the COVID-19 pandemic could stymie progress toward gender parity within the biomedical workforce and limit the retention and advancement of women in science and medicine. Women faculty face distinct challenges as they navigate the impact of shelter-in-place and social distancing on work and home life. An unequal division of household labor and family care between men and women means women faculty are vulnerable to inequities that may develop in the workplace as they strive to maintain academic productivity and professional development without adequate assistance with domestic tasks and family care. Emerging data suggest that gender differences in academic productivity may be forthcoming as a direct result of the pandemic. Existing gender inequities in professional visibility, networking, and collaboration may be exacerbated as activities transition from in-person to virtual environments and create new barriers to advancement. Meanwhile, initiatives designed to promote gender equity within academic medicine may lose key funding due to the economic impact of COVID-19 on higher education. To ensure that the gender gap within academic medicine does not widen, the authors call upon academic leaders and the broader biomedical community to support women faculty through deliberate actions that promote gender equity, diversity, and inclusion. The authors provide several recommendations, including faculty needs assessments; review of gender bias within tenure-clock-extension offers; more opportunities for mentorship, sponsorship, and professional recognition; and financial commitments to support equity initiatives. Leadership for these efforts should be at the institutional and departmental levels, and leaders should ensure a gender balance on task forces and committees to avoid overburdening women faculty with additional service work. Together, these strategies will contribute to the development of a more equitable workforce capable of transformative medical discovery and care.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep-wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

Intermittent light (IML) pulses are more efficient per minute of exposure than continuous exposure in resetting the phase of the human circadian pacemaker. We assessed the spectral sensitivity in phase resetting, melatonin suppression and alertness induced by IML pulses. Twelve healthy young adults (6 females; mean age ± SD = 25.4 ± 3.6 years) were exposed to six monochromatic light pulses (2.8 × 1013 photons/cm2/s) over a 6.5 h window during the biological night. Six participants (3F) received 6 × 15-minute 460 nm (blue) pulses and six participants received 6 × 2-minute 555 nm (green) light pulses. Results were compared to historical data in 16 individuals who received continuous 460 nm (n = 8) or 555 nm (n = 8) light exposure using an identical protocol. As expected, long duration continuous 460 nm light exposure induced the largest total phase delay shifts, but intermittent 555 nm light induced the largest phase delay shifts per minute of the photic stimulus. Melatonin suppression was significantly higher under continuous light exposure compared to intermittent exposure patterns, and for 460 nm versus 555 nm exposure (under both light patterns). These data extend prior work showing a non-linear relationship between light exposure duration and phase resetting responses and illustrate the potential role of light wavelength, and therefore photoreceptor recruitment, in mediating these responses.

PURPOSE: Younger women are at risk for depression and related symptoms following breast cancer. The Pathways to Wellness study, a randomized, multi-institution, three-arm trial, tested the efficacy of two behavioral interventions for younger breast cancer survivors with elevated depressive symptoms: mindful awareness practices (MAPs) and survivorship education (SE) (Clincaltrials.gov identifier: NCT03025139).

METHODS: Women diagnosed with breast cancer at or before 50 years of age who had completed treatment and had elevated depressive symptoms were randomly assigned to 6 weeks of MAPs, SE, or wait-list control (WLC). Assessments were conducted preintervention and postintervention and at 3-month and 6-month postintervention follow-ups. Analyses compared each intervention to WLC using linear mixed models. The primary outcome was change in depressive symptoms from preintervention to postintervention on the Center for Epidemiologic Studies-Depression Scale; secondary outcomes included change in fatigue, insomnia, and vasomotor symptoms.

RESULTS: Two hundred forty-seven women (median age = 46 years) were randomly assigned to MAPs (n = 85), SE (n = 81), or WLC (n = 81). MAPs and SE led to significant decreases in depressive symptoms from preintervention to postintervention relative to WLC (mean change relative to WLC [95% CI]: MAPs, -4.7 [-7.5 to -1.9]; SE, -4.0 [-6.9 to -1.1]), which persisted at 6-month follow-up for MAPs (mean change relative to WLC [95% CI]: MAPs, -3.7 [-6.6 to -0.8]; SE, -2.8 [-5.9 to 0.2]). MAPs, but not SE, also had beneficial effects on fatigue, insomnia, and vasomotor symptoms that persisted at 6-month follow-up (P < .05).

CONCLUSION: Mindfulness meditation and SE reduced depressive symptoms in younger breast cancer survivors. These interventions can be widely disseminated over virtual platforms and have significant potential benefit for quality of life and overall survivorship in this vulnerable group.

STUDY OBJECTIVES: To evaluate how change in menopausal status related to spectral analysis and polysomnographic measures of sleep characteristics.

METHODS: The Study of Women's Health Across the Nation (SWAN) Ancillary Sleep Study evaluated sleep characteristics of 159 women who were initially pre- or early perimenopausal and repeated the assessment about 3½ years later when 38 were pre- or early perimenopausal, 31 late perimenopausal, and 90 postmenopausal. Participants underwent in-home ambulatory polysomnography for two to three nights. Average EEG power in the delta and beta frequency bands was calculated during NREM and REM sleep, and sleep duration, wake after sleep onset (WASO), and apnea hypopnea index (AHI) were based on visually-scored sleep.

RESULTS: The women who transitioned to postmenopause had increased beta NREM EEG power at the second assessment, compared to women who remained pre-or early premenopausal; no other sleep measures varied by change in menopausal status. In multivariate models the associations remained; statistical controls for self-reported hot flashes did not explain findings. In secondary analysis, NREM beta power at the second assessment was greater among women who transitioned into the postmenopause after adjustments for initial NREM beta power.

CONCLUSIONS: Sleep duration and WASO did not vary by menopause transition group across assessments. Consistent with prior cross-sectional analysis, elevated beta EEG power in NREM sleep was apparent among women who transitioned to postmenopause, suggesting that independent of self-reported hot flashes, the menopausal transition is associated with physiological hyperarousal during sleep.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7 hours and -4.2 hours, respectively, compared to -6.6 hours and -4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

CONTEXT: Women are at increased risk for depressive symptoms during the menopause transition. Changes in estradiol secretion and presence of vasomotor symptoms (VMS) contribute to perimenopausal depressive symptoms, but links with progesterone have not been investigated.

OBJECTIVE: To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology.

DESIGN AND INTERVENTION: Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models.

SETTING: Academic medical center.

PATIENTS: Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 15.5 ± 5.3).

MAIN OUTCOME MEASURE: Depressive symptoms (MADRS score).

RESULTS: During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (β = 0.11 [95% confidence interval (95% CI), 0.04 to 0.18; P = 0.001]; β = -2.62 [95% CI, -4.52 to -0.71; P = 0.007], respectively), after accounting for higher body mass index, lifetime history of depression, and stressful life events.

CONCLUSIONS: Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.