Publications by authors named "Aric A Prather"

85 Publications

"GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder.

Transl Psychiatry 2021 Apr 6;11(1):193. Epub 2021 Apr 6.

Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.

Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer's disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Among such metrics, estimators of biological age based on predictable age-related patterns of DNA methylation (DNAm), so-called 'epigenetic clocks', have shown particular promise for their ability to capture accelerated aging in psychiatric disease. The recently developed DNAm metric known as 'GrimAge' is unique in that it was trained on time-to-death data and has outperformed its predecessors in predicting both morbidity and mortality. Yet, GrimAge has not been investigated in MDD. Here we measured GrimAge in 49 somatically healthy unmedicated individuals with MDD and 60 age-matched healthy controls. We found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age ('AgeAccelGrim') compared to healthy controls (p = 0.001), with a median of 2 years of excess cellular aging. This difference remained significant after controlling for sex, current smoking status, and body-mass index (p = 0.015). These findings are consistent with prior suggestions of accelerated cellular aging in MDD, but are the first to demonstrate this with an epigenetic metric predictive of premature mortality.
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http://dx.doi.org/10.1038/s41398-021-01302-0DOI Listing
April 2021

The long shadow of childhood trauma for depression in midlife: examining daily psychological stress processes as a persistent risk pathway.

Psychol Med 2021 Mar 26:1-10. Epub 2021 Mar 26.

Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.

Background: Childhood trauma (CT) increases the risk of adult depression. Buffering effects require an understanding of the underlying persistent risk pathways. This study examined whether daily psychological stress processes - how an individual interprets and affectively responds to minor everyday events - mediate the effect of CT on adult depressive symptoms.

Methods: Middle-aged women (N = 183) reported CT at baseline and completed daily diaries of threat appraisals and negative evening affect for 7 days at baseline, 9, and 18 months. Depressive symptoms were measured across the 1.5-year period. Mediation was examined using multilevel structural equation modeling.

Results: Reported CT predicted greater depressive symptoms over the 1.5-year time period (estimate = 0.27, s.e. = 0.07, 95% CI 0.15-0.38, p < 0.001). Daily threat appraisals and negative affect mediated the effect of reported CT on depressive symptoms (estimate = 0.34, s.e. = 0.08, 95% CI 0.22-0.46, p < 0.001). Daily threat appraisals explained more than half of this effect (estimate = 0.19, s.e. = 0.07, 95% CI 0.08-0.30, p = 0.004). Post hoc analyses in individuals who reported at least moderate severity of CT showed that lower threat appraisals buffered depressive symptoms. A similar pattern was found in individuals who reported no/low severity of CT.

Conclusions: A reported history of CT acts as a latent vulnerability, exaggerating threat appraisals of everyday events, which trigger greater negative evening affect - processes that have important mental health consequences and may provide malleable intervention targets.
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http://dx.doi.org/10.1017/S0033291721000921DOI Listing
March 2021

A reply to Shachak.

J Am Med Inform Assoc 2021 Feb 28. Epub 2021 Feb 28.

Center for Health and Community, University of California, San Francisco, California, USA.

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http://dx.doi.org/10.1093/jamia/ocab022DOI Listing
February 2021

Early life adversity, pubertal timing, and epigenetic age acceleration in adulthood.

Dev Psychobiol 2021 Jan 10. Epub 2021 Jan 10.

University of California, San Francisco, CA, USA.

Background: Given associations linking early life adversity, pubertal timing, and biological aging, we examined the direct and indirect effects of early life trauma on adult biological aging (via age of menarche).

Methods: Participants were premenopausal women (N = 183). Path models evaluated whether early life trauma predicted early pubertal timing and thereby, adult epigenetic age acceleration (indexed via four epigenetic clocks: Horvath DNAm Age, Hannum DNAm Age, DNAm PhenoAge, and DNAm GrimAge). Secondary analyses explored the effects of type of trauma (abuse and neglect) and adult chronic stress status (caregiver of child with autism and non-caregiver).

Results: Early life trauma and earlier age at menarche independently predicted accelerated aging based on one of the four epigenetic clocks, DNAm GrimAge, though early life trauma was not associated with age of menarche. Childhood abuse, but not neglect, predicted faster epigenetic aging; results did not differ by chronic stress status.

Conclusions: Early trauma and early menarche appear to exert independent effects on DNAm GrimAge, which has been shown to be the strongest epigenetic predictor of mortality risk. This study identifies a potential correlate or determinant of accelerated epigenetic aging-menarcheal age. Future research should address the limitations of this study by using racially diverse samples.
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http://dx.doi.org/10.1002/dev.22085DOI Listing
January 2021

HPA axis regulation and epigenetic programming of immune-related genes in chronically stressed and non-stressed mid-life women.

Brain Behav Immun 2021 Feb 19;92:49-56. Epub 2020 Nov 19.

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Carolina Stress Initiative, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address:

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been associated with altered immune function, but the underlying molecular mechanisms are unclear. Epigenetic processes, including DNA methylation, respond to the glucocorticoid end-products of the HPA axis (cortisol in humans) and could be involved in this neuroendocrine-immune crosstalk. Here we examined the extent to which variations in HPA axis regulation are associated with peripheral blood DNA (CpG) methylation changes in 57 chronically stressed caregivers and 67 control women. DNA methylation was determined with the Illumina 450k array for a panel of genes involved in HPA axis and immune function. HPA axis feedback was assessed with the low-dose dexamethasone suppression test (DST), measuring the extent to which cortisol secretion is suppressed by the synthetic glucocorticoid dexamethasone. After multiple testing correction in the entire cohort, higher post-DST cortisol, reflecting blunted HPA axis negative feedback, but not baseline waking cortisol, was associated with lower DNA methylation at eight TNF and two FKBP5 CpG sites. Caregiver group status was associated with lower methylation at two IL6 CpG sites. Since associations were most robust with TNF methylation (32% of the 450k-covered sites), we further examined functionality of this epigenetic signature in cultured peripheral blood mononuclear cells in 33 participants; intriguingly, lower TNF methylation resulted in higher ex vivo TNF mRNA following immune stimulation. Taken together, our findings link chronic stress and HPA axis regulation with epigenetic signatures at immune-related genes, thereby providing novel insights into how aberrant HPA axis function may contribute to heightened inflammation and disease risk.
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http://dx.doi.org/10.1016/j.bbi.2020.11.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897273PMC
February 2021

A call for social informatics.

J Am Med Inform Assoc 2020 11;27(11):1798-1801

Center for Health and Community, University of California, San Francisco, California, USA.

As evidence of the associations between social factors and health outcomes continues to mount, capturing and acting on social determinants of health (SDOH) in clinical settings has never been more relevant. Many professional medical organizations have endorsed screening for SDOH, and the U.S. Office of the National Coordinator for Health Information Technology has recommended increased capacity of health information technology to integrate and support use of SDOH data in clinical settings. As these efforts begin their translation to practice, a new subfield of health informatics is emerging, focused on the application of information technologies to capture and apply social data in conjunction with health data to advance individual and population health. Developing this dedicated subfield of informatics-which we term social informatics-is important to drive research that informs how to approach the unique data, interoperability, execution, and ethical challenges involved in integrating social and medical care.
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http://dx.doi.org/10.1093/jamia/ocaa175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671633PMC
November 2020

Framework for a Community Health Observing System for the Gulf of Mexico Region: Preparing for Future Disasters.

Front Public Health 2020 15;8:578463. Epub 2020 Oct 15.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States.

The Gulf of Mexico (GoM) region is prone to disasters, including recurrent oil spills, hurricanes, floods, industrial accidents, harmful algal blooms, and the current COVID-19 pandemic. The GoM and other regions of the U.S. lack sufficient baseline health information to identify, attribute, mitigate, and facilitate prevention of major health effects of disasters. Developing capacity to assess adverse human health consequences of future disasters requires establishment of a comprehensive, sustained community health observing system, similar to the extensive and well-established environmental observing systems. We propose a system that combines six levels of health data domains, beginning with three existing, national surveys and studies plus three new nested, longitudinal cohort studies. The latter are the unique and most important parts of the system and are focused on the coastal regions of the five GoM States. A statistically representative sample of participants is proposed for the new cohort studies, stratified to ensure proportional inclusion of urban and rural populations and with additional recruitment as necessary to enroll participants from particularly vulnerable or under-represented groups. Secondary data sources such as syndromic surveillance systems, electronic health records, national community surveys, environmental exposure databases, social media, and remote sensing will inform and augment the collection of primary data. Primary data sources will include participant-provided information via questionnaires, clinical measures of mental and physical health, acquisition of biological specimens, and wearable health monitoring devices. A suite of biomarkers may be derived from biological specimens for use in health assessments, including calculation of allostatic load, a measure of cumulative stress. The framework also addresses data management and sharing, participant retention, and system governance. The observing system is designed to continue indefinitely to ensure that essential pre-, during-, and post-disaster health data are collected and maintained. It could also provide a model/vehicle for effective health observation related to infectious disease pandemics such as COVID-19. To our knowledge, there is no comprehensive, disaster-focused health observing system such as the one proposed here currently in existence or planned elsewhere. Significant strengths of the GoM Community Health Observing System (CHOS) are its longitudinal cohorts and ability to adapt rapidly as needs arise and new technologies develop.
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http://dx.doi.org/10.3389/fpubh.2020.578463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593336PMC
October 2020

Measures of Psychosocial Stress and Stressful Exposures.

Arthritis Care Res (Hoboken) 2020 10;72 Suppl 10:676-685

University of California, San Francisco.

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http://dx.doi.org/10.1002/acr.24228DOI Listing
October 2020

Are long telomeres better than short? Relative contributions of genetically predicted telomere length to neoplastic and non-neoplastic disease risk and population health burden.

PLoS One 2020 8;15(10):e0240185. Epub 2020 Oct 8.

UCSF Department of Biochemistry and Biophysics, San Francisco, CA, United States of America.

Background: Mendelian Randomization (MR) studies exploiting single nucleotide polymorphisms (SNPs) predictive of leukocyte telomere length (LTL) have suggested that shorter genetically determined telomere length (gTL) is associated with increased risks of degenerative diseases, including cardiovascular and Alzheimer's diseases, while longer gTL is associated with increased cancer risks. These varying directions of disease risk have long begged the question: when it comes to telomeres, is it better to be long or short? We propose to operationalize and answer this question by considering the relative impact of long gTL vs. short gTL on disease incidence and burden in a population.

Methods And Findings: We used odds ratios (OR) of disease associated with gTL from a recently published MR meta-analysis to approximate the relative contributions of gTL to the incidence and burden of neoplastic and non-neoplastic disease in a European population. We obtained incidence data of the 9 cancers associated with long gTL and 4 non-neoplastic diseases associated with short gTL from the Institute of Health Metrics (IHME). Incidence rates of individual cancers from SEER, a database of United States cancer records, were used to weight the ORs in order to align with the available IHME data. These data were used to estimate the excess incidences due to long vs. short gTL, expressed as per 100,000 persons per standard deviation (SD) change in gTL. To estimate the population disease burden, we used the Disability Adjusted Life Years (DALY) metric from the IHME, a measure of overall disease burden that accounts for both mortality and morbidity, and similarly calculated the excess DALY associated with long vs. short gTL.

Results: Our analysis shows that, despite the markedly larger ORs of neoplastic disease, the large incidence of degenerative diseases causes the excess incidence attributable to gTL to balance that of neoplastic diseases. Long gTL is associated with an excess incidence of 94.04 cases/100,000 persons/SD (45.49-168.84, 95%CI) from the 9 cancer, while short gTL is associated with an excess incidence of 121.49 cases/100,000 persons/SD (48.40-228.58, 95%CI) from the 4 non-neoplastic diseases. When considering disease burden using the DALY metric, long gTL is associated with an excess 1255.25 DALYs/100,000 persons/SD (662.71-2163.83, 95%CI) due to the 9 cancers, while short gTL is associated with an excess 1007.75 DALYs/100,000 persons/SD (411.63-1847.34, 95%CI) due to 4 non-neoplastic diseases.

Conclusions: Our results show that genetically determined long and short telomere length are associated with disease risk and burden of approximately equal magnitude. These results provide quantitative estimates of the relative impact of genetically-predicted short vs. long TL in a human population, and provide evidence in support of the cancer-aging paradox, wherein human telomere length is balanced by opposing evolutionary forces acting to minimize both neoplastic and non-neoplastic diseases. Importantly, our results indicate that odds ratios alone can be misleading in different clinical scenarios, and disease risk should be assessed from both an individual and population level in order to draw appropriate conclusions about the risk factor's role in human health.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240185PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544094PMC
December 2020

A data-driven prospective study of dementia among older adults in the United States.

PLoS One 2020 7;15(10):e0239994. Epub 2020 Oct 7.

School of Medicine, Stanford University, Palo Alto, California, United States of America.

Background: Studies examining risk factors for dementia have typically focused on testing a priori hypotheses within specific risk factor domains, leaving unanswered the question of what risk factors across broad and diverse research fields may be most important to predicting dementia. We examined the relative importance of 65 sociodemographic, early-life, economic, health and behavioral, social, and genetic risk factors across the life course in predicting incident dementia and how these rankings may vary across racial/ethnic (non-Hispanic white and black) and gender (men and women) groups.

Methods And Findings: We conducted a prospective analysis of dementia and its association with 65 risk factors in a sample of 7,908 adults aged 51 years and older from the nationally representative US-based Health and Retirement Study. We used traditional survival analysis methods (Fine and Gray models) and a data-driven approach (random survival forests for competing risks) which allowed us to account for the semi-competing risk of death with up to 14 years of follow-up. Overall, the top five predictors across all groups were lower education, loneliness, lower wealth and income, and lower self-reported health. However, we observed variation in the leading predictors of dementia across racial/ethnic and gender groups such that at most four risk factors were consistently observed in the top ten predictors across the four demographic strata (non-Hispanic white men, non-Hispanic white women, non-Hispanic black men, non-Hispanic black women).

Conclusions: We identified leading risk factors across racial/ethnic and gender groups that predict incident dementia over a 14-year period among a nationally representative sample of US aged 51 years and older. Our ranked lists may be useful for guiding future observational and quasi-experimental research that investigates understudied domains of risk and emphasizes life course economic and health conditions as well as disparities therein.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239994PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540891PMC
December 2020

Anticipated and Experienced Ethnic/Racial Discrimination and Sleep: A Longitudinal Study.

Pers Soc Psychol Bull 2020 12 22;46(12):1724-1735. Epub 2020 Jun 22.

University of California, Santa Barbara, USA.

The transition to college is a stressful experience. For members of underrepresented minority groups, the usual stresses are frequently accompanied by ethnicity-based stressors, including discrimination. This longitudinal study extends prior work on discrimination by examining the prospective associations between anticipated and experienced ethnic/racial discrimination and sleep, a ubiquitous and basic biological need critical for optimal functioning. In a sample of 274 low-income/first-generation Latinx students, results from a cross-lagged panel model revealed that both the anticipation and experience of discrimination at the beginning of college uniquely predicted worsening sleep quality over the second half of freshmen year, controlling for relevant covariates. There was also some evidence for bidirectionality, with poor sleepers experiencing more discrimination. These findings add to the literature linking discrimination and sleep, both of which play large roles in mental, physical, social, and academic outcomes.
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http://dx.doi.org/10.1177/0146167220928859DOI Listing
December 2020

Is cellular energy monitoring more responsive to hypoxia than pulse oximetry?

Sleep Breath 2020 Dec 26;24(4):1633-1643. Epub 2020 May 26.

University of California San Francisco, San Francisco, CA, USA.

Purpose: Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. However, cellular energy monitoring (CE monitoring), a measure related to cellular hypoxia in the skin, is likely to be more responsive to inadequate breathing during sleep because during hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO for more vital organs. We carried out initial proof of concept testing to determine if CE monitoring has promise for being more responsive to hypoxic challenge occurring during sleep-disordered breathing (SDB) than pulse oximetry.

Methods: We assessed both CE monitoring and pulse oximetry in a series of conditions which affect oxygen supply: (1) breathing nitrogen or 100% oxygen, (2) physical exertion, and (3) studying a night of sleep in an individual known to be a loud snorer. We also present the results of a preliminary study comparing CE monitoring to pulse oximetry in eight individuals undergoing standard clinical overnight polysomnography for suspected SDB.

Results: CE monitoring is responsive to changes in cellular oxygen supply to the skin and detects hypoxia during SDB events that is not detected by pulse oximetry.

Conclusion: CE monitoring is a promising tool for identifying pathology at the mild end of the SDB spectrum.
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http://dx.doi.org/10.1007/s11325-020-02104-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679291PMC
December 2020

Longitudinal Associations of US Acculturation With Cognitive Performance, Cognitive Impairment, and Dementia.

Am J Epidemiol 2020 11;189(11):1292-1305

US Latinos, a growing, aging population, are disproportionately burdened by cognitive decline and dementia. Identification of modifiable risk factors is needed for interventions aimed at reducing risk. Broad sociocultural context may illuminate complex etiology among culturally diverse Latinos. Among 1,418 older (≥60 years), low-socioeconomic position (SEP) Latinos (predominantly of Mexican descent) in Sacramento, California, we examined whether US acculturation was associated with cognitive performance, cognitive decline, and dementia/ cognitive impairment without dementia over a 10-year period and whether education modified the associations (Sacramento Area Latino Study on Aging, 1998-2008). Analyses used linear mixed models, competing-risk regression, and inverse probability of censoring weights for attrition. Participants with high US acculturation had better cognitive performance (0.21 fewer cognitive errors at grand-mean-centered age 70 years) than those with low acculturation after adjustment for sociodemographic factors, practice effects, and survey language. Results may have been driven by cultural language use rather than identity factors (e.g., ethnic identity, interactions). Rate of cognitive decline and risk of dementia/cognitive impairment without dementia did not differ by acculturation, regardless of education (β = 0.00 (standard error, 0.00) and hazard ratio = 0.81 (95% confidence interval: 0.49, 1.35), respectively). High US acculturation was associated with better cognitive performance among these older, low-SEP Latinos. Acculturation may benefit cognition when SEP is low. Future studies should incorporate extended longitudinal assessments among more diverse groups.
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http://dx.doi.org/10.1093/aje/kwaa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604518PMC
November 2020

Longitudinal Associations of US Acculturation With Cognitive Performance, Cognitive Impairment, and Dementia.

Am J Epidemiol 2020 11;189(11):1292-1305

US Latinos, a growing, aging population, are disproportionately burdened by cognitive decline and dementia. Identification of modifiable risk factors is needed for interventions aimed at reducing risk. Broad sociocultural context may illuminate complex etiology among culturally diverse Latinos. Among 1,418 older (≥60 years), low-socioeconomic position (SEP) Latinos (predominantly of Mexican descent) in Sacramento, California, we examined whether US acculturation was associated with cognitive performance, cognitive decline, and dementia/ cognitive impairment without dementia over a 10-year period and whether education modified the associations (Sacramento Area Latino Study on Aging, 1998-2008). Analyses used linear mixed models, competing-risk regression, and inverse probability of censoring weights for attrition. Participants with high US acculturation had better cognitive performance (0.21 fewer cognitive errors at grand-mean-centered age 70 years) than those with low acculturation after adjustment for sociodemographic factors, practice effects, and survey language. Results may have been driven by cultural language use rather than identity factors (e.g., ethnic identity, interactions). Rate of cognitive decline and risk of dementia/cognitive impairment without dementia did not differ by acculturation, regardless of education (β = 0.00 (standard error, 0.00) and hazard ratio = 0.81 (95% confidence interval: 0.49, 1.35), respectively). High US acculturation was associated with better cognitive performance among these older, low-SEP Latinos. Acculturation may benefit cognition when SEP is low. Future studies should incorporate extended longitudinal assessments among more diverse groups.
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http://dx.doi.org/10.1093/aje/kwaa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604518PMC
November 2020

Better together: Sleep, circadian genes, and immunity.

Authors:
Aric A Prather

Brain Behav Immun 2020 07 6;87:201-202. Epub 2020 Apr 6.

Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, United States. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2020.04.011DOI Listing
July 2020

Temporal Links Between Self-Reported Sleep and Antibody Responses to the Influenza Vaccine.

Int J Behav Med 2021 Feb;28(1):151-158

Department of Psychology, Carnegie Mellon University, Pittsburgh, PA, USA.

Background: Growing evidence suggests that sleep plays an important role in immunological memory, including antibody responses to vaccination. However, much of the prior research has been carried out in the laboratory limiting the generalizability of the findings. Furthermore, no study has sought to identify sensitive periods prior to or after vaccination where sleep may have a stronger influence on antibody responses.

Methods: Eighty-three healthy young adults completed 13 days of sleep diaries and received the trivalent influenza vaccine on day 3 of the study. Measures of self-reported sleep duration, sleep efficiency, and subjective sleep quality were assessed on each day. Antibody levels to the influenza viral strains were quantified at baseline and 1 and 4 months following influenza vaccination.

Results: Shorter sleep duration, averaged over the collection period, was associated with fewer antibodies to the A/New Caledonia viral strain 1 and 4 months later, independent of baseline antibodies, age, sex, and cohort year. Analyses focused on nightly sleep on the days preceding and after the vaccination revealed that shorter sleep duration on the two nights before the vaccination predicted fewer antibodies 1 and 4 months later. Measures of self-reported sleep efficiency and subjective quality were unrelated to antibody responses to the influenza vaccination.

Conclusion: These findings provide further support for an association between sleep duration and antibody responses to the influenza vaccine and suggest that perhaps sleep on nights prior to vaccination are critical. If replicated, these findings may support sleep as a target for enhancing vaccination efficacy.
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http://dx.doi.org/10.1007/s12529-020-09879-4DOI Listing
February 2021

Telomere length analysis from minimally-invasively collected samples: Methods development and meta-analysis of the validity of different sampling techniques: American Journal of Human Biology.

Am J Hum Biol 2021 01 18;33(1):e23410. Epub 2020 Mar 18.

Department of Anthropology, University of Washington, Seattle, Washington, USA.

Objectives: Telomeres are the protective caps of chromosomes. They shorten with cell replication, age, and possibly environmental stimuli (eg, infection and stress). Short telomere length (TL) predicts subsequent worse health. Although venous whole blood (VWB) is most commonly used for TL measurement, other, more minimally invasive, sampling techniques are becoming increasingly common due to their field-friendliness, allowing for feasible measurement in low-resource contexts. We conducted statistical validation work for measuring TL in dried blood spots (DBS) and incorporated our results into a meta-analysis evaluating minimally invasive sampling techniques to measure TL.

Methods: We isolated DNA extracts from DBS using a modified extraction protocol and tested how they endured different shipping conditions and long-term cryostorage. We then included our in-house DBS TL validation statistics (correlation values with VWB TL and age) in a series of meta-analyses of results from 24 other studies that published similar associations for values between TL measured in DBS, saliva, and buccal cells.

Results: Our modified DBS extraction technique produced DNA yields that were roughly twice as large as previously recorded. Partially extracted DBS DNA was stable for 7 days at room temperature, and still provided reliable TL measurements, as determined by external validation statistics. In our meta-analysis, DBS TL had the highest external validity, followed by saliva, and then buccal cells-possibly reflecting similarities/differences in cellular composition vs VWB.

Conclusions: DBS DNA is the best proxy for VWB from the three minimally-invasively specimen types evaluated and can be used to expand TL research to diverse settings and populations.
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http://dx.doi.org/10.1002/ajhb.23410DOI Listing
January 2021

Efficacy of Digital Cognitive Behavioral Therapy for the Treatment of Insomnia Symptoms Among Pregnant Women: A Randomized Clinical Trial.

JAMA Psychiatry 2020 05;77(5):484-492

Department of Psychiatry, University of California, San Francisco, San Francisco.

Importance: Despite the prevalence and adverse consequences of prenatal insomnia, a paucity of research is available regarding interventions to improve insomnia symptoms during pregnancy.

Objective: To test the efficacy of digital cognitive behavioral therapy for insomnia (CBT-I) compared with standard treatment among pregnant women with insomnia symptoms.

Design, Setting, And Participants: This randomized clinical trial enrolled pregnant women from November 23, 2016, to May 22, 2018. Of the 2258 women assessed for eligibility using an online self-report questionnaire, 208 were randomized to receive digital CBT-I (n = 105) or standard treatment (n = 103) for insomnia. Participants were pregnant up to 28 weeks' gestation, and they either had elevated insomnia symptom severity or met the criteria for insomnia caseness as determined by self-report questionnaires. Participants completed outcome measures at 10 weeks (postintervention) and 18 weeks (follow-up) after randomization. All study visits were completed remotely, and the intervention was delivered digitally. Data were analyzed between December 12, 2018, and July 2, 2019.

Interventions: Digital CBT-I consisted of 6 weekly sessions of approximately 20 minutes each. Standard treatment reflected standard care. Women receiving standard treatment had no limits placed on the receipt of nonstudy treatments, including medication and psychotherapy.

Main Outcomes And Measures: All outcomes were assessed remotely using self-report questionnaires administered via online survey. The primary outcome was the change in insomnia symptom severity (measured by the Insomnia Severity Index) from baseline to postintervention. Secondary outcomes were sleep efficiency and nightly sleep duration (defined by sleep diary), global sleep quality (measured by the Pittsburgh Sleep Quality Index), depressive symptom severity (measured by the Edinburgh Postnatal Depression Scale), and anxiety symptom severity (measured by the Generalized Anxiety Disorder Scale-7). For each outcome, we also examined the change from baseline to follow-up.

Results: The 208 participants had a mean (SD) age of 33.6 (3.7) years and a mean (SD) gestational age of 17.6 (6.3) weeks at baseline. Most of the participants were white (138 [66.3%]), married or cohabiting (196 [94.2%]), had a college degree (180 [86.5%]), and earned $100 000 or more per year (141 [67.8%]). Women randomized to receive digital CBT-I experienced statistically significantly greater improvements in insomnia symptom severity from baseline to postintervention compared with women randomized to receive standard treatment (time-by-group interaction, difference = -0.36; 95% CI, -0.48 to -0.23; χ2 = 29.8; P < .001; d = -1.03). Improvements from baseline to postintervention for all secondary outcomes, with the exception of sleep duration, were statistically significant. A similar pattern of results was evident for the change from baseline to follow-up.

Conclusions And Relevance: In this trial, digital CBT was an effective, scalable, safe, and acceptable intervention for improving insomnia symptoms during pregnancy.

Trial Registration: ClinicalTrials.gov identifier: NCT02805998.
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http://dx.doi.org/10.1001/jamapsychiatry.2019.4491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990703PMC
May 2020

Perfect timing: circadian rhythms, sleep, and immunity - an NIH workshop summary.

JCI Insight 2020 01 16;5(1). Epub 2020 Jan 16.

Department of Immunology and Microbiology, Scripps Research Institute, Jupiter, Florida, USA.

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses - ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation.
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http://dx.doi.org/10.1172/jci.insight.131487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030790PMC
January 2020

Exposures to structural racism and racial discrimination among pregnant and early post-partum Black women living in Oakland, California.

Stress Health 2020 Apr 23;36(2):213-219. Epub 2020 Jan 23.

Family Health Care Nursing Department, University of California, San Francisco, San Francisco, California.

Research supports that exposure to stressors (e.g., perceived stress and racism) during pregnancy can negatively impact the immune system, which may lead to infection and ultimately increases the risk for having a preterm or low-birthweight infant. It is well known that Black women report higher levels of stressors at multiple timepoints across pregnancy compared with women of all other racial and ethnic groups. This study addresses gaps in the literature by describing pregnant and early post-partum Black women's exposures to structural racism and self-reported experiences of racial discrimination, and the extent to which these factors are related. We used a cross-sectional study design to collect data related to exposures to racism from pregnant and early post-partum Black women residing in Oakland, California, from January 2016 to December 2017. Comparative analysis revealed that living in highly deprived race + income neighborhoods was associated with experiencing racial discrimination in three or more situational domains (p = .01). Findings show that Black women are exposed to high levels of racism that may have negative impacts on maternal health outcomes.
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http://dx.doi.org/10.1002/smi.2922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269549PMC
April 2020

Part I: A Quantitative Study of Social Risk Screening Acceptability in Patients and Caregivers.

Am J Prev Med 2019 12;57(6 Suppl 1):S25-S37

Department of Family & Community Medicine, University of California, San Francisco, San Francisco, California.

Introduction: Despite recent growth in healthcare delivery-based social risk screening, little is known about patient perspectives on these activities. This study evaluates patient and caregiver acceptability of social risk screening.

Methods: This was a cross-sectional survey of 969 adult patients and adult caregivers of pediatric patients recruited from 6 primary care clinics and 4 emergency departments across 9 states. Survey items included the Center for Medicare and Medicaid Innovation Accountable Health Communities' social risk screening tool and questions about appropriateness of screening and comfort with including social risk data in electronic health records. Logistic regressions evaluated covariate associations with acceptability measures. Data collection occurred from July 2018 to February 2019; data analyses were conducted in February‒March 2019.

Results: Screening was reported as appropriate by 79% of participants; 65% reported comfort including social risks in electronic health records. In adjusted models, higher perceived screening appropriateness was associated with previous exposure to healthcare-based social risk screening (AOR=1.82, 95% CI=1.16, 2.88), trust in clinicians (AOR=1.55, 95% CI=1.00, 2.40), and recruitment from a primary care setting (AOR=1.70, 95% CI=1.23, 2.38). Lower appropriateness was associated with previous experience of healthcare discrimination (AOR=0.66, 95% CI=0.45, 0.95). Higher comfort with electronic health record documentation was associated with previously receiving assistance with social risks in a healthcare setting (AOR=1.47, 95% CI=1.04, 2.07).

Conclusions: A strong majority of adult patients and caregivers of pediatric patients reported that social risk screening was appropriate. Most also felt comfortable including social risk data in electronic health records. Although multiple factors influenced acceptability, the effects were moderate to small. These findings suggest that lack of patient acceptability is unlikely to be a major implementation barrier.

Supplement Information: This article is part of a supplement entitled Identifying and Intervening on Social Needs in Clinical Settings: Evidence and Evidence Gaps, which is sponsored by the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services, Kaiser Permanente, and the Robert Wood Johnson Foundation.
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http://dx.doi.org/10.1016/j.amepre.2019.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336892PMC
December 2019

Pregnant Patient Perceptions of Provider Detection and Treatment of Insomnia.

Behav Sleep Med 2020 Nov-Dec;18(6):787-796. Epub 2019 Nov 6.

Department of Psychiatry, University of California , San Francisco.

: To survey pregnant patients about whether their health care providers assessed insomnia, the types of treatment recommendations providers made, and the types of treatments patients utilized. : Participants were 423 English-speaking pregnant women. : In this cross-sectional study, participants self-reported insomnia symptoms on the Insomnia Severity Index and indicated whether they discussed their sleep with a health care provider, whether they received any recommendations to improve their sleep, and whether they utilized any interventions or aids to improve their sleep during their current pregnancy. : Approximately one-third (39%) of participants reported that they discussed their sleep with a health care provider at some point during their pregnancy. Among participants who reported moderate to severe insomnia symptoms (Insomnia Severity Index>14), 57% reported that they had discussed their sleep with a health care provider, and 28% reported receiving an insomnia diagnosis. Over-the-counter medication was the most commonly recommended (53%) and utilized (39%) sleep intervention among women with moderate to severe insomnia symptoms. : According to patient report, insomnia may be under-detected during pregnancy. When insomnia is recognized, treatment recommendations do not match clinical practice guidelines or women's preferences for receiving cognitive behavior therapy for insomnia. Taken together with previous research on the prevalence and consequences of prenatal insomnia, these findings suggest the need for an increased focus on the importance of sleep during pregnancy.
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http://dx.doi.org/10.1080/15402002.2019.1688153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200275PMC
February 2021

The assessment and management of insomnia: an update.

World Psychiatry 2019 Oct;18(3):337-352

Department of Neurology, University of California San Francisco School of Medicine, San Francisco, CA, USA.

Insomnia poses significant challenges to public health. It is a common condition associated with marked impairment in function and quality of life, psychiatric and physical morbidity, and accidents. As such, it is important that effective treatment is provided in clinical practice. To this end, this paper reviews critical aspects of the assessment of insomnia and the available treatment options. These options include both non-medication treatments, most notably cognitive behavioral therapy for insomnia, and a variety of pharmacologic therapies such as benzodiazepines, "z-drugs", melatonin receptor agonists, selective histamine H1 antagonists, orexin antagonists, antidepressants, antipsychotics, anticonvulsants, and non-selective antihistamines. A review of the available research indicates that rigorous double-blind, randomized, controlled trials are lacking for some of the most commonly administered insomnia therapies. However, there are an array of interventions which have been demonstrated to have therapeutic effects in insomnia in trials with the above features, and whose risk/benefit profiles have been well characterized. These interventions can form the basis for systematic, evidence-based treatment of insomnia in clinical practice. We review this evidence base and highlight areas where more studies are needed, with the aim of providing a resource for improving the clinical management of the many patients with insomnia.
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http://dx.doi.org/10.1002/wps.20674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732697PMC
October 2019

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Mol Psychiatry 2020 05 27;25(5):1141-1153. Epub 2019 Aug 27.

School of Kinesiology, University of British Columbia, War Memorial Gymnasium, Room 210, 6081 University Boulevard, Vancouver, BC, V6T 1Z1, Canada.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals.
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http://dx.doi.org/10.1038/s41380-019-0482-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044034PMC
May 2020

Sleep Pharmacogenetics: The Promise of Precision Medicine.

Sleep Med Clin 2019 Sep 14;14(3):317-331. Epub 2019 Jun 14.

University of California San Francisco, San Francisco, CA, USA.

Pharmacogenetics is the branch of personalized medicine concerned with the variability in drug response occurring because of heredity. Advances in genetics research, and decreasing costs of gene sequencing, are promoting tremendous growth in pharmacogenetics in all areas of medicine, including sleep medicine. This article reviews the body of research indicating that there are genetic variations that affect the therapeutic actions and adverse effects of agents used for the treatment of sleep disorders to show the potential of pharmacogenetics to improve the clinical practice of sleep medicine.
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http://dx.doi.org/10.1016/j.jsmc.2019.05.003DOI Listing
September 2019

Socioeconomic Status, Preeclampsia Risk and Gestational Length in Black and White Women.

J Racial Ethn Health Disparities 2019 12 31;6(6):1182-1191. Epub 2019 Jul 31.

California Preterm Birth Initiative, University of California San Francisco, San Francisco, CA, USA.

Background: Higher socioeconomic status (SES) has less impact on cardio-metabolic disease and preterm birth risk among Black women compared to White women, an effect called "diminishing returns." No studies have tested whether this also occurs for pregnancy cardio-metabolic disease, specifically preeclampsia, or whether preeclampsia risk could account for race-by-SES disparities in birth timing.

Methods: A sample of 718,604 Black and White women was drawn from a population-based California cohort of singleton births. Education, public health insurance status, gestational length, and preeclampsia diagnosis were extracted from a State-maintained birth cohort database. Age, prenatal care, diabetes diagnosis, smoking during pregnancy, and pre-pregnancy body mass index were covariates.

Results: In logistic regression models predicting preeclampsia risk, the race-by-SES interaction (for both education and insurance status) was significant. White women were at lower risk for preeclampsia, and higher SES further reduced risk. Black women were at higher risk for preeclampsia, and SES did not attenuate risk. In pathway analyses predicting gestational length, an indirect effect of the race-by-SES interaction was observed. Among White women, higher SES predicted lower preeclampsia risk, which in turn predicted longer gestation. The same was not observed for Black women.

Conclusions: Compared to White women, Black women had increased preeclampsia risk. Higher SES attenuated risk for preeclampsia among White women, but not for Black women. Similarly, higher SES indirectly predicted longer gestational length via reduced preeclampsia risk among White women, but not for Black women. These findings are consistent with diminishing returns of higher SES for Black women with respect to preeclampsia.
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http://dx.doi.org/10.1007/s40615-019-00619-3DOI Listing
December 2019

Sleep debt: the impact of weekday sleep deprivation on cardiovascular health in older women.

Sleep 2019 10;42(10)

Division of Cardiology, Department of Medicine, University of California, San Francisco, CA.

Study Objectives: Short sleep duration is associated with increased cardiovascular disease (CVD) risk. However, it is uncertain whether sleep debt, a measure of sleep deficiency during the week compared to the weekend, confers increased cardiovascular risk. Because sleep disturbances increase with age particularly in women, we examined the relationship between sleep debt and ideal cardiovascular health (ICH) in older women.

Methods: Sleep debt is defined as the difference between self-reported total weekday and weekend sleep hours of at least 2 hours among women without apparent CVD and cancer participating in the Women's Health Stress Study follow-up cohort of female health professionals (N = 22 082). The ICH consisted of seven health factors and behaviors as defined by the American Heart Association Strategic 2020 goals including body mass index, smoking, physical activity, diet, blood pressure, total cholesterol, and glucose.

Results: Mean age was 72.1 ± 6.0 years. Compared to women with no sleep debt, women with sleep debt were more likely to be obese and have hypertension (pall < .05). Linear regression models adjusted for age and race/ethnicity revealed that sleep debt was significantly associated with poorer ICH (B = -0.13 [95% CI = -0.18 to -0.08]). The relationship was attenuated but remained significant after adjustment for education, income, depression/anxiety, cumulative stress, and snoring.

Conclusion: Sleep debt was associated with poorer ICH, despite taking into account socioeconomic status and psychosocial factors. These results suggest that weekly sleep duration variation, possibly leading to circadian misalignment, may be associated with cardiovascular risk in older women.
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http://dx.doi.org/10.1093/sleep/zsz149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783901PMC
October 2019

Association of Social and Behavioral Risk Factors With Earlier Onset of Adult Hypertension and Diabetes.

JAMA Netw Open 2019 05 3;2(5):e193933. Epub 2019 May 3.

Department of Pediatrics, University of California, San Francisco.

Importance: The National Academy of Medicine has recommended incorporating information on social and behavioral factors associated with health, such as educational level and exercise, into electronic health records, but questions remain about the clinical value of doing so.

Objective: To examine whether National Academy of Medicine-recommended social and behavioral risk factor domains are associated with earlier onset of hypertension and/or diabetes in a clinical population.

Design, Setting, And Participants: This prospective cohort study used data collected from April 1, 2005, to December 31, 2016, from a population-based sample of 41 745 patients from 4 cycles of Kaiser Permanente Northern California's Adult Member Health Survey, administered to members at 19 Kaiser Permanente Northern California medical center service populations. The study used Kaplan-Meier survival tables and Cox proportional hazards regression analysis to estimate the onset of hypertension and diabetes among patients with no indication of disease at baseline. Data analysis was performed from June 2, 2017, to March 26, 2019.

Exposures: Race/ethnicity, educational level, financial worry, partnership status, stress, intimate partner violence, concentrated neighborhood poverty, depressive symptoms, infrequent exercise, smoking, heavy alcohol consumption, and cumulative social and behavioral risk.

Main Outcomes And Measures: Onset of hypertension and diabetes during the 3.5 years after survey administration.

Results: The study included 18 133 people without baseline hypertension (mean [SD] age, 48.1 [15.3] years; 10 997 [60.7%] female; and 11 503 [63.4%] white) and 35 788 people without baseline diabetes (mean [SD] age, 56.2 [16.9] years; 20 191 [56.4%] female; and 24 351 [68.0%] white). There was a dose-response association between the number of social and behavioral risk factors and likelihood of onset of each condition. Controlling for age, sex, race/ethnicity, body mass index, and survey year, hazard ratios (HRs) comparing those with 3 or more risk factors with those with 0 risk factor were 1.41 (95% CI, 1.17-1.71) for developing hypertension and 1.53 (95% CI, 1.29-1.82) for developing diabetes. When the same covariates were adjusted for, having less than a high school educational level (hazard ratio [HR], 1.84; 95% CI, 1.40-2.43), being widowed (HR, 1.38; 95% CI, 1.11-1.71), concentrated neighborhood poverty (HR, 1.26; 95% CI, 1.00-1.59), infrequent exercise (HR, 1.22; 95% CI, 1.08-1.38), and smoking (HR, 1.35; 95% CI, 1.10-1.67) were significantly associated with hypertension onset. Having less than a high school educational level (HR, 1.58; 95% CI, 1.26-1.97), financial worry (HR, 1.29; 95% CI, 1.13-1.46), being single or separated (HR, 1.24; 95% CI, 1.08-1.42), high stress (HR, 1.28; 95% CI, 1.09-1.51), intimate partner violence (HR, 1.68; 95% CI, 1.14-2.48), concentrated neighborhood poverty (HR, 1.31; 95% CI, 1.07-1.60), depressive symptoms (HR, 1.28; 95% CI, 1.10-1.50), and smoking (HR, 1.53; 95% CI, 1.27-1.86) were significantly associated with diabetes onset, although heavy alcohol consumption was associated with protection (HR, 0.75; 95% CI, 0.66-0.85) rather than risk.

Conclusions And Relevance: Independent of traditional risk factors, individual and cumulative social and behavioral risk factor exposures were associated with onset of hypertension and diabetes within 3.5 years in a clinical setting. The findings support the value of assessing social and behavioral risk factors to help identify high-risk patients and of providing targets for intervention.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.3933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537925PMC
May 2019

Obstructive sleep apnea, nighttime arousals, and leukocyte telomere length: the Multi-Ethnic Study of Atherosclerosis.

Sleep 2019 07;42(7)

Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Study Objectives: Sleep disturbances and sleep apnea are associated with increased vulnerability to age-related disease, altering molecular pathways affecting biological aging. Telomere length captures one component of biological aging. We evaluated whether objectively assessed sleep and sleep apnea relate to leukocyte telomere length (LTL) in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Men and women aged 44-84 years (n = 672) from the MESA Stress and MESA Sleep studies underwent polysomnography and 7 day actigraphy (at Exam 5) and assessment of LTL (at baseline [Exam 1] and about 10 years later [Exam 5]).

Results: General linear models adjusting for age, sex, race/ethnicity, BMI, physical activity, and smoking found that severe obstructive sleep apnea (OSA; apnea-hypopnea index > 30) was cross-sectionally associated with shorter LTL (p = 0.007). Modest associations of shorter LTL with less rapid eye movement sleep, more stage 1 sleep, wake after sleep onset >30 min, and long sleep duration were found, but these effects were diminished after adjusting for lifestyle and OSA. Exploratory analyses found that higher arousal index at Exam 5 was associated with greater LTL decline over the prior 10 years (p = 0.004).

Conclusions: OSA was associated with shorter LTL. Individuals with high-arousal frequency had greater leukocyte telomere attrition over the prior decade. These findings suggest that sleep apnea and sleep fragmentation are associated with accelerated biological aging.
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http://dx.doi.org/10.1093/sleep/zsz089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612669PMC
July 2019

Assessment of Sleep Disturbances and Exhaustion in Mothers of Children With Atopic Dermatitis.

JAMA Dermatol 2019 05;155(5):556-563

Department of Dermatology Program for Clinical Research, University of California, San Francisco.

Importance: The well-being and development of children is strongly influenced by parents' physical and psychosocial health. Data from small, clinic-based studies suggest that sleep loss may be common in parents of children with atopic dermatitis (AD), but longitudinal population-based studies are lacking.

Objectives: To compare sleep disturbances over time between mothers of children with and without AD and to determine whether these disturbances are associated with the child's disease severity and the child's sleep disturbances.

Design, Setting, And Participants: In the ongoing Avon Longitudinal Study of Parents and Children, all pregnant women residing in Avon, United Kingdom, with an expected delivery date between April 1, 1991, and December 31, 1992, were recruited. Analyses for this study, a secondary analysis of this cohort, were performed from September 2017 to September 2018. Mother-child pairs were followed up with a time-varying measure of child AD activity and severity and self-reported maternal sleep measures repeated at multiple time points between child ages 6 months and 11 years.

Main Outcomes And Measures: Time-varying binary measures of maternal sleep duration (<6 vs ≥6 hours per night), difficulty falling asleep, early morning awakening, subjectively insufficient sleep, and daytime exhaustion.

Results: The study followed up 13 988 mother-child pairs from birth for a median duration of 11 (interquartile range, 7-11) years. Among the cohort, 11 585 of 13 972 mothers (82.9%) were aged 21 to 34 years and 12 001 of 12 324 (97.4%) were of white race/ethnicity; 7220 of 13 978 children (51.7%) were male. Sleep duration (adjusted odds ratio [AOR], 1.09; 95% CI, 0.90-1.32) and early morning awakenings (AOR, 1.16; 95% CI, 0.93-1.46) were similar between mothers of children with and without AD. In contrast, mothers of children with AD were more likely to report difficulty falling asleep (AOR, 1.36; 95% CI, 1.01-1.83), subjectively insufficient sleep (AOR, 1.43; 95% CI, 1.24-1.66), and daytime exhaustion (AOR, 1.41; 95% CI, 1.12-1.78) independent of the child's comorbid asthma and/or allergic rhinitis. For all measures, worse child AD severity was associated with worse maternal sleep outcomes. The magnitude and significance of the associations were largely unchanged after adjustment for child sleep disturbances.

Conclusions And Relevance: Mothers of children with AD reported difficulty falling asleep, subjectively insufficient sleep, and daytime exhaustion throughout the first 11 years of childhood. However, child sleep disturbances did not fully explain maternal sleep disturbances, and future research should investigate other mechanisms. In caring for children with AD, clinicians should consider maternal sleep disturbances and caregiver fatigue.
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http://dx.doi.org/10.1001/jamadermatol.2018.5641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506883PMC
May 2019