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BACKGROUND: Abnormalities in dorsolateral prefrontal cortex (DLPFC) oscillations are neurophysiological signatures of schizophrenia thought to underlie its cognitive deficits. Transcranial magnetic stimulation with electroencephalography (TMS-EEG) provides a measure of cortical oscillations unaffected by sensory relay functionality and/or patients' level of engagement, which are important confounding factors in schizophrenia. Previous TMS-EEG work showed reduced fast, gamma-range oscillations and a slowing of the main DLPFC oscillatory frequency, or natural frequency, in chronic schizophrenia. However, it is unclear whether this DLPFC natural frequency slowing is present in early-course schizophrenia (EC-SCZ) and is associated with symptom severity and cognitive dysfunction. METHODS: We applied TMS-EEG to the left DLPFC in 30 EC-SCZ and 28 healthy control (HC) subjects. Goal-directed working memory performance was assessed using the "AX" Continuous Performance Task (AX-CPT). The EEG frequency with the highest cumulative power at the stimulation site, or natural frequency, was extracted. We also calculated the local Relative Spectral Power (RSP) as the average power in each frequency band divided by the broadband power. RESULTS: Compared to HC, EC-SCZ had reduced DLPFC natural frequency (p=0.0000002, Cohen's d=-2.32) and higher DLPFC beta-range RSP (p=0.0003, Cohen's d=0.77). In EC-SCZ, the DLPFC natural frequency was inversely associated with negative symptoms. Across all participants, the beta-band RSP negatively correlated with the AX-CPT performance. CONCLUSIONS: A DLPFC oscillatory slowing is an early pathophysiological biomarker of schizophrenia that is associated with its symptom severity and cognitive impairments. Future work should assess whether non-invasive neurostimulation can ameliorate prefrontal oscillatory deficits and related clinical functions in EC-SCZ.
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Low power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We quantified the statistical power and magnitude error of studies of epilepsy surgery outcomes. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4 (median odds ratio 9.3 vs. median true odds ratio 1.7), while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6 (2.7 vs. 1.7). We conclude that Bayesian estimation of odds ratio attenuates the exaggeration of significant effect sizes in underpowered studies. This approach could help improve patient counseling about the chance of seizure freedom after epilepsy surgery.
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OBJECTIVES: Many sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance. METHODS: The outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions. RESULTS: In individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with â¼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility. CONCLUSION: The strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition.
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Cognición , Hispánicos o Latinos , Sueño , Humanos , Femenino , Masculino , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Persona de Mediana Edad , Vigilia , Ritmo CircadianoRESUMEN
Background: Late-life depression is characterized by disability, cognitive impairment and decline, and a high risk of recurrence following remission. Aside from past psychiatric history, prognostic neurobiological and clinical factors influencing recurrence risk are unclear. Moreover, it is unclear if cognitive impairment predisposes to recurrence, or whether recurrent episodes may accelerate brain aging and cognitive decline. The purpose of the REMBRANDT study (Recurrence markers, cognitive burden, and neurobiological homeostasis in late-life depression) is to better elucidate these relationships and identify phenotypic, cognitive, environmental, and neurobiological factors contributing to and predictive of depression recurrence. Methods: Across three sites, REMBRANDT will enroll 300 depressed elders who will receive antidepressant treatment. The goal is to enroll 210 remitted depressed participants and 75 participants with no mental health history into a two-year longitudinal phase focusing on depression recurrence. Participants are evaluated every 2 months with deeper assessments occurring every 8 months, including structural and functional neuroimaging, environmental stress assessments, deep symptom phenotyping, and two weeks of 'burst' ecological momentary assessments to elucidate variability in symptoms and cognitive performance. A broad neuropsychological test battery is completed at the beginning and end of the longitudinal study. Significance: REMBRANDT will improve our understanding of how alterations in neural circuits and cognition that persist during remission contribute to depression recurrence vulnerability. It will also elucidate how these processes may contribute to cognitive impairment and decline. This project will obtain deep phenotypic data that will help identify vulnerability and resilience factors that can help stratify individual clinical risk.
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STUDY OBJECTIVES: To help prioritize target/groups for experimental intervention studies, we characterized cross-sectional associations between 24-hour sleep-wake measures and depression symptoms, and evaluated if similar sleep-wake-depression relationships existed in people with and without higher insomnia severity. METHODS: Participants had ≥3 days of actigraphy data (nâ =â 1884; mean ageâ =â 68.6/SDâ =â 9.1; 54.1% female). We extracted 18 sleep, activity, timing, rhythmicity, and fragmentation measures from actigraphy. We used individual and multivariable regressions with the outcome of clinically significant depression symptoms (Center for Epidemiologic Studies Depression Scaleâ ≥â 16). We conducted sensitivity analyses in people with higher insomnia severity (top quartile of the Women's Health Initiative Insomnia Rating Scale total score). RESULTS: From separate models in the overall sample, the odds of having depression symptoms were higher with: later timing (e.g. activity onset time odds ratio [OR]/1 SDâ =â 1.32; 95% confidence interval [CI]: 1.16 to 1.50), lower rhythmicity (e.g. pseudo-F OR/1 SDâ =â 0.75; 95% CI: 0.66 to 0.85), less activity (e.g. amplitude OR/1 SDâ =â 0.83; 95% CI: 0.72 to 0.95), and worse insomnia (OR/1 SDâ =â 1.48, 95% CI: 1.31 to 1.68). In multivariable models conducted among people with lower insomnia severity, later timing, lower rhythmicity, and higher insomnia severity were independent correlates of depression. In people with higher insomnia symptom severity, measures of later timing were most strongly associated with depression symptoms. CONCLUSIONS: These correlative observations suggest that experimental studies are warranted to test if: broadly promoting 24-hour sleep-wake functioning reduces depression even in people without severe insomnia, and if advancing timing leads to depression symptom reductions in people with insomnia.
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Aterosclerosis , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Femenino , Anciano , Masculino , Depresión/complicaciones , Depresión/diagnóstico , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Estudios Transversales , SueñoRESUMEN
OBJECTIVE: Perform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms. DESIGN: Secondary analysis of a randomized controlled trial with convenience age subsamples (younger (20-49 year; n = 52) versus and older (50-71 years; n = 35)). SETTING: Community mental health clinics. PARTICIPANTS: Eighty-seven adults with serious mental illness. INTERVENTION: TranS-C versus treatment as usual (TAU). MEASUREMENTS: Outcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude). RESULTS: Depression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ2 = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = -0.40, 95% confidence interval (CI): -0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: -0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = -0.52, n = 15, p = 0.049). CONCLUSION: Confirmatory trials are needed, given the low age-specific sample sizes here, to determine if TranS -C's produces durable depression responses by increasing sleep-wake rhythm stability in older adults and improving insomnia symptoms in younger adults. BRIEF ARTICLE SUMMARY: The authors evaluated preliminary efficacy of a behavioral intervention that targets sleep/sleep-wake rhythms, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms in people with serious mental illness. TranS-C was associated with higher depression response rates than treatment as usual 6-months postintervention. The degree of depression symptom response 6-months later was related to the degree of treatment phase improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults). A pragmatic nonpharmacologic intervention, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction, has preliminary efficacy for improving sleep-wake factors and depression symptoms.
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Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Anciano , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Depresión/terapia , Depresión/psicología , Sueño/fisiología , Resultado del TratamientoRESUMEN
OBJECTIVE: To identify 1) complicated grief symptom clusters among acutely-bereaved older adults who have lost a spouse to COVID-19 and 2) if spousal death due to COVID-19 increased risk of developing probable PGD METHODS: Eighty adults participating in a randomized controlled trial for depression prevention (mean age [± SD] = 70.4 [6.6]) completed the Inventory of Complicated Grief, every 3 months over a maximum of 15 months. Twenty-four percent (n = 19) of participants lost a spouse to COVID-19; 76% (n = 61) lost a spouse to other causes of death. Adjusted linear regression examined the associations between COVID-19 bereavement and six symptom clusters: yearning and preoccupation, anger and bitterness, shock and disbelief, estrangement from others, hallucinations, and behavior change. RESULTS: Compared to the non-COVID-19 group, the COVID-19 bereaved group reported greater shock and disbelief, hallucinations of the deceased, and estrangement from others. COVID-19 death was also associated with higher risk for probable prolonged grief disorder (PGD) at 12 months (odds ratio = 4.38, p = 0.027). CONCLUSIONS: Older adults who have lost a spouse to COVID-19 present with specific symptoms of distress and may eventually require clinical care for PGD.
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Aflicción , COVID-19 , Humanos , Anciano , Trastorno de Duelo Prolongado , Síndrome , Pesar , AlucinacionesRESUMEN
With rapid development of techniques to measure brain activity and structure, statistical methods for analyzing modern brain-imaging data play an important role in the advancement of science. Imaging data that measure brain function are usually multivariate high-density longitudinal data and are heterogeneous across both imaging sources and subjects, which lead to various statistical and computational challenges. In this article, we propose a group-based method to cluster a collection of multivariate high-density longitudinal data via a Bayesian mixture of smoothing splines. Our method assumes each multivariate high-density longitudinal trajectory is a mixture of multiple components with different mixing weights. Time-independent covariates are assumed to be associated with the mixture components and are incorporated via logistic weights of a mixture-of-experts model. We formulate this approach under a fully Bayesian framework using Gibbs sampling where the number of components is selected based on a deviance information criterion. The proposed method is compared to existing methods via simulation studies and is applied to a study on functional near-infrared spectroscopy, which aims to understand infant emotional reactivity and recovery from stress. The results reveal distinct patterns of brain activity, as well as associations between these patterns and selected covariates.
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Teorema de Bayes , Humanos , Estudios Longitudinales , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Espectroscopía Infrarroja Corta/métodos , Interpretación Estadística de Datos , Modelos Estadísticos , Lactante , Análisis Multivariante , Bioestadística/métodosRESUMEN
Nocturia (waking to void) is prevalent among older adults. Disruption of the well-described circadian rhythm in urine production with higher nighttime urine output is its most common cause. In young adults, their circadian rhythm is modulated by the 24-h secretory pattern of hormones that regulate salt and water excretion, including antidiuretic hormone (ADH), renin, angiotensin, aldosterone, and atrial natriuretic peptide (ANP). The pattern of hormone secretion is less clear in older adults. We investigated the effect of sleep on the 24-h secretion of these hormones in healthy older adults. Thirteen participants aged ≥65 yr old underwent two 24-h protocols at a clinical research center 6 wk apart. The first used a habitual wake-sleep protocol, and the second used a constant routine protocol that removed the influence of sleep, posture, and diet. To assess hormonal rhythms, plasma was collected at 8:00 am, 12:00 pm, 4:00 pm, and every 30 min from 7:00 pm to 7:00 am. A mixed-effects regression model was used to compare subject-specific and mean trajectories of hormone secretion under the two conditions. ADH, aldosterone, and ANP showed a diurnal rhythm that peaked during sleep in the wake-sleep protocol. These nighttime elevations were significantly attenuated within subjects during the constant routine. We conclude that sleep has a masking effect on circadian rhythm amplitude of ADH, aldosterone, and ANP: the amplitude of each is increased in the presence of sleep and reduced in the absence of sleep. Disrupted sleep could potentially alter nighttime urine output in healthy older adults via this mechanism.NEW & NOTEWORTHY Nocturia (waking to void) is the most common cause of sleep interruption among older adults, and increased nighttime urine production is its primary etiology. We showed that in healthy older adults sleep affects the 24-h secretory rhythm of hormones that regulate salt-water balance, which potentially alters nighttime urine output. Further studies are needed to elucidate the impact of chronic insomnia on the secretory rhythms of these hormones.
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Aldosterona , Nocturia , Adulto Joven , Humanos , Anciano , Micción , Sueño/fisiología , Ritmo Circadiano , PoliuriaRESUMEN
Objective: Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk. Methods: Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [18F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress. Results: Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004). Conclusions: These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.
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Shift workers experience poor sleep and dysregulated cardiac autonomic function during sleep. However, it is unknown if this dysregulation persists into retirement, potentially accelerating the age-associated risk for adverse cardiovascular outcomes. Using sleep deprivation as a physiological challenge to cardiovascular autonomic function, we compared heart rate (HR) and high-frequency heart rate variability (HF-HRV) during baseline and recovery sleep following sleep deprivation between retired night shift and day workers. Participants were retired night shift (N = 33) and day workers (N = 37) equated on age (mean [standard deviation] = 68.0 [5.6] years), sex (47% female), race/ethnicity (86% White), and body mass index. Participants completed a 60-h lab protocol including one night of baseline polysomnography-monitored sleep, followed by 36 h of sleep deprivation and one night of recovery sleep. Continuously recorded HR was used to calculate HF-HRV. Linear mixed models compared HR and HF-HRV during non-rapid eye movement (NREM) and REM sleep between groups during baseline and recovery nights. Groups did not differ on HR or HF-HRV during NREM or REM sleep (ps > .05) and did not show differential responses to sleep deprivation. In the full sample, HR increased and HF-HRV decreased from baseline to recovery during NREM (ps < .05) and REM (ps < .01). Both groups exhibited cardiovascular autonomic changes during recovery sleep following 36 h of sleep deprivation. Sleep deprivation appears to induce cardiovascular autonomic changes that persist into recovery sleep in older adults, regardless of shift work history.
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Jubilación , Privación de Sueño , Humanos , Femenino , Anciano , Preescolar , Masculino , Frecuencia Cardíaca/fisiología , Sistema Nervioso Autónomo/fisiología , Corazón , SueñoRESUMEN
STUDY OBJECTIVES: Shift work is associated with compromised cognitive function, and with chronic exposure, may place shift workers at elevated risk for dementia. However, evidence of cognitive impairment among former night shift workers is mixed, possibly due to inconsistencies regarding retirement status, work history classification, and cognitive assessments. To address these limitations, this study compared neurocognitive function between retired night shift workers and retired day workers using a well-characterized sample and a rigorous neurocognitive test battery. METHODS: Participants (Nâ =â 61; mean age: 67.9 ± 4.7 years; 61% females; 13% non-white) were 31 retired day workers and 30 retired night shift workers equated on age, sex, race/ethnicity, premorbid IQ, years retired, and diary-assessed habitual sleep characteristics. Participants completed a neurocognitive battery assessing six cognitive domains (language, visuospatial ability, attention, immediate and delayed memory, executive function) and self-reported cognitive function. Linear regression models compared groups on individual cognitive domains, adjusting for age, sex, race/ethnicity, education level, and habitual sleep quality. RESULTS: Retired night shift workers scored lower than retired day workers on attention (Bâ =â -0.38, 95% CI [-0.75, -0.02], pâ =â .040) and executive function (Bâ =â -0.55, 95% CI [-0.92, -0.17], pâ =â .005). In post hoc analyses, attention and executive function were unrelated to diary-assessed habitual sleep characteristics (disruption, timing, and irregularity) in retired night shift workers. CONCLUSIONS: The observed cognitive weaknesses in retired night shift workers may suggest increased risk for future dementia. Retired night shift workers should be followed to determine whether observed weaknesses progress.
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Demencia , Trastornos del Sueño del Ritmo Circadiano , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Jubilación , Sueño , Cognición , Tolerancia al Trabajo Programado/psicología , Ritmo CircadianoRESUMEN
Abstract. BACKGROUND: Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics. METHODS: Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report. RESULTS: After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed. CONCLUSIONS: There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.
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Significance: Functional near-infrared spectroscopy (fNIRS) is a noninvasive technology that uses low levels of nonionizing light in the range of red and near-infrared to record changes in the optical absorption and scattering of the underlying tissue that can be used to infer blood flow and oxygen changes during brain activity. The challenges and difficulties of reconstructing spatial images of hemoglobin changes from fNIRS data are mainly caused by the illposed nature of the optical inverse model. Aim: We describe a Bayesian approach combining several lasso-based regularizations to apply anatomy-prior information to solving the inverse model. Approach: We built a Bayesian hierarchical model to solve the Bayesian adaptive fused sparse overlapping group lasso (Ba-FSOGL) model. The method is evaluated and validated using simulation and experimental datasets. Results: We apply this approach to the simulation and experimental datasets to reconstruct a known brain activity. The reconstructed images and statistical plots are shown. Conclusion: We discuss the adaptation of this method to fNIRS data and demonstrate that this approach provides accurate image reconstruction with a low false-positive rate, through numerical simulations and application to experimental data collected during motor and sensory tasks.
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OBJECTIVE: To examine which 24-hour rest-activity rhythm (RAR) characteristics are associated with depression symptoms in stroke survivors. DESIGN: Cross-sectional observational study examining associations of RAR characteristics with the presence of depression symptoms adjusting for age, sex, race, and medical comorbidity. SETTING: Community setting. PARTICIPANTS: Stroke survivors: (1) recruited locally (N women=35, N men=28) and (2) a nationally representative probability sample (the National Health and Nutrition Examination Survey [NHANES]; N women=156, N men=124). INTERVENTIONS: None. MEASUREMENTS: Objective RAR characteristics derived from accelerometer recordings including activity onset/offset times and non-parametric measures of RAR strength (relative amplitude), stability (interdaily stability), and fragmentation (intradaily variability). The presence of depression symptoms was categorized using Patient Health Questionnaire scores. RESULTS: In both samples, the only RAR characteristic associated with depression symptoms was intradaily variability (fragmentation): local sample, odds ratio=1.96 [95% confidence interval=1.05-3.63]; NHANES sample, odds ratio=1.34, [95% confidence interval=1.01-1.78]). In the NHANES sample, which included both mild and moderate/severe depression, the association between 24-hour sleep-wake fragmentation and depression symptoms was driven by moderate-to-severe cases. CONCLUSIONS: Stroke survivors with higher levels of RAR fragmentation were more likely to have depression symptoms in both samples. These findings have implications, given prior studies in general samples linking RAR fragmentation with future depression and dementia risk. Research is needed to establish the potential consequences, mechanisms, and modifiability of RAR fragmentation in stroke survivors.
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Sueño , Accidente Cerebrovascular , Masculino , Humanos , Femenino , Encuestas Nutricionales , Ritmo Circadiano , Depresión/epidemiología , Estudios Transversales , Actigrafía , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND: Despite the high prevalence of depression and disruption to 24-h sleep-wake routines following the death of a spouse in late-life, no bereavement interventions have been developed to re-entrain a regular sleep-wake routine among older widow(er)s. We describe the rationale and methodology of the NIH-funded WELL Study (Widowed Elders' Lifestyle after Loss), a randomized controlled trial (RCT) comparing the efficacy of a digital health intervention (DHI) to enhanced usual care (EUC) arm for reducing depression symptoms in older spousally-bereaved adults. METHODS: We will randomize approximately 200 recently bereaved (<12 months) adults aged 60+ years to one of two 12-week interventions: digital monitoring of the timing and regularity of sleep, meals, and physical activity plus weekly motivational health coaching; or enhanced usual care consisting of weekly telephone calls and similar assessment schedules. Participants will complete self-report and clinical assessments at baseline, post-intervention, and 3-, 6-, and 12-months post-intervention, and objective actigraphic assessments of their 24-h rest-activity rhythm (RAR) at baseline and 1-, 2-, and 3-months during the intervention. The primary outcome is change in depression symptoms burden (using the Hamilton Rating Scale for Depression) from pre- to post-intervention and over 12 months of follow-up. DISCUSSION: WELL Study findings will inform the development of widely generalizable and scalable technology-based interventions to support bereaved spouses in community-based settings. Clinical http://Trials.gov Identifier: NCT04016896.
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Depresión , Esposos , Adulto , Humanos , Anciano , Depresión/prevención & control , Sueño , Ejercicio Físico , Comidas , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale-Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later. RESULTS: Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen's d ≤ -0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit ß = -0.8, 95% confidence interval: -1.6, -0.1, p = 0.03) independent of self-reported activity restriction and other key factors. CONCLUSIONS: These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).
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Demencia , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Femenino , Anciano , Masculino , Cuidadores , Depresión/diagnósticoRESUMEN
BACKGROUND: Consistent evidence from retrospective reports and case registry studies indicates that a history of depression is a major risk factor for depression in the peripartum period. However, longitudinal studies with racially and socioeconomically diverse samples of young mothers are lacking, and little is known about developmental patterns of depression across the lifespan that can inform preventive interventions. METHODS: Young primiparous mothers (n = 399, 13-25 years, 81% Black) were recruited from a population-based prospective study that began in childhood. Women reported on depression symptoms for at least 3 years prior to their pregnancy, during pregnancy, and at 4 months postpartum. Linear regression models were used to estimate change in pre-pregnancy depression severity and to evaluate associations between patterns of lifetime history and postpartum depression symptoms. RESULTS: Results revealed high levels of continuity in depression from pregnancy to postpartum, and across multiple years pre-pregnancy to postpartum. Overall, depression severity leading up to pregnancy decreased over time, but patterns of worsening or improving symptoms were not associated with depression severity in the postpartum period. Instead, area under the pre-pregnancy trajectory curve, representing cumulative lifetime depression burden, was uniquely associated with postpartum depression after adjusting for prenatal depression severity. CONCLUSIONS: Depression in the postpartum period should be considered within a lifespan perspective of risk that accumulates before conception. Clinical screening and early interventions are needed in adolescence and young adulthood to prevent the onset and persistence of depressive symptoms that could have long-term implications for peripartum health.
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Depresión Posparto , Embarazo , Adolescente , Femenino , Humanos , Adulto Joven , Adulto , Depresión Posparto/epidemiología , Depresión Posparto/diagnóstico , Madres , Depresión/epidemiología , Depresión/diagnóstico , Estudios Retrospectivos , Longevidad , Estudios Prospectivos , Periodo PospartoRESUMEN
Many studies collect functional data from multiple subjects that have both multilevel and multivariate structures. An example of such data comes from popular neuroscience experiments where participants' brain activity is recorded using modalities such as electroencephalography and summarized as power within multiple time-varying frequency bands within multiple electrodes, or brain regions. Summarizing the joint variation across multiple frequency bands for both whole-brain variability between subjects, as well as location-variation within subjects, can help to explain neural reactions to stimuli. This article introduces a novel approach to conducting interpretable principal components analysis on multilevel multivariate functional data that decomposes total variation into subject-level and replicate-within-subject-level (i.e., electrode-level) variation and provides interpretable components that can be both sparse among variates (e.g., frequency bands) and have localized support over time within each frequency band. Smoothness is achieved through a roughness penalty, while sparsity and localization of components are achieved by solving an innovative rank-one based convex optimization problem with block Frobenius and matrix $L_1$-norm-based penalties. The method is used to analyze data from a study to better understand reactions to emotional information in individuals with histories of trauma and the symptom of dissociation, revealing new neurophysiological insights into how subject- and electrode-level brain activity are associated with these phenomena. Supplementary materials for this article are available online.