The overall purpose of this study is to understand the role of disrupted sleep in the association of exposure to early life adversity (adverse childhood experiences (ACEs)) with vascular endothelial (dys)function.
In Aim 1 (The Iowa ACEs and Sleep Cohort Study), the investigators will utilize a cross-sectional cohort design with a state-of-the-art translational approach. Participants will be recruited to objectively characterize the degree to which lower sleep quality and quantity contribute to ACEs-related endothelial dysfunction, inflammation, and oxidative stress in young adults using:
1. rigorous at home sleep monitoring using 7-nights of wrist actigraphy and 2 nights of home-based polysomnography to objectively measure sleep quality (sleep efficiency, wakefulness after sleep onset and sleep depth), and total sleep duration, 2. in vivo assessment of endothelial function via flow-mediated dilation testing, and 3. in vitro determination of endothelial cell inflammation and oxidative stress from biopsied endothelial cells. This study to achieve this Aim.
In Aim 2, approximately 70 eligible participants from Aim 1 (The Iowa ACEs and Sleep Cohort Study) will then be randomized to either a 6-week behavioral sleep intervention (cognitive behavioral therapy for insomnia) or a wait-list control to determine the mechanistic contribution of sleep disruption to vascular dysfunction in young adults with moderate-to-high exposure to adverse childhood experiences (ACEs). Following the intervention, participants will again complete:
1. rigorous at home sleep monitoring using 7-nights of wrist actigraphy and 2 nights of home-based polysomnography to objectively measure sleep quality (sleep efficiency, wakefulness after sleep onset and sleep depth), and total sleep duration, 2. in vivo assessment of endothelial function via flow-mediated dilation testing, and 3. in vitro determination of endothelial cell inflammation and oxidative stress from biopsied endothelial cells.
18-29 years of age
SBP <129 and DBP <90 mmHg
Body Mass Index > 18.5 kg/m2 and <35 kg/m2
Willing to complete in-home sleep studies
Currently undergoing treatment for a sleep disorder or diagnosed with restless leg syndrome, hypersomnia, parasomnia or narcolepsy, or obstructive sleep apnea
Currently performing overnight shift work
Lifetime history of any psychiatric disorder with psychotic features or bipolar disorder, currently undergoing treatment for substance-induced mood disorder
Endorsed suicidal ideation as indicated by a Moderate or High risk determination on the Columbia Suicide Risk Protocol
Parallel
Cognitive Behavioral Therapy for Insomnia (CBT-i)
BehavioralCBT-I is a structured program with a robust empirical evidence supporting its efficacy for improving sleep quality and quantity. The cognitive component of CBT-I teaching individuals how to recognize and change the beliefs they hold about sleep that negatively impact sleep, such as negative thoughts and emotions. The behavioral component includes several strategies to help improve sleep, including: improved sleep hygiene, improving the sleep environment, relaxation training, stimulus control therapy (consistent wake/sleep times, using the bed only for sleep, etc), and sleep restriction. Sleep restriction consists of reducing the time spend in bed initially to increase sleep drive in subsequent nights. Once sleep has improved, the time in bed is gradually increased again.
Vascular Endothelial Function
The brachial artery flow-mediated dilation (FMD) technique, a non-invasive bioassay of endothelium-dependent vasodilatory function, will be used as the primary determinant of in-vivo vascular endothelial function.
Endothelial NFκB p65 expression.
Vascular endothelial cells will be biopsied and stained for inflammatory marker NFκB p65.
Endothelial TNF-α expression.
Vascular endothelial cells will be biopsied and stained for inflammatory marker TNF-α.
Endothelial MCP-1 expression.
Vascular endothelial cells will be biopsied and stained for inflammatory marker MCP-1.
Endothelial NADPH-oxidase p47phox expression.
Vascular endothelial cells will be biopsied and stained for NADPH-oxidase p47phox, a marker of oxidative stress.
Sleep Quality
The investigators will objectively quantify sleep quality as actigraphy measured as sleep efficiency (PRIMARY independent variable) and wakefulness after sleep onset and PSG measured sleep depth as indicated by the relative time spent in slow wave sleep. The investigators will also assess sleep efficiency and wakefulness after sleep onset using sleep diaries. These parameters are considered the independent variable in this study, with the primary identified independent variable identified as sleep efficiency. Collection of these data will be used to a) confirm changes and b) examine whether changes in the variables do in fact mediate changes in vascular function.
Sleep Duration
The investigators will objectively quantify total sleep duration using actigraphy and via sleep diary.
Anxiety and Depression
Anxiety and depression symptoms will be assessed using the "Inventory of Depression and Anxiety Symptoms-II" (IDAS-II), which is a reliable, well-validated assessment of mood and anxiety disorder symptoms. Using this scale, anxiety and depression ill be well-measured, and the investigators will assess their role as confounders/mediators in analyses. Each scale is individually assessed, meaning that the minimum score for mood symptoms, specifically, ranges from 3-20, and the maximum score ranges from 15-100 for this scale. With regards to anxiety disorder symptoms, the minimum score ranges from 3-8, and the maximum score ranges from 15-40. Higher scores on scales indicate worse outcomes.
Trauma
Trauma symptoms will be assessed using the "PTSD Checklist for DSM-5" (PCL-5) with Life Events checklist. Using this scale, trauma symptoms will be well-measured, and the investigators will assess their role as confounders/mediators in analyses. The minimum value for this scale is "0" and the maximum value for this scale is "80". Higher scores on this scale indicate a worse outcome.
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Nathaniel Jenkins
Lead sponsor
University of Iowa
Sponsor institution
