A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety

Not Applicable

Completed

• Conditions: Depression; Insomnia
• Interventions: Behavioral: Cognitive Behavioral Therapy for Insomnia

• Registration Number: NCT04424407
• Lead Sponsor: Stanford University

Brief Summary

Several lines of evidence suggest that unhealthy sleep patterns contribute to depressive symptoms through disruption of brain networks that regulate emotional functions. However, we do not yet know to what degree the emotion regulation brain network is modified by the restoration of sleep, or whether the degree to which a sleep intervention modifies these neural targets mediates reductions in other depressive symptoms including suicidality.

The overall aim is to test the efficacy of an established sleep intervention (Cognitive Behavioral Therapy for Insomnia (CBT-I)) in reducing depressive symptoms through improving emotion regulation brain function in individuals with elevated depressive symptoms and clinically meaningful sleep disturbance.

In this study, we will assess feasibility of recruitment and retention as well as target engagement. Target engagement is defined as the treatment effect on increasing mPFC-amydgala connectivity, and/or decreasing amygdala reactivity during emotion reactivity and regulation paradigms. Participants will be 70 adults experiencing at least moderate sleep disturbances and who also have elevated anxious and/or depressive symptoms. Emotion distress and sleep disruption will be assessed prior to, and weekly while receiving six Cognitive Behavioral Therapy for Insomnia (CBT-I) across a period of 8 weeks. CBT-I improves sleep patterns through a combination of sleep restriction, stimulus control, mindfulness training, cognitive therapy targeting dysfunctional beliefs about sleep, and sleep hygiene education. Using fMRI scanning, emotion regulation network neural targets will be assayed prior to and following completion of CBT-I treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-03
• Study First Submitted QC: 2020-06-05
• Study First Posted: 2020-06-11
• Study Start: 2021-05-28
• Primary Completion: 2024-03-23
• Study Completion: 2024-03-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-21
• Last Update Posted: 2024-11-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

• Ages 25-60
• Subjective complaint of sleep disturbance for ≥ 3 months (ISI≥10)
• Subjective complaint of depression (BDI≥14) and not at imminent risk for suicide, as measured by CSSRS assessment
• Fluent and literate in English
• Written informed consent.
• Reside within 60 miles of Stanford University

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Exclusion Criteria

• Presence of other sleep or circadian rhythm disorders
• Medications that would significantly impact sleep, alertness, or mood
• >14 alcoholic drinks per week or >4 drinks per occasion
• General medical condition, disease or neurological disorder that interferes with the assessments or outpatient participation
• Substance abuse or dependence
• Mild traumatic brain injury
• Severe impediment to vision, hearing and/or hand movement, likely to interfere with the ability to follow study protocols
• Pregnant or breast feeding
• Current or lifetime history of bipolar disorder or psychosis
• Current or or expected cognitive behavior therapy or other evidence-based psychotherapies for another condition
• Received CBT-I within the past year
• Acute or unstable chronic illness
• Current exposure to trauma, or exposure to trauma within the past 3 months
• Working a rotating shift that overlaps with 2400h.
• Presence of suicidal ideations representing imminent risk as determined by the empirically-supported, standardized suicide risk assessment" to the exclusion criteria
• Individuals who are not CPAP adherent or have untreated OSA of moderate severity or worse (AHI ≥ 15)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CBT-I	Cognitive Behavioral Therapy for Insomnia	-

Primary Outcome Measures

Name	Time	Method
Change in Emotion Regulation Network brain activation as assessed by functional magnetic resonance imaging	Assessed at week 0 and week 11	During functional magnetic resonance imaging the Emotion Regulation Network will be engaged by emotional tasks, and circuit activation will be quantified by blood flow in regions of interest.
Change in Beck Depression Inventory	Assessed at week 0 and week 11	This measure is of the Beck Depression Inventory-II total score after excluding one sleep item. The average item score for the remaining 20 items will be multiplied by 21 (the original number of items), to create a modified depression scale that maintains the original range (ranges: 0-13 minimal, 14-19 mild, 20-28 moderate, and 29-63 severe).; The BDI-II is a 21-item self-report scale with high validity and reliability that assesses the severity of depression symptoms. The depression items consist of: sadness, pessimism, past failure, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, irritability, changes in appetite, concentration difficulty, tiredness or fatigue, and loss of interest in sex. Items are scored from 0 to 3, and higher scores indicate greater levels of severity.
Change in Emotion Regulation Network brain connectivity as assessed by functional magnetic resonance imaging	Assessed at week 0 and week 11	During functional magnetic resonance imaging the Emotion Regulation Network will be engaged by emotional tasks, and circuit connectivity will be quantified by the correlation of the blood flow between regions of interest.
Change in PSG Sleep Efficiency	Assessed at week 0 and week 11	Sleep efficiency (SE) is the percentage of total time in bed actually spent sleeping. Based on the overnight PSG sleep recording, SE will be calculated as the total time (minutes) spent asleep (sum of Stages N1, N2, N3, and REM) divided by the total time (minutes) in bed, and multiplied by 100.

Secondary Outcome Measures

Name	Time	Method
Change in Actigraph Sleep Onset Latency (SOL) as a Measure of Sleep Continuity	Assessed at week 0 and week 11	Sleep Onset Latency (SOL) is the time (minutes) from "lights out" to actually falling asleep (sleep onset).
Change in Actigraph Number of Arousals as a Measure of Sleep Continuity	Assessed at week 0 and week 11	Number of Arousals is determined by number of times of awakening as seen on the actigraph data.
Change in PSG Sleep Efficiency (SE) as a Measure of Sleep Architecture	Assessed at week 0 and week 11	Sleep Efficiency (SE) is calculated as TST divided by total time spent in bed, multiplied by 100.; Duration of non-rapid eye movement (NREM) sleep includes stages N1, N2, and N3, and is measured in minutes. The duration of sleep outside of those stages that is associated with specific EEG stages is REM sleep.
Change in Actigraph Total Sleep Time (TST) as a Measure of Sleep Continuity	Assessed at week 0 and week 11	Total Sleep Time (TST) is the total time spent asleep, from the start of sleep onset to sleep offset subtracting any periods of wakefulness.
Change in 36-Item Short Form Survey (SF-36) Score	Assessed at week 0 and week 11	The SF-36 measures health-related quality of life based on eight domains: limitations in physical activities because of health problems, limitations in social activities because of physical or emotional problems, limitations in usual role activities because of physical health problems, bodily pain, general mental health (psychological distress and well-being), limitations in usual role activities because of emotional problems, vitality (energy and fatigue), and general health perceptions. Items are recoded then averaged together to create each scale. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered.
Change in Beck Anxiety Inventory	Assessed at week 0 and week 11	The BAI is a 21-item self-report scale that assesses the severity of anxiety symptoms.; Items are scored from 0 to 3 (0 = not at all, 3 = severe). Higher scores indicate greater levels of severity, and the ranges for anxiety levels are: 0-9 normal to minimal, 10-18 mild to moderate, 19-29 moderate to severe, and 30-63 severe. The BAI consists of two factors: somatic and cognitive.
Change in Columbia Suicide Severity Rating Scale	Assessed at week 0 and week 11	The Columbia Suicide Severity Rating Scale is a 12-item checklist that was designed to quantify the severity of suicidal ideation and behavior. It is composed of two parts. The first six questions ask about suicidal ideation and behavior in the past month while the last six questions ask about suicidal ideation and behavior since the last visit. The CSSRS has been proven to be reliable and valid. It has also been shown to have high sensitivity and specificity to the different suicidal behavior classifications.
Change in Actigraph Wake After Sleep Onset (WASO) as a Measure of Sleep Continuity	Assessed at week 0 and week 11	Wake After Sleep Onset (WASO) are periods of wakefulness occurring after sleep onset, before final awakening (sleep offset).
Change in Actigraph Sleep Efficiency (SE) as a Measure of Sleep Continuity	Assessed at week 0 and week 11	Sleep Efficiency (SE) is calculated as TST divided by total time spent in bed, multiplied by 100.
Change in PSG Sleep Onset Latency (SOL) as a Measure of Sleep Architecture	Assessed at week 0 and week 11	Sleep Onset Latency (SOL) is the time (minutes) from "lights out" or start of total recording time, to actually falling asleep as indicated by EEG changes.
Change in PSG Number of Arousals as a Measure of Sleep Architecture	Assessed at week 0 and week 11	Number of Arousals is determined by number of times of awakening by EEG changes.
Change in PSG Wake After Sleep Onset (WASO) as a Measure of Sleep Architecture	Assessed at week 0 and week 11	Wake After Sleep Onset (WASO) are periods of wakefulness occurring after sleep onset, before final awakening (sleep offset) measured by EEG changes.
Change in PSG Total Sleep Time (TST) as a Measure of Sleep Architecture	Assessed at week 0 and week 11	Total Sleep Time (TST) is the total time (minutes) spent asleep, from the start of sleep onset to sleep offset, subtracting any periods of wakefulness. TST includes stages N1, N2, N3, and REM sleep.
Change in Respiratory Sinus Arrhythmia (RSA)- measured by PSG	Assessed at week 0 and week 11	RSA is the phenomenon of an increased heart rate during inhalation and a decreased heart rate during exhalation. Since these fluctuations are controlled mainly by vagal influences on the heart, RSA serves as a reliable metric for measuring parasympathetic activity. RSA has been proven to be a reliable measure of emotion regulation and emotional responding in numerous studies.
Change in Sleep Physiology measured by PSG	Assessed at week 0 and week 11	Topographical EEG power spectral density analysis associated with sleep stages will be calculated in the Delta (0.5-Hz), Theta (4-7Hz), Alpha (7-11Hz), Sigma (12-15Hz), Beta-1 (15-20Hz), Beta-2 (20-35Hz) and Gamma (35-45Hz) bands, according to published methods.
Change in Insomnia Severity Index (ISI) Scale Score	Assessed at week 0 and week 11	Subjective ratings of sleep disturbance and insomnia severity will be assessed with the Insomnia Severity Index. The Insomnia Severity Index (ISI) is a 7-item self-report measure of insomnia type, severity, and impact on functioning. The items consist of severity of sleep onset, sleep maintenance, early morning awakenings, sleep dissatisfaction, interference with daytime functioning, noticeability of sleep problems by others, and distress caused by sleep difficulties. Items are scored from 0 to 4 (0 = no problem, 4 = very severe problem). Score ranges of insomnia are: 0-7 absent, 8-14 sub-threshold, 15-21 moderate, and 22-28 severe. The ISI has good validity and reliability.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Palo Alto, California, United States