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

NCT04424407 | Completed Results DMC

• 2 other identifiers: IRB-56961R61MH120245
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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-amygdala 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.

Conditions

Insomnia; Depression

Keywords

Insomnia; Depression; Anxiety; CBT-I; Cognitive Behavioral Therapy for Insomnia

Outcome Measures

Primary Outcomes (6)

• Change in Amygdala Activation During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging

  The Conscious condition of the Facial Expressions of Emotion task measures supraliminal (without backward masking) emotional face processing. Amygdala activation while viewing threat-related emotional faces relative to neutral faces was quantified using functional magnetic resonance imaging (fMRI) as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional faces using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to emotional faces, relative to neutral faces. A negative value for the change in amygdala activation means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes.

  Assessed at week 0 and week 11

• Change in Amygdala Activation During the Facial Expressions of Emotion Task (Nonconscious Condition) as Assessed by Functional Magnetic Resonance Imaging

  The Nonconscious condition of the Facial Expressions of Emotion task measures subliminal (with backward masking) emotional face processing. Amygdala activation while viewing threat-related emotional faces relative to neutral faces was quantified using fMRI as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional faces using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to emotional faces, relative to neutral faces. A negative value for the change in amygdala activation means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes.

  Assessed at week 0 and week 11

• Change in Amygdala Activation During the Emotion Regulation Scenes Task

  Participants are asked to "look" or "decrease" their emotional response to negative and neutral valence images taken from the International Affective Picture System. Amygdala activation while viewing emotional scenes relative to neutral scenes, and while passively viewing emotional scenes relative to down-regulating emotion, was quantified using fMRI as a marker of Emotion Regulation Network engagement. Blood-oxygenation level dependent (BOLD) signal change before and after CBT-I treatment was compared by modeling the activity of the amygdala while viewing emotional scenes or while downregulating using generalized linear models, producing beta weights for each participant and timepoint. A positive beta-weight at pre-treatment means that the amygdala increased its activity in response to the task demands, and a negative value means that average amygdala reactivity decreased following treatment. It is theorized that higher amygdala emotional reactivity is associated with worse outcomes

  Assessed at week 0 and week 11

• Change in Amygdala-Medial Prefrontal Cortex Connectivity During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging

  This outcome tested whether amygdala connectivity with regions of the mPFC was changed following treatment using psychophysiological interaction (PPI) analysis for this contrast/task. Regions of the mPFC include: dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), dorsomedial prefrontal cortex (dmPFC), subgenual anterior cingulate cortex (sgACC), pregenual anterior cingulate cortex (pACC). PPI analyses produce a beta weight for each participant at each timepoint, and represents the degree to which the connectivity of the amygdala and mPFC is modulated by task conditions. A positive value means average connectivity increases in the task-contrast, and a positive value for the change score means an increase in average connectivity following CBT-I treatment. It is theorized that higher amygdala connectivity is associated with better outcomes.

  Assessed at week 0 and week 11

• Change in Beck Depression Inventory (BDI)

  This measure is of the Beck Depression Inventory-II total score after excluding one sleep item. 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 summed to create an overall score of 0 to 63. higher scores indicate greater levels of severity. The ranges for depression are: 0-13 minimal, 14-19 mild, 20-28 moderate, and 29-63 severe. A negative change score means that average depression symptom severity was reduced following CBT-I treatment.

  Assessed at week 0 and week 11

• Change in PSG Sleep Efficiency

  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. A positive change score means average sleep efficiency increased following CBT-I treatment.

  Assessed at week 0 and week 11

Secondary Outcomes (16)

• Change in Beck Scale of Suicidal Ideation Total Score

  Assessed at week 0 and week 11

• Change in Columbia Suicide Severity Rating Scale

  Assessed at week 0 and week 11

• Change in Actigraph Sleep Onset Latency (SOL) as a Measure of Sleep Continuity

  Assessed at week 0 and week 11

• Change in Actigraph Number of Arousals as a Measure of Sleep Continuity

  Assessed at week 0 and week 11

• Change in Actigraph Wake After Sleep Onset (WASO) as a Measure of Sleep Continuity

  Assessed at week 0 and week 11

Study Arms (1)

CBT-I

OTHER

Behavioral: Cognitive Behavioral Therapy for Insomnia

Interventions

Cognitive Behavioral Therapy for Insomnia BEHAVIORAL

Participants will meet with a psychologist once a week for six weeks to complete a brief CBT-I intervention. Cognitive Behavioral Therapy for Insomnia consists of a cognitive therapy and a behavioral therapy. The cognitive therapy is designed to identify incorrect ideas about sleep, challenge their validity, and replace them with correct information. This therapy tries to reduce worry, anxiety, and fear that one won't sleep by providing accurate information about sleep. The behavioral therapy increases sleep quality by limiting excessive time spent in bed to increase homeostatic sleep drive and sleep consolidation.

Also known as: CBT-I

CBT-I

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Individuals who are not CPAP adherent or have untreated OSA of moderate severity or worse (AHI ≥ 15)

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Depression; Anxiety Disorders

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Andrea Goldstein-Piekarski, PhD
• Organization: Stanford University

agoldpie@stanford.edu

650-721-4780

Study Officials

• Andrea Goldstein-Piekarski, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This is a single-armed trial. All participants will receive Cognitive Behavioral Therapy for Insomnia

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 11, 2020
• Study Start: May 28, 2021
• Primary Completion: March 23, 2024
• Study Completion: March 23, 2024
• Last Updated: October 15, 2025
• Results First Posted: October 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)