A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network to Treat Depression and Anxiety
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Insomnia
- Sponsor
- Stanford University
- Enrollment
- 51
- Locations
- 1
- Primary Endpoint
- Change in Amygdala Activation During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging
- Status
- Completed
- Last Updated
- 6 months ago
Overview
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.
Investigators
Andrea Goldstein-Piekarski
Assistant Professor
Stanford University
Eligibility Criteria
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
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
Outcomes
Primary Outcomes
Change in Amygdala Activation During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging
Time Frame: Assessed at week 0 and week 11
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.
Change in Amygdala Activation During the Facial Expressions of Emotion Task (Nonconscious Condition) as Assessed by Functional Magnetic Resonance Imaging
Time Frame: Assessed at week 0 and week 11
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.
Change in Amygdala Activation During the Emotion Regulation Scenes Task
Time Frame: Assessed at week 0 and week 11
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
Change in Amygdala-Medial Prefrontal Cortex Connectivity During the Facial Expressions of Emotion Task (Conscious Condition) as Assessed by Functional Magnetic Resonance Imaging
Time Frame: Assessed at week 0 and week 11
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.
Change in Beck Depression Inventory (BDI)
Time Frame: Assessed at week 0 and week 11
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.
Change in PSG Sleep Efficiency
Time Frame: 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. A positive change score means average sleep efficiency increased following CBT-I treatment.
Secondary Outcomes
- Change in PSG Sleep Onset Latency (SOL) as a Measure of Sleep Architecture(Assessed at week 0 and week 11)
- 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)
- Change in Actigraph Total Sleep Time (TST) as a Measure of Sleep Continuity(Assessed at week 0 and week 11)
- Change in Actigraph Sleep Efficiency (SE) as a Measure of Sleep Continuity(Assessed at week 0 and week 11)
- Change in PSG Number of Arousals as a Measure of Sleep Architecture(Assessed at week 0 and week 11)
- Change in PSG Wake After Sleep Onset (WASO) as a Measure of Sleep Architecture(Assessed at week 0 and week 11)
- Change in PSG Total Sleep Time (TST) as a Measure of Sleep Architecture(Assessed at week 0 and week 11)
- Change in Sleep Physiology Measured by PSG(Assessed at week 0 and week 11)
- Change in Insomnia Severity Index (ISI) Scale Score(Assessed at week 0 and week 11)
- Change in 36-Item Short Form Survey (SF-36) Score(Assessed at week 0 and week 11)
- Change in Beck Anxiety Inventory (BAI)(Assessed at week 0 and week 11)
- Change in Respiratory Sinus Arrhythmia (RSA)- Measured by PSG(Assessed at week 0 and week 11)