Neuroimaging Sleep and Mood in Depression

Study Overview
=================
Brief Summary
-----------------
This study will investigate how sleep and mood are related in patients with depression and in healthy controls. It will use MRI-based measures of brain function to determine how neural systems are modulated by sleep and sleep deprivation, and its links to mood in depression.

Detailed Description
-----------------
The purpose of this work is to identify brain networks that underlie sleep and mood using a combination of EEG and fMRI. Sleep deprivation can elicit rapid improvements in mood in some patients with depression, while some patients do not show any significant changes in mood. We will image the brain while measuring physiological and electrical signals in healthy individuals and in patients with depression. Subjects will participate in combined EEG-MRI studies that will involve the use of perceptual and attentional tasks, and will involve recording physiological variables such as breathing, heart rate, eye movements, and blood pressure. If combined EEG-MRI cannot be completed due to data quality reasons, subjects will participate in EEG or MRI alone. Subjects will participate in a blood draw to assess for inflammatory markers related to mood. Subjects will be either well-rested or sleep deprived. For sleep deprivation, subjects will be asked to stay awake overnight under the supervision of a member of the study team at Boston University, and then would be asked to do an fMRI, EEG, or EEG-MRI scan. fMRI studies will be performed at the Boston University Center for Cognitive Neuroimaging. During the study visit, subjects will answer questions in structured interviews, will fill out questionnaires that will contain questions related to their mental health. Subjects will be shown visual stimuli and/or listen to auditory stimuli, and/or asked to perform simple behavioral tasks related to these stimuli. Some of the visual stimuli will be emotionally salient. Wrist actigraphy will be used to monitor sleep behavior. Remote daily mood and sleep assessments will be performed for up to two weeks prior to imaging. These assessments will be sent as emails or text messages to participants.

Official Title
-----------------
Identifying Brain Dynamics Underlying Sleep and Mood in Depression

Conditions
-----------------
Major Depression

Intervention / Treatment
-----------------
* Behavioral: Sleep deprivation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Adult aged 18-80 Inclusion criteria for patient cohort only: - Current diagnosis of major depressive disorder Exclusion criteria: Must not have ferrous metal implanted in head or body Must have no history of major head trauma Must not have implanted electronic devices (e.g., pacemaker, neurostimulator) Must not be pregnant, suspect they are pregnant, or seeking to become pregnant Must not be claustrophobic Must have no piercings or jewelry that cannot be removed Weight less than 250 pounds No lifetime history of schizophrenia or any other psychosis disorder, substantial intellectual disability, bipolar disorder, post-traumatic stress disorder or obsessive compulsive disorder No alcohol or substance abuse or dependence within the past 6 months No significant personality dysfunction Must not indicate significant suicide risk. Must not be taking medications that significantly affect sleep, psychiatric function, blood/vascular function, or anti-inflammatory medications (other than minor NSAID use).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Two groups (healthy vs major depression) are studied under two conditions (rested vs sleep deprivation).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep deprived<br>Overnight sleep deprivation | Behavioral: Sleep deprivation<br>* Overnight sleep deprivation.<br>|
| No Intervention: Rested<br>Well-rested sleep pattern | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fMRI signals in thalamus region of interest (ROI) from baseline to post intervention | fMRI signal (units: %) | Through study completion (approximately 1 month) | 
| Change in fMRI signals in amygdala ROI from baseline to post intervention | fMRI signal (units: %) | Through study completion (approximately 1 month) | 
| Change in tasked evoked responses in amygdala ROI from baseline to post intervention | Task evoked responses in amygdala ROI (units: %) | Through study completion (approximately 1 month) | 
| Change in cerebrospinal fluid (CSF) flow measurements from baseline to post intervention | Fluid flow measured with MRI (units: %) | Through study completion (approximately 1 month) | 
| Change in Montgomery-Asberg Depression Rating from baseline to post intervention | Mood scores, measured on scale of 0-60 | Through study completion (approximately 1 month) | 
| Change in whole-brain voxelwise fMRI activity from baseline to post intervention | fMRI measure of hemodynamics (units: %) | Through study completion (approximately 1 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in EEG dynamics from baseline to post intervention | Amplitude of EEG signals (units: uV^2) | Through study completion (approximately 1 month) | 
| Change in dot probe task performance from baseline to post intervention | Behavior on emotional task (units: ms) | Through study completion (approximately 1 month) | 
| Change in blood biomarkers of C-reactive protein from baseline to post intervention | Blood analysis results (units: mg/L) | Through study completion (approximately 1 month) | 
| Change in blood levels of Interleukin 6 from baseline to post intervention | Measured in pg/mL | Through study completion (approximately 1 month) | 
| Change in Magnetic Resonance Spectroscopy (MRS) measurement of lactate from baseline to post intervention | MRS measure of lactate (units: i.u.) | Through study completion (approximately 1 month) | 
| Change in MRS measurement of myo-inositol from baseline to post intervention | Magnetic Resonance Spectroscopy measure of myo-inositol (units: i.u.) | Through study completion (approximately 1 month) | 
| Change in Positive and Negative Affect Scale 21 (PANAS-21) rating from baseline to post intervention | The Positive and Negative Affect Scale (PANAS-21) assess positive and negative affect using scales relating to how participants feel about certain words. | Through study completion (approximately 1 month) | 
| Change in Positive and Negative Affect Scale 21 (PANAS-21) rating during intervention | The Positive and Negative Affect Scale (PANAS-21) assess positive and negative affect using scales relating to how participants feel about certain words. | Throughout intervention (approximately 17 hours) | 
| Change in Shame Inventory rating from baseline to post intervention | The Shame Inventory assess participants' feelings related to shame. Units: scale. | Through study completion (approximately 1 month) | 
| Change in Shame Inventory rating during intervention | The Shame Inventory assess participants' feelings related to shame. Units: scale. | Throughout intervention (approximately 17 hours) | 
| Change in Anxiety Sensitivity Index (ASI-3) rating from baseline to post intervention | The Anxiety Sensitivity Index assess participants' concern related to anxiety.Units: scale. | Through study completion (approximately 1 month) | 
| Change in Anxiety Sensitivity Index (ASI-3) rating during intervention | The Anxiety Sensitivity Index assess participants' concern related to anxiety.Units: scale. | Throughout intervention (approximately 17 hours) | 
| Change in Depression, Anxiety, and Stress Scale (DASS-21) rating from baseline to post intervention | The Depression, Anxiety, and Stress Scale assesses participants emotional states. Units: scale. | Through study completion (approximately 1 month) | 
| Change in Depression, Anxiety, and Stress Scale (DASS-21) rating during intervention | The Depression, Anxiety, and Stress Scale assesses participants emotional states. Units: scale. | Throughout intervention (approximately 17 hours) | 
| Patient health questionnaire (PHQ-9) | This patient health questionnaire is used to compute a general depression score.Units: scale. | Pre-enrollment |