Neural Mechanisms Underlying the Antidepressant Effects of Sleep Deprivation

From 40 to 60% of patients with depression experience a rapid and significant improvement of mood with one night of sleep deprivation (SD). The neural mechanisms underlying this effect have not been elucidated. Recent advances in functional neuroimaging have provided new opportunities to investigate state changes in regional brain function, along with a better understanding of the neural networks affected by depression and SD. Here we propose to study a group of N=48 antidepressant-free male and female patients with current depression symptom and N=12 healthy controls with no history of mood disorders before and after SD to provide mechanistic insight into the neural substrates underlying the antidepressant effects of SD. We hypothesize that SD-induced concurrent functional activity and connectivity changes in multiple brain networks related to different depressive symptom dimensions including emotion regulation, attention, arousal, self-referential, and reward processing will underlie the rapid and transient antidepressant effects of SD. Using an ABA design, multimodal brain imaging along with more traditional electroencephalographic (EEG) and neurobehavioral testing data will be acquired at baseline after normal sleep, during one night of total SD, and after one night of recovery sleep using a 5-day in laboratory protocol during which subjects will be continuously monitored by trained staff.

Study Overview

• Status: Completed
• Conditions: Depression, Unipolar
• Intervention / Treatment: Behavioral: Sleep deprivation

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Current depression as assessed on the HDRS-17 (for depressed group only)
• Body mass index within 15% of normal
• Stable, normally-timed sleep-wake cycle defined by: a. Habitual nocturnal sleep duration between 6h and 9h. b. Habitual morning awakening between 0600h and 0800h.
• Able to comprehend English, as all questionnaires are in this language
• Ability to provide informed consent

Exclusion Criteria:

• Shift work, transmeridian travel or irregular sleep/wake routine in past 60 days
• A sleep disorder other than insomnia
• History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders
• No history of depression for the control group.
• Alcohol or drug abuse in the past year
• A current smoker.
• Any acute or chronic, debilitating medical conditions, epilepsy, or thyroid disease.
• Metallic implants, pacemakers or tattoos, or history of working in metal workshops.
• Claustrophobic, or intolerant of the scanner environment.
• For women, pregnancy will exclude participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sleep deprivation; 36-hours of total sleep deprivation	Behavioral: Sleep deprivation; 36-hours total sleep deprivation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HAMD-NOW scores	Total score on a modified Hamilton Depression Inventory that assesses mood symptoms in the moment.	Each morning for 4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in neuroimaging	Resting-state brain functional connectivity on fMRI	Each morning for 3 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: May 24, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Mood Disorders; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Depressive Disorder; Sleep Deprivation
• Other Study ID Numbers: 811678

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No