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.

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Key information

Conditions

Depression, Unipolar Depressive Disorder Mental Disorders Mood Disorders

Age range

21 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sleep deprivation

Behavioral

36-hours total sleep deprivation

Primary outcomes

Change in HAMD-NOW scores

Time frame: Each morning for 4 days

Total score on a modified Hamilton Depression Inventory that assesses mood symptoms in the moment.

Secondary outcomes

Change in neuroimaging

Time frame: Each morning for 3 days

Resting-state brain functional connectivity on fMRI

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Registry information

Important dates

Study start: 2016
Primary completion: 2020
Study completion: 2020
First posted: May 30, 2017
Registry last updated: Mar 25, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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