Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Sleep Deprivation

NCT05893173 | Completed

• 1 other identifier: 853162
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

In the treatment of Major Depressive Disorder (MDD), total sleep deprivation can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as sleep deprivation has been suggested to increase synaptic strength. Although determining how sleep deprivation impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of sleep deprivation. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity, in addition to using a proxy measure, waking EEG theta activity, to assess synaptic strength following total sleep deprivation. Ten individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging and waking EEG prior to and following approximately 30 hours of total sleep deprivation. Both clinician-administered and subjective mood measures will be collected. It is predicted that sleep deprivation will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• GluCEST imaging metrics

  relative change in glutamate concentration (% baseline)

  after 24 hours of sleep deprivation

Study Arms (1)

Major Depressive Disorder

Ten individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging and waking EEG prior to and following approximately 30 hours of total sleep deprivation.

Behavioral: Sleep Deprivation

Interventions

Sleep Deprivation BEHAVIORAL

Ten individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following approximately 30 hours of total sleep deprivation.

Major Depressive Disorder

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This pilot study is targeting N=10 subjects (10 depressed patients). We will recruit outpatients with current depression from the Philadelphia and University of Pennsylvania community.

You may qualify if:

• Age between 18 and 85 years; Current depression as assessed on the SCID;
• Stable, normally-timed sleep-wake cycle as determined by interview, 1 week daily sleep log, and defined by:
• Habitual nocturnal sleep duration between 6h and 9h.
• Habitual morning awakening between 0600h and 0800h. Able to comprehend English, as all questionnaires are in this language Ability to provide informed consent

You may not qualify if:

• Shift work, transmeridian travel or irregular sleep/wake routine in past 60 days; A sleep disorder other than insomnia, as determined by history or actigraph; History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders as assessed on the SCID; Previous electroconvulsive therapy in the past 6 months; Alcohol or drug abuse in the past year based upon the SCID or urine toxicology screen; A current smoker; Any significant medical or neurological illness that impacts brain function or impedes participation; History of head trauma with significant loss of consciousness; Metallic implants, pacemakers or tattoos, or other contraindications to MRI; Claustrophobic, or intolerant of the scanner environment; Visual or auditory impairment severe enough to compromise task performance as judged by the PI; For women, pregnancy will exclude participation.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2023
• First Posted: June 7, 2023
• Study Start: June 19, 2023
• Primary Completion: February 2, 2025
• Study Completion: February 2, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)