Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05850676 |
| Other study ID # |
853172 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2023 |
| Est. completion date |
June 30, 2025 |
Study information
| Verified date |
August 2023 |
| Source |
University of Pennsylvania |
| Contact |
Jeremie Kautzmann, MS |
| Phone |
215-746-3067 |
| Email |
Jeremie.Kautzmann[@]Pennmedicine.upenn.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Individuals who have disorders of hypersomnolence (excessive sleepiness) often report
symptoms of depression. The goal of this study is to further understand of the relationship
between depression and hypersomnia by examining mood-relevant domains of slow wave sleep and
reward function.
Description:
There are often challenges in the diagnosis of Idiopathic Hypersomnia (IH) in patients with
comorbid psychiatric disorders, mood disorders in particular, who often report symptoms
including excessive sleep duration and daytime somnolence. Further, 15-25% of patients with
IH report significant depressive symptoms. When comparing these patients groups, studies have
not found significant differences in depression scores, indicating the severity of depression
cannot be reliably used to support diagnostic distinctions. These findings present
significant challenges to the differential diagnosis of IH vs. Hypersomnia Associated with a
Psychiatric Disorder (HAPD). Indeed, the diagnostic criteria of IH and HAPD overlap
considerably, leaving clinicians to make the often challenging distinction of whether
hypersomnia symptoms are temporally related to the course of the psychiatric disorder(s).
The difficulty in differentiating IH from HAPD has largely focused on subjective sleepiness,
but some studies have utilized objective measures of sleepiness, in particular the MSLT, to
compare these groups. Vgontzas and colleagues found that IH was associated with faster sleep
onset on daytime nap opportunities compared to HAPD. Further, a systematic review and
meta-analysis found that subjective hypersomnolence in patients with mood disorders was not
associated with faster sleep latency on the MSLT compared to normative values, although there
was significant heterogeneity. This discrepancy between subjective and objective hypersomnia
can logically be explained by the presence of depressive symptoms. Depression is associated
with cognitive distortions that lead individuals to interpret events from a more negative
perspective, which leads to greater reporting of physical symptoms including pain and
fatigue. An in-depth investigation of depression in patients with IH and HAPD may shed light
on fundamental differences between these groups and improve diagnostic accuracy.
In understanding the relationship between depression and subjective hypersomnia it will be
critical to look beyond subjective depressive symptoms because there will be de facto
associations found due to the common use of self-report methods. Studies need to assess the
neurobiological domains that underlie depression, both to utilize more objective methods and
to understand the actual mechanisms driving these associations. A logical target in this
regard would be the reward system, which is activated by any pleasurable stimuli and directs
motivation to seek out these stimuli. Reward function is disrupted in individuals with
depression, leading to two core features of anhedonia, i.e reduced capacity to experience
pleasure and low motivation during waking hours. More specifically, patients with MDD
demonstrate deficits in areas of reward function, namely reduced effort for rewards,
discounting of monetary rewards, and impairments in reward learning. It also seems totoo
reasonable to expect that reward dysfunction is also related to the experience of
hypersomnia, although this has not been previously investigated. Interestingly,
investigations have recently begun to examine the ways in which sleep disturbance may
independently affect reward processes. Poor sleep at night can contribute to impaired reward
function the next day.
A second depression-related system to investigate would be the sleep/wake system. Depression
is known to be associated with abnormalities in sleep, in particular in slow wave sleep, the
most restorative type of sleep. More specifically, the quantity of slow waves during sleep
can be quantified as slow wave activity (SWA), with greater SWA associated with greater
perceptions of feeling rested the next day. Depression is associated reduced SWA, which is
thought the reflect deficient neuroplasticity. Patients with depression and hypersomnia have
been found to exhibit reduced SWA compared to those without hypersomnia, suggesting a
potential deficit in the restorative quality of sleep in these individuals. This suggests
that the SWA deficiencies may be specifically related to subjective hypersomnia in
depression. No studies have examined SWA dynamics in IH.
The overarching hypothesis is that greater severity of subjective, but not objective,
hypersomnia in patients with IH and HAPD is related to a combination of disruption in slow
wave sleep dynamics at night and deficits in reward processes. Demonstration of these effects
could improve understanding of the nature of subjective vs. objective hypersomnia and lead to
improve the differential diagnosis of hypersomnia disorders.
