# Investigating the Role of Slow-wave Activity as a Marker of Impaired Plasticity in Major Depressive Disorder

> **NIH NIH K23** · UNIVERSITY OF PENNSYLVANIA · 2021 · $182,980

## Abstract

PROJECT SUMMARY
Major
second
Depressive Disorder (MDD) is the most prevalent mental illness, and has been estimated to be the
leading cause of disability worldwide. However, standard treatments for MDD typically take at least 2-3
weeks to take effect, prolonging disease burden. In order to create novel, fast-acting therapies, a better
understanding of the underlying mechanisms responsible for the development and maintenance of MDD is
needed. It
ketamine
MDD.
 is hypothesized that the common factor among current rapid antidepressant interventions, including
and sleep deprivation, is a change i n synaptic plasticity, which has been suggested to be impaired in
Slow-wave activity (SWA) during sleep has been implicated in modulating synaptic plasticity; however
the link between SWA, plasticity, and depression has yet to be determined. The proposed research aims to
examine the role of sleep SWA in modulating mood by testing the model that disrupting SWA during sleep can
prevent homeostatic decreases in plasticity, thereby increasing plasticity and improving mood in individuals
with MDD. In this Mentored Patient-Oriented Research Career Development Award (K23) application, the
candidate will pursue these research aims in the context of interdisciplinary training that builds on her expertise
in the role of sleep homeostasis in depression and sleep research methodology with (1)
neuroscience
stimulation,
including
clinical
training in the
of synaptic plasticity and multi-modal assessment methods (e.g., transcranial magnetic
analysis of waking EEG, measurement of BDNF), (2) advanced training in quantitative EEG
analytic approaches, and (3) advanced training in MDD research (e.g., neurobiology of MDD, and
trials methodology).These training goals will support the candidate's long term goal of becoming an
independent translational scientist in patient-oriented research, and are central to the execution of the
proposed research plan. Forty
history
 males and females with MDD (25-50 yo), and a group of twenty controls with no
of mood disorders will spend two nights in the laboratory: one baseline night of sleep, and one night
where slow-wave sleep will be disrupted utilizing a validated procedure. Following
markers
indirect
serum
will
wave
 each laboratory night,
 associated with net synaptic strength and plasticity will be assessed using several independent, but
 indices including waking EEG theta power metrics derived from t ranscranial magnetic stimulation,
derived BDNF, and behavioral measures of learning and memory. It is predicted that those with MDD
exhibit markers associated with deficient net synaptic strength and plasticity at baseline, and that slow-
disruption will normalize these measures, thereby improving mood
,
. This project has the potential to
identify the mechanisms by which sleep affects mood in MDD, which could inform the development of novel
interventions.

## Key facts

- **NIH application ID:** 10220693
- **Project number:** 5K23MH118580-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jennifer Rachel Goldschmied
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $182,980
- **Award type:** 5
- **Project period:** 2019-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220693

## Citation

> US National Institutes of Health, RePORTER application 10220693, Investigating the Role of Slow-wave Activity as a Marker of Impaired Plasticity in Major Depressive Disorder (5K23MH118580-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220693. Licensed CC0.

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