# Gamma oscillations as a prognostic marker for ketamine therapy in treatment resistant depression

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2024 · $200,000

## Abstract

Project Summary
Treatment-resistant depression (TRD) is a significant public health issue and the leading cause of disability in
young and middle-age adults. The FDA's approval of esketamine nasal spray for TRD and the rapid proliferation
of clinics providing ketamine (KET) has markedly increased numbers of patients receiving these interventions.
However, we lack valid and reliable biological or clinical markers that predict treatment success for an initial
course of KET therapy. Electroencephalography (EEG) gamma band power is a neurophysiological measure of
cortical excitability and synaptic potentiation. These processes are implicated in KET’s mechanism as a NMDA
receptor channel antagonist, making gamma power a candidate biomarker. The broad, long-term objective of
this R21 application is to optimize the rational selection of patients with TRD who benefit from rapid-acting
antidepressant therapies such as KET or esketamine. To achieve this goal, we examine gamma band
potentiation (KET induced power increase) in treatment-seeking TRD patients (N=60) scheduled to receive an
induction course of KET therapy (twice weekly infusions for 4 weeks) from a partner community-based clinic. To
examine gamma potentiation, we conduct a pharmaco-EEG challenge entailing a fixed-order infusion of saline
followed by KET while recording resting-state and evoked gamma oscillatory activity. To characterize the unique
effects of psychotropic medication resistance, we include an age- and sex-matched major depressive disorder
(MDD) group (N=20), and an age- and sex-matched healthy control (HC) group (N=20). In AIM 1, we examine
baseline patterns of gamma band power and potentiation in TRD patients compared to MDD and HCs. We
hypothesize that patients with depression (TRD/MDD) will have lower baseline gamma power than HCs, and
that patients with TRD will show greater gamma potentiation in response to KET, compared to non-treatment
resistant MDD patients and HCs. In AIM 2, we determine the relevance of gamma band potentiation to the
antidepressant mechanism of action of KET for TRD patients who receive an induction course of KET therapy.
We hypothesize that greater reduction in depressive symptoms during the induction phase of KET therapy is
associated with a higher level of gamma potentiation in response to the first infusion of KET. An innovative
exploratory aim is to investigate the stability of gamma band potentiation at the midpoint of the KET induction
course of treatment and its relationship with clinical outcomes. This project is significant because the current
trial-and-error approach to TRD therapeutics highlights the urgent need for personalized care. Our study’s
potential to efficiently capture gamma dynamics across a spectrum of depressed patients provides strong
innovation. Finally, this project is impactful because, if successful, it provides a compelling rationale for a larger
prospective investigation of gamma dynamics as a moderator of outcome to vari...

## Key facts

- **NIH application ID:** 10799447
- **Project number:** 1R21MH133198-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** SANJAY J MATHEW
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $200,000
- **Award type:** 1
- **Project period:** 2024-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799447

## Citation

> US National Institutes of Health, RePORTER application 10799447, Gamma oscillations as a prognostic marker for ketamine therapy in treatment resistant depression (1R21MH133198-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10799447. Licensed CC0.

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