# Depression Response to Fast-Acting Treatments: Inflammation and Reward Mechanisms

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $197,640

## Abstract

PROJECT SUMMARY/ABSTRACT
High inflammation is a biological characteristic associated with poorer response to antidepressant medication.
Anhedonia, representing a facet of reward system dysfunction, is a common symptom of depression, and also
predicts poor therapeutic response. Recent literature suggests that these variables (one biological, the other
behavioral) are linked. However, no research has simultaneously addressed whether both of these dimensional
characteristics—higher inflammation and greater reward deficits—impact depression treatment outcome, with
consideration of levels at baseline as well as dynamic, longitudinal changes following treatment.
Electroconvulsive therapy (ECT) and ketamine both elicit robust and rapid antidepressant response in patients
with severe and treatment resistant depression. Thus, these treatment modalities are ideal for testing dynamic
links between inflammation, behavioral constructs of reward, and treatment outcomes within a relatively short
time frame. Furthermore, contrary to inflammation predicting poor outcome to antidepressant pharmacotherapy,
our preliminary data show that higher baseline inflammation (as indexed by interleukin [IL]-6) predicts better
treatment response to ECT (n=29, p=0.01). Moreover, ketamine has also been theorized to be more effective
for depressed patients with high inflammation, and some initial clinical results support this hypothesis. However,
data are sparse, inflammatory assessments are limited, and at least one ketamine study has failed to replicate
earlier results. Notably, reward deficits have not been formally evaluated as a predictor of response to ECT nor
ketamine. We have the unique opportunity to leverage a large funded U01 study, “Perturbation of the treatment
resistant depression connectome by fast-acting therapies” (PI Narr, U01 MH110008, 09/16-05/20) to investigate
relationships between inflammation, reward processes, and treatment outcome, within and across ECT and
ketamine. Neither inflammation nor a comprehensive assessment of reward processes are examined in the
parent grant. The goals of this proposal are thus unique and do not overlap with those of the U01. Here, we
propose to comprehensively capture a vertically integrated assessment of inflammation including systemic
levels, upstream cellular production, and transcription factor activation, and to evaluate both reward motivation
and reward responsiveness via behavioral tasks and self-report. Our central hypothesis is that inflammation will
link with deficits in reward, and will impact treatment outcome. Determination of differences in treatment response
based upon linked clinical phenotypes and inflammatory profiles would be ground-breaking, informing more
effective personalized treatment strategies for depressed patients with elevated inflammation. This K23
integrated training and research program is designed to prepare the candidate to become a clinical translational
depression researcher, with expertis...

## Key facts

- **NIH application ID:** 9999036
- **Project number:** 5K23MH116127-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jennifer Kruse
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,640
- **Award type:** 5
- **Project period:** 2018-09-10 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999036

## Citation

> US National Institutes of Health, RePORTER application 9999036, Depression Response to Fast-Acting Treatments: Inflammation and Reward Mechanisms (5K23MH116127-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999036. Licensed CC0.

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