# A Targeted Intervention of a Putative Striatal Subtype of Pharmacoresistant Depression

> **NIH NIH K23** · STANFORD UNIVERSITY · 2021 · $193,036

## Abstract

PROJECT SUMMARY
Major depression is the leading cause of disability worldwide, affecting over 300 million people. Individuals
with treatment-resistant depression (TRD) experience the greatest toll, with double the risk of suicide,
particularly prolonged suffering, and greater use of resources. Anhedonia, the inability to feel pleasure, is
among the most important risk factors for the development of TRD. Because anhedonia implicates
dysfunction in key regions of the brain’s reward circuits, these regions are viable mechanistic biomarkers
for testing engagement of novel interventions for depressed people who do not respond to currently
available antidepressants. In this K23 proposal, I will deploy a novel target-engagement design to evaluate
a biomarker and alternative intervention approach for anhedonia in TRD. I target D3 receptor agonism with
pramipexole and evaluate the effects on a reward circuit biomarker of interest, the ventral striatum (VS),
as well as clinical, functional, and suicidality outcomes in TRD patients with prominent anhedonia. First, I
will determine whether reward task-evoked VS activation changes in a group of TRD subjects as a result
of treatment with pramipexole after 8 weeks; second, evaluate whether anhedonia measures, function, and
suicidality change in the same group after 8 weeks of treatment with pramipexole; and third, assess whether
baseline ventral striatal activation is associated with change in VS activation and clinical outcomes. This
K23 proposal and accompanying training plan would enable me to receive advanced training in three key
areas: the analysis and interpretation of functional neuroimaging data, traditional and biomarker-guided
clinical trials, and biomarkers across multiple domains. Furthermore, I have assembled an interdisciplinary
mentorship team ideally suited to guiding me through this project, consisting of leaders in functional
neuroimaging (Dr. Leanne Williams, Primary Mentor), biomarkers in depression (Dr. Andrew Krystal,
Collaborator), depressive disorders and traditional clinical trials (Dr. Alan Schatzberg, Co-Mentor), statistics
and innovative clinical trial design (Dr. Philip Lavori, Collaborator), reward processing (Dr. Michael
Treadway, Collaborator), and neuroimaging-guided trials in major depressive disorder (Dr. Boadie Dunlop,
Collaborator). Furthermore, as part of my training, I intend to continue clinical work during the period of my
Career Development Award, launching my own consultation clinic for patients with treatment-resistant
mood disorders facilitated under the umbrella of the Mood Disorders Center at Stanford during the latter
years of the Award. Conducting clinical work together with research will ideally position me to ask scientific
questions and implement study designs that explicitly translate key discoveries from basic science into
guidance for clinical decision-making. This proposal will be carried out at Stanford University, a world
renowned hub of neuroscience an...

## Key facts

- **NIH application ID:** 10215873
- **Project number:** 1K23MH123894-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Laura Michele Hack
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-05-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215873

## Citation

> US National Institutes of Health, RePORTER application 10215873, A Targeted Intervention of a Putative Striatal Subtype of Pharmacoresistant Depression (1K23MH123894-01A1). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10215873. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*