# Identifying Positive Valence System Neural Deficits in Adolescent Depression

> **NIH NIH R21** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2022 · $190,520

## Abstract

Project Summary
 Major depressive disorder (MDD) is a leading cause of disability worldwide and has a peak period of onset
during adolescence. Most individuals with MDD will experience multiple episodes over their life course, relating
to poor outcomes, suicide risk, and large personal and public health burden. Thus, identifying mechanisms of
MDD illness and course is critical to identify novel intervention targets.
 MDD is characterized by deficits within the RDoC Positive Valence System (PVS), particularly reward-related
and motivational alterations that rely on dopamine (DA) brain systems. While DA functioning has been examined
in adults using Position Emission Tomography (PET), the use of radioisotope tracers makes PET invasive and
untenable for pediatric research. As an alternative, the current study leverages a novel, fast, and non-invasive
MRI acquisition sensitive to neuromelanin (NM) to probe midbrain DA function in youth with remitted MDD.
 Further, we expect midbrain DA to contribute to alterations in key PVS domains disrupted in depression.
Specifically, the current study examines effort discounting–the process by which individuals calculate the cost-
benefit of expending effort to achieve reward. Effort discounting is shown in animal work to rely on midbrain DA
and to activate striatal regions in human MRI studies. Deficits in effort discounting, a critical part of motivation,
likely contributes to anhedonic symptoms in depression. Although alterations are noted in adult MDD, the neural
encoding of effort discounting has yet to be tested in adolescents with depression.
 The current R21 aims to address several critical gaps by probing the PVS across multiple units of analysis
in 14-17-year-olds with depression (MDD = 30) and matched healthy controls (HC = 30), capitalizing on a recently
funded R01 (MH119771-01A1) for recruitment and clinical assessment. First, Aim 1 will test, for the first time,
whether adolescents with MDD exhibit hypothesized reductions in DA functioning in key midbrain regions, the
substantia nigra and ventral tegmental area, as indexed by NM-MRI. Further, we will examine whether
adolescents with MDD exhibit blunted neural encoding of effort discounting in the ventral striatum via fMRI and
will explore whether midbrain NM mediates these differences. Second, Aim 2 will test whether these neural
markers improve prediction of real-world functioning in these adolescents using an innovative smartphone app
for deep, digital phenotyping. This will include both unobtrusive, passive sensing of daily physical activity, as an
index for motivational capacity, as well as repeated self-report of positive affective and anhedonic symptoms
during everyday functioning via ecological momentary assessment. Last, Aim 3 will test the ability of these neural
markers to predict the worsening of depressive and anhedonic symptoms over a 6-month follow-up. In summary,
this project has the promise to identify DA and PVS deficits that contrib...

## Key facts

- **NIH application ID:** 10414992
- **Project number:** 5R21MH125044-02
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** David Pagliaccio
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,520
- **Award type:** 5
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414992

## Citation

> US National Institutes of Health, RePORTER application 10414992, Identifying Positive Valence System Neural Deficits in Adolescent Depression (5R21MH125044-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414992. Licensed CC0.

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