# Reward Function in Adolescents with Depression and Cannabis Use

> **NIH NIH F30** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $51,752

## Abstract

PROJECT SUMMARY/ABSTRACT
 Adolescent depression and cannabis use are concurrent major public health concerns, and this comorbidity
has been associated with long-term cognitive and behavioral consequences. However, there has been sparse
research in this area, as most neuroimaging studies in adolescent depression exclude cannabis users. We seek
to address this gap based on converging evidence that: 1) Reward dysfunction contributes to maintenance and
progression of depression in adolescents; 2) Reward dysfunction is a heterogenous construct involving deficits
in diverse cognitive processes, including reward anticipation, attainment, and prediction error; 3) These deficits
entail distinct neural mechanisms that can be studied by functional magnetic resonance imaging (fMRI); 4) The
major psychoactive agent in cannabis, Δ9-tetrahydrocannabinol (THC), exerts its effects through modulation of
the cortico-striatal reward system; and 5) Cannabis use may result in temporary relief of mood and anxiety
symptoms while inducing potentially deleterious long-term neural reward alterations. We documented that
anhedonia–a core symptom of depression reflecting reward deficits–was associated with worse depression
outcomes, including chronicity and suicidality, in adolescents. Similarly, using resting-state fMRI, we found that
altered striatal intrinsic functional connectivity (iFC) with the prefrontal cortex was associated with anhedonia
severity in depressed adolescents. Further, using the reward flanker task (RFT), we found that adolescents with
diverse mood and anxiety symptoms showed weaker striatal activation during reward anticipation than healthy
controls, while stronger activation in the anterior cingulate cortex predicted worse higher levels of anhedonia at
two-year follow-up. We therefore propose a 2×2 cross-sectional study to test the overall hypothesis that comorbid
cannabis use in adolescent depression is associated with more severe neural reward deficits and clinical
symptoms. Participants will comprise 30 depressed cannabis users, 30 depressed cannabis non-users, 30 non-
depressed cannabis users, and 30 healthy controls, all ages 14-18 (Tanner stage ≥ 4) and psychotropic-
medication-free. Using resting-state and RFT task fMRI, we predict that comorbid cannabis use and depression
will be associated with more pronounced deficits in reward anticipation (Aim 1) and alterations in cortico-striatal
iFC (Aim 2) than depression alone. Further analyses (Exploratory Aims) will assess the relationships between
cannabis use frequency and activation during reward anticipation, cortico-striatal iFC, and symptom severity.

## Key facts

- **NIH application ID:** 10538021
- **Project number:** 1F30DA056227-01A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Tram Ngoc Bao Nguyen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 1
- **Project period:** 2022-08-16 → 2025-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538021

## Citation

> US National Institutes of Health, RePORTER application 10538021, Reward Function in Adolescents with Depression and Cannabis Use (1F30DA056227-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10538021. Licensed CC0.

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