# The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $113,438

## Abstract

PROJECT SUMMARY
First episodes of major depressive disorder (MDD) typically begin during adolescence. Despite the fact that
adolescent-onset MDD is associated with more severe and recurrent episodes of MDD, little work has been
done to identify mechanisms underlying depressive relapse or recurrence. Prior work by the candidate has
documented differences in functional and structural connectivity involving the anterior cingulate cortex (ACC)
between adolescents with MDD and psychiatrically healthy controls; these phenotypes are posited to reflect
altered neurodevelopment in key emotion regulation circuitry. We do not yet know, however, whether and how
MDD impacts adolescent development of ACC connectivity in a manner that contributes to an increased risk of
depressive relapse or recurrence. One mechanism may be the immune system, which activates in response to
psychosocial stressors and influences neurotransmitter systems including glutamate, the primary excitatory
neurotransmitter in the brain. Basic research indicates that higher levels of pro-inflammatory cytokines leads to
overexcitation of glutamatergic neurons to the point of neurotoxicity and, consequently, to reduced
neuroplasticity. Further, neuroimaging studies of adult MDD have reported heightened levels of inflammation
and altered levels of glutamate in the ACC. These data, combined with growing evidence that ACC
connectivity undergoes extensive maturation during adolescence, suggest that heightened inflammation and
excessive glutamate may lead to atypical development of this circuitry in adolescents with MDD. The PI
therefore seeks to test the central hypothesis that heightened inflammation acts through glutamate
transmission to disrupt typical neurodevelopment of ACC connectivity in adolescents with MDD to increase risk
of depressive relapse or recurrence. In light of barriers that hampered research training progress on the parent
K01 during COVID-19, this supplement seeks to expand the sample size of the baseline grant in order to test
this model in 75 adolescents with MDD assessed longitudinally over 18 months using an innovative multimodal
approach. The PI will assay peripheral levels of pro-inflammatory cytokines using dried blood spot technology,
noninvasively image glutamate and antioxidants in ACC using proton magnetic resonance spectroscopy, and
generate trajectories of depression symptoms based on 9 assessments over 18 months. This K01 fills key
gaps in our understanding of how inflammatory and glutamatergic mechanisms contribute to subsequent
relapse or recurrence in adolescents with MDD, and whether antioxidants protect against depression
recurrence by buffering the effects of inflammation on adolescent development of ACC circuitry. Importantly,
the candidate will execute this research in the context of receiving advanced training in stress-related immune
biology, causal inference modeling, and developmental psychopathology. Results from this project will
culminate in R-lev...

## Key facts

- **NIH application ID:** 10756332
- **Project number:** 7K01MH117442-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** TIFFANY CHEING HO
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $113,438
- **Award type:** 7
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756332

## Citation

> US National Institutes of Health, RePORTER application 10756332, The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression (7K01MH117442-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10756332. Licensed CC0.

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