# Genetics to Brain Biomarkers in Kynurenine Pathway Dysfunction

> **NIH NIH P50** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $764,303

## Abstract

Project summary
Perturbations in the kynurenine pathway metabolites have been associated with alterations in glutamate,
acetylcholine, serotonin and dopamine signaling, and have been linked to schizophrenia. During the first 5 year
of the Conte project, we have developed new evidence that kynurenergic effects in schizophrenia maybe
dynamically related to stress response and genetics. Identifying the underlying mechanism would be critical to
determine whether this pathway is critical in schizophrenia and how it is related to the known
pathophysiological glutamate, acetylcholine, serotonin and dopamine signaling in this illness. The downstream
substrates of the tryptophan-kynurenine mechanism involve multiple and frequently opposite actions. Although
many of these actions have implications in schizophrenia, the field lacks a coherent schizophrenia-kynurenine
model, hindering meaningful preclinical-clinical translations. The difficulty may be due to the inherent
complexity of the system and its interactions with genetics and developmental risk factors. We will employ a
combination of cellular to patient ex-vivo cellular genetic approaches to analyze the role genetic effects on the
kynurenine pathway signaling in schizophrenia. The empahsis is on stress-induced kynurenergic response and
its associated brain circuitry and glutamatergic signaling biomarkers. The project is ambitious and translational,
involving clinical, brain imaging, and cellular models for specific genetic effects. However, we have formed a
strong, highly integrated team and project design, and the preliminary studies support our proposed specific
aims, demonstrate feasibility, and suggest a significant potential for novel discoveries if these aims are
supported in the proposed studies. Knowledge on how the kynurenine pathway is involved in clinical
schizophrenia patients will lead to more specific and better treatment targets for drug development.

## Key facts

- **NIH application ID:** 10016396
- **Project number:** 5P50MH103222-07
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** L Elliot Elliot Hong
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $764,303
- **Award type:** 5
- **Project period:** 2014-05-09 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016396

## Citation

> US National Institutes of Health, RePORTER application 10016396, Genetics to Brain Biomarkers in Kynurenine Pathway Dysfunction (5P50MH103222-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10016396. Licensed CC0.

---

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