# Biomarkers and Mechanisms of Stress Pathophysiology in Early Schizophrenia

> **NIH NIH K23** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $190,836

## Abstract

Abstract
Stress is a major factor contributing to development of psychiatric disorders, including
schizophrenia. Previous studies have revealed possible abnormalities in the hypothalamic-
pituitary-adrenal (HPA) axis in schizophrenia, with evidence that schizophrenia patients show
abnormal levels of cortisol, the main stress hormone, in response to stress . Cortisol primes the
body to respond to stress, but also suppresses inflammatory activity that could be detrimental to
health. There is increasing evidence that schizophrenia is characterized by a state of low-grade
inflammation, though the origin and consequences of this inflammation are unknown. Both
cortisol and inflammatory markers may have effects on the brain, and conversely, the brain may
exert top-down control over cortisol and immune responses to stress. This K23 mentored
clinical research project, submitted by Principal Investigator Dr. Joshua Chiappelli, will compare
individuals with schizophrenia to healthy controls in how they respond to laboratory based
stressful challenges, including a psychological stressor and a somatic stressor that involves
exposure to pain. Levels of cortisol and IL-6 will be measured in saliva samples collected before
and after these stress challenges to examine if schizophrenia patients have an abnormality in
the normal suppression of inflammation by cortisol. Levels of glutamate in the brain will be
examined with magnetic resonance spectroscopy (MRS) concurrently with cortisol and IL-6 to
test if peripheral responses to stress are modulated by the brain. This project will take place at
the Maryland Psychiatric Research Center (MPRC), part of the University of Maryland School of
Medicine. The MPRC operates several outpatient clinics specializing in care of schizophrenia
patients as well as a MR imaging center; the research programs of the MPRC include preclinical
and clinical research studies focusing on the causes, course, and treatment of schizophrenia.
The K23 proposal also includes a comprehensive training plan to facilitate Dr. Chiappelli’s
development into an independent clinical researcher. Mentorship will be provided by Dr. Elliot
Hong, an expert in schizophrenia and neuroimaging; Dr. Laura Rowland, an expert in use of
magnetic resonance spectroscopy in schizophrenia; Dr. Leonardo Tonelli, an expert on
neuroimmunology; and Dr. Diana Fishbein, an expert on stress and development. This project
will provide preliminary data for further R01 investigations into the mechanisms of stress
pathophysiology in schizophrenia and will provide Dr. Chiappelli with the necessary education
and skill development to lead further translational studies as an independent clinical
investigator.

## Key facts

- **NIH application ID:** 9891098
- **Project number:** 5K23MH112010-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joshua Chiappelli
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,836
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891098

## Citation

> US National Institutes of Health, RePORTER application 9891098, Biomarkers and Mechanisms of Stress Pathophysiology in Early Schizophrenia (5K23MH112010-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9891098. Licensed CC0.

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