# COVID-19, Inflammation and HPA axis activity, and Risk for Psychopathology in Youth

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $788,640

## Abstract

There has been an unprecedented mental health crisis and a surge in suicidal thoughts and behaviors (STBs)
among youth that predated and was further exacerbated by the pandemic. Studies show that youth are at
increased risk for incident treatment for psychiatric diagnosis 1-6 months following COVID-19 infection. Risk for
STBs is also increased among individuals with infections; and cognitive impairment following COVID-19 is
reported even ~4 months following infection. In addition to the increased morbidity and mortality, the mitigation
efforts put in place to reduce transmission resulted in additional stressors on children and families (e.g., parental
job loss, parental death, online schooling) and these were associated with increased rates of psychopathology
in youth. However, we have a limited understanding of the unique contribution of COVID-19 infection on
incidence of psychopathology in youth and the biological mechanisms implicated in risk. Dysregulations in
immune responses, specifically, increased IL-6, IL-1b, C-Reactive Protein (CRP), and TNF-a and their mRNA
and low cortisol are common biological mechanisms implicated in COVID-19 severity and in psychopathology.
Our goals are to examine the impact of COVID-19 infection on incidence of psychopathology in youth; its impact
on inflammation and HPA axis markers; and to identify clinical, cognitive, biological, and psychosocial
characteristics that will help predict youth at risk for onset of psychopathology following COVID-19 infection. We
propose to recruit youth, aged 12-17 years, without history of psychiatric disorders or chronic Illness or chronic
infections who were: 1) infected with COVID-19 within the past month (COVID, n=200); 2) without history of
COVID-19, influenza (IFV), or any respiratory infections in the past 6 months (no-COVID, n=200); and 3) youth
with IFV within the past month (IFV, n=100). The IFV group will allow us to examine whether COVID-19 or
infections in general are associated with risk. Participants will be followed at 3, 6, and 18 months after baseline
and assessed on psychiatric and physical symptoms, cognitive function, incident psychopathology; pandemic
and non-pandemic stressors; and risk and protective factors at all timepoints. At baseline, 3, and 6 months, we
will measure inflammation (cytokines, mRNA for inflammatory genes); and collect acute and chronic HPA axis
activity measures (hair cortisol concentrations, salivary cortisol). We hypothesize that the COVID group will show
increased risk of onset of psychopathology, specifically depression and anxiety disorders and STBs, compared
to the no-COVID and IVF groups. They will also show increased inflammation and psychiatric and physical
symptoms over time; and reduced HPA axis activity and cognitive function over time; and these will in turn predict
onset of psychopathology. This study will advance our understanding of the impact of COVID-19 infection on
risk for psychopathology in youth and the biological...

## Key facts

- **NIH application ID:** 10876413
- **Project number:** 5R01MH134487-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Nadine M. Melhem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $788,640
- **Award type:** 5
- **Project period:** 2023-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876413

## Citation

> US National Institutes of Health, RePORTER application 10876413, COVID-19, Inflammation and HPA axis activity, and Risk for Psychopathology in Youth (5R01MH134487-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876413. Licensed CC0.

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