# Cytomegalovirus, Brain Alterations, and Depression: Decoding Neuroinflammatory Pathways for Effective Intervention

> **NIH NIH K01** · LAUREATE INSTITUTE FOR BRAIN RESEARCH · 2024 · $161,658

## Abstract

PROJECT ABSTRACT/SUMMARY
Depression affects at least one in every six people, and identifying targetable risk factors is urgently needed to
facilitate early intervention and prevention. The literature and the applicant's pilot studies suggesting the
neurotropic herpes virus, such as cytomegalovirus (CMV) infection, is capable of inducing neuroinflammation,
which has been established as an important factor that contributes to the development of depression in
vulnerable individuals. The objective for the proposed K01 award is to use CMV infection as a model to
develop a comprehensive understanding that CMV infection-associated neuroinflammatory mechanism
predicts disruption of frontotemporal circuitry and increased odds of depression. The applicant will use a
multifaceted approach to understand the potential neurobiological pathways that may increase the risk of
depression in individuals with CMV infection. This approach includes the use of existing blood-based
serological markers to determine CMV serostatus and antibody levels, diffusion-weighted neuroimaging to
assess brain microstructure integrity, polygenic score methods to prove host anti-CMV immunity, and
behavioral assessments to identify depression cases and matched controls, as well as depressive symptoms,
within the UK Biobank dataset. The proposed research aims to: (1) determine the associations between CMV
seropositivity, brain alterations, and depression using the largest serological sample so far; (2) investigate links
between genetic predisposition to CMV seropositivity, brain alterations, and depression; and (3) explore
genetically predicted inflammatory molecular pathways through which CMV infection may affect brain integrity
and depressive symptoms. This study will employ rigorous methods to elucidate the role of CMV in brain
alteration and depression, which can lead to an actionable target to mitigate neuroinflammation and reduce
depression risk. The innovative approach leverages polygenic scores to capture individual genetic differences
in host immunity, offering an opportunity to identify at-risk individuals and investigate the inflammatory
mechanisms involved. This Career Development Award builds upon the applicant's neuroimaging expertise
and prior research focus, and further provides training to: (1) bridge the knowledge gap on viral epidemiology
in the context of mental health; (2) refine the understanding of the disrupted brain circuits and their relationship
with the clinical symptoms of inflammation-associated depression; (3) apply statistical genetics to probe
individual differences in immunity; and (4) develop professional skills and transition to independence. The
proposed research and training will be mentored by a team of leading experts with diverse, complementary
expertise, ensuring successful outcomes. Upon completion of this award, the applicant will be well-prepared for
an independent research career in population immunopsychiatry, focusing to (1) gain a mechan...

## Key facts

- **NIH application ID:** 10866233
- **Project number:** 1K01MH136403-01
- **Recipient organization:** LAUREATE INSTITUTE FOR BRAIN RESEARCH
- **Principal Investigator:** Haixia Zheng
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,658
- **Award type:** 1
- **Project period:** 2024-05-17 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866233

## Citation

> US National Institutes of Health, RePORTER application 10866233, Cytomegalovirus, Brain Alterations, and Depression: Decoding Neuroinflammatory Pathways for Effective Intervention (1K01MH136403-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10866233. Licensed CC0.

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