# Biopsychosocial Phenotypes and Potential Mechanisms in CHARTER

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $40,698

## Abstract

PROJECT SUMMARY
People with HIV (PWH) experience a diverse set of CNS complications including cognitive and mood
disorders. CNS complications may occur even in individuals taking antiretroviral therapy (ART) to suppress
HIV RNA, moreover, recent studies suggest HIV infection may accelerate aging among PWH. However,
accelerated aging has not been carefully examined in the context of brain structure and may be complicated by
the diversity in CNS complications among PWH. Studies based on magnetic resonance imaging (MRI) show a
relationship between accelerated biological aging and accelerated brain atrophy. The proposed study aims to
calculate “brain age”, which is a marker of biological aging estimated from structural neuroimaging variables,
including cortical thickness and subcortical volume. Estimated brain age found to be greater than an
individual’s chronological age is thought to reflect an accumulation of age-related changes to the brain. To
better characterize the mechanisms of central nervous system (CNS) biotypes in people with HIV (PWH), the
proposed supplement aims to extract cortical thickness and subcortical volume measures derived from MRI
scans to compare estimated brain age to chronological age, telomere length and mitochondrial DNA copy
numbers (biological markers of aging). The project is leveraged through the parent proposal (R01MH12520-
02), which will use clustering methods to assess CNS biotypes in PWH. Supplement Specific Aim 1 is to
estimate brain age in the cohort using a composite measure of cortical thickness and subcortical volume to
compare it to chronological age and biomarkers of biological aging. We propose to use a Least Absolute
Shrinkage and Selection Operator (LASSO) regression to derive brain age, a method that works well with
limited sample sizes. We hypothesize that cortices will be thinner (consistent with older brain age) among PWH
who have adverse CNS biotypes when compared to the reference group of PWH who perform as expected on
assessments of cognition, mood, and daily functioning. Supplement Specific Aim 2 is to determine how brain
age relates to different CNS biotypes identified by machine learning in the parent project and how brain age
relates to historical HIV-Associated Neurocognitive Disorders diagnosis. We will include health-related
variables as covariates in the model, since they are associated with cognitive decline and older brain age. For
example, cardiovascular risk factors, high levels of alcohol intake, and stroke risk score are associated with
brain aging. We also hypothesize that estimated brain age will be accelerated among PWH with adverse CNS
biotypes compared to the reference group of PWH. Disentangling the cognitive and biological effects of HIV in
older adults and their relation to mental health will advance the HIV field through informing our understanding
of mental health conditions among people with HIV. This proposed diversity supplement will provide the
applicant with critical ...

## Key facts

- **NIH application ID:** 10706855
- **Project number:** 3R01MH125720-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** RONALD J. ELLIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,698
- **Award type:** 3
- **Project period:** 2020-12-08 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10706855

## Citation

> US National Institutes of Health, RePORTER application 10706855, Biopsychosocial Phenotypes and Potential Mechanisms in CHARTER (3R01MH125720-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10706855. Licensed CC0.

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