# Multidimensional aging trajectories in mid to late-life psychosis (MAP)

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $1,082,757

## Abstract

Even though schizophrenia spectrum disorders (SSD) are generally considered to be neurodevelopmental in
origin, emerging evidence supports the idea that aberrant brain aging may also occur. Because this concept has
only recently reemerged, data on characteristic phenotypical and brain age-related trajectories in SSD and their
underlying mechanisms remain sparse. These critical knowledge gaps constitute major obstacles in identifying
actionable treatment targets for aberrant aging in SSD. Our proposal has two overarching goals: (1) address
existing knowledge gaps in age-related changes in SSD and (2) identify actionable targets for novel interventions
designed to ameliorate, or even prevent, aberrant aging in SSD.
A considerable body of work in geroscience suggests that normal aging phenomena are present at multiple
levels. Specifically, age-related declines in brain structures and cognitive function are well established. Recent
findings also suggest that energy metabolism (bioenergetics) in the brain, which is critical for brain plasticity and
cognition, is negatively affected by aging. Emerging data further supports the idea that these phenomena are
intricately connected and point towards bioenergetic aging as a potentially driving force behind structural brain
aging and cognitive aging. These principles of aging in the general population provide the conceptual framework
of our project.
We propose to leverage state-of-the-art multimodal neuroimaging techniques and tailored cognitive tasks to
systematically evaluate age-related changes in brain structure, function, and bioenergetics in the dorsal anterior
cingulate cortex (dACC), which is considered a hallmark brain region implicated in the pathophysiology of SSD
and plays a critical role in nonsocial and social cognition. Over a period of 5 years, we will enroll 120 individuals
with SSD and 120 demographically matched controls. We will quantify (1) cortical thickness deviations in the
dACC using novel normative reference models, (2) social cognition and nonsocial cognition with a tailored
behavioral battery and task fMRI, and (3) in vivo spectroscopic indices of bioenergetics in the dorsal ACC (dACC)
using ultra-high-field MR spectroscopy (MRS). We will determine if these measures of patients differ from those
of healthy volunteers (Aim 1) and if the effect of age on these measures differs between patients and controls
(Aim 2). We will also explore whether age trajectories converge across measures in an exploratory aim.
The findings of this project could offer mechanistic insights into aging process in SSD by focusing on multiple
units of analysis and provide actionable treatment targets for aberrant aging in SSD.

## Key facts

- **NIH application ID:** 10805088
- **Project number:** 1R01MH135451-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Nina Vanessa Kraguljac
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,082,757
- **Award type:** 1
- **Project period:** 2023-12-15 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805088

## Citation

> US National Institutes of Health, RePORTER application 10805088, Multidimensional aging trajectories in mid to late-life psychosis (MAP) (1R01MH135451-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10805088. Licensed CC0.

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