# Adolescent brain maturation and psychopathology

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $805,511

## Abstract

Healthy adolescent brain maturation involves several highly coordinated processes including extensive and
dynamic reorganization of structural and functional networks and neuropil contraction. However, excessive
neuropil contraction, and impaired network reorganization may result in dysconnectivity in structural, diffusion,
and functional networks that may explain why more than 50% of psychiatric disorders begin during adolescence.
This is particularly notable in first-degree relatives of persons with schizophrenia/schizoaffective disorder (familial
high risk for schizophrenia (FHR)) possibly due to additional familial risk. Prior studies on adolescents have
examined gray matter (GM) metrics (e.g., volumes) to index neuropil changes and have studied one modality of
network, e.g., structural, or functional to elucidate network pathology. However, GM metrics do not specifically
index neuropil (cortical regions rich in synapses, dendrites, axonal endings, interneurons, glia, and unmyelinated
axons with few cell bodies). Similarly, examining individual network modality (monoplex network) does not reflect
concomitant changes in other network modalities. Therefore, we propose to examine neuropil growth/contraction
using 3D whole-brain phosphorus magnetic resonance spectroscopy (31P MRS). To elucidate alterations in
multiple modalities of networks, we will use a novel multiplex network analysis that provides composite metrics
of dysconnectivity in multiple network layers that may be closer to the ‘ground-truth’ of network pathology since
networks in the brain tissue are essentially multiplex in nature. Our goal is to longitudinally examine neuropil
growth/contraction and multiplex network dysconnectivity in relation to categorical (axis I disorders) and
dimensional (severity of cognitive/social deficits, and psychopathology) outcomes using an accelerated cohort
design on 210 subjects between the ages encompassing onset of puberty and 18 years equally distributed for
the FHR status. Our proposal is strongly supported by convergent preliminary data that show greater psychiatric
morbidity, GM loss in the fronto-temporal network (FTN) regions and altered structural, diffusion, and functional
networks among adolescent FHR persons, and impairments in selected multiplex network metrics suggesting
multiplex network dysconnectivity. We will use ultra-high field neuroimaging at 7 Tesla to obtain high resolution
MP2RAGE, 3D whole-brain 31P MRS with superior spectral resolution, diffusion weighted imaging with Neurite
Orientation Dispersion Density Imaging (NODDI) modeling, and resting fMRI, and collect psychopathological,
cognitive, and social function data at baseline, 1, and 2-years to characterize longitudinal trajectory of neuropil
growth/contraction (Aim 1), its relationship to multiplex network dysconnectivity (Aim 2) and with categorical and
dimensional outcomes. We will build an integrated model of multiplex network features and neuropil growth/
contractio...

## Key facts

- **NIH application ID:** 10940639
- **Project number:** 1R01MH137090-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Konasale M Prasad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $805,511
- **Award type:** 1
- **Project period:** 2024-08-09 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940639

## Citation

> US National Institutes of Health, RePORTER application 10940639, Adolescent brain maturation and psychopathology (1R01MH137090-01). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10940639. Licensed CC0.

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