# Imaging transcriptomics across developmental stages of early psychotic illness

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $196,560

## Abstract

PROJECT SUMMARY/ABSTRACT
 As a physician-scientist in neurodevelopmental research with a strong background in molecular
neuroscience, I seek mentored support for training in novel analytics to integrate neuroimaging and molecular
genetics data in humans, on my path toward becoming an independent investigator. I propose an integrative
project focusing on a prospective longitudinal cohort of youth at clinical high risk (CHR) for psychosis (NAPLS2)
that utilizes advances in neuroimaging analyses and high throughput, publicly available brain-wide transcriptomic
atlases to investigate neurodevelopmental mechanisms of schizophrenia (SZ) risk. Prior work suggests that
cognitive dysfunction is a core feature of SZ, with working memory (WM) typically maturing throughout
adolescence when overt clinical psychosis onset is most common, and WM depends, in part, on widely
distributed cortical glutamate- and GABA-mediated neural circuitry. However, prevention and treatment of
cognitive dysfunction in SZ is limited. This project incorporates cross-sectional and longitudinal in vivo
neuroimaging data from the NAPLS2 cohort with publicly available human postmortem brain transcriptome data
to test whether morphometric similarity networks and cognitive impairments are differentially affected in CHR
youth that develop psychosis, whether these cortical patterns are linked to behavioral measures of WM, and
whether affected frontotemporal regions have a unique pattern of glutamate/GABA transcript enrichment affected
by SZ risk genes. If these hypotheses are confirmed, the project will provide evidence that cortical alterations
are detectable prior to overt illness onset and associated with behavioral and molecular measures of cognitive
dysfunction.
 To attain these research aims, I seek formal training in imaging genomics and longitudinal analysis
methods, which is possible through structured coursework, mentoring from a team of distinguished scientists,
and UCLA’s outstanding infrastructure for genomics, neuroimaging, and psychosis research. The primary mentor
(Dr. Bearden) has internationally recognized expertise in psychosis and prospective longitudinal studies of
related neurocognitive and neuroimaging phenotypes, with extensive experience as a successful research
mentor. The core co-mentors have complementary expertise in bioinformatics and functional genomics (Dr.
Gandal) and statistical genetics methods (Dr. Pasaniuc) critical for this proposal. My collaborator (Dr. Raznahan)
has renowned expertise in developmental neuroimaging. A key consultant (Dr. Freimer) will allow for shared
bioinformatics resources and core facilities to guide analyses in large-scale functional and developmental
genomics approaches, and will provide focused training in lab leadership and career development. This K
proposal will provide me with the in-depth training in research methodology and career support necessary for a
successful transition to independence. This proposal aligns with th...

## Key facts

- **NIH application ID:** 10788461
- **Project number:** 5K23MH129826-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** GIL D HOFTMAN
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,560
- **Award type:** 5
- **Project period:** 2023-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788461

## Citation

> US National Institutes of Health, RePORTER application 10788461, Imaging transcriptomics across developmental stages of early psychotic illness (5K23MH129826-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10788461. Licensed CC0.

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