# Psychosis-related Physiological and Neuronal Phenotypes in 22q11 Deletion Syndrome

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $648,384

## Abstract

Project Summary
In this revised proposal, we plan to examine the physiological and synaptic properties of
pluripotent stem cell (iPSC)-derived neurons, as well as schizophrenia (SCZ)-related
physiological phenotypes, gathered from patients with 22q11 Deletion Syndrome (22q11DS).
The syndrome associates with a 20-30 fold increase in the risk for schizophrenia. 20-30% of
patients with 22q11DS develop SCZ by early adulthood. The acoustic startle response (ASR) is
an evolutionarily conserved reflex, aspects of which differ in SCZ compared to healthy controls.
Prior work on non-22q11DS individuals at high risk for SCZ based on their phenotypic
characteristics (i.e., those with prodromal symptoms) suggest that the latency of ASR predicts
conversion to SCZ. Mismatch negativity (MMN) is an evoked potential in response to unusual or
“oddball” acoustic stimuli imbedded within a train of repetitive acoustic stimuli. Impaired
generation of an enhanced response to the oddball stimuli is the well-replicated MMN
abnormality seen in SCZ. Our proposed work will examine ASR measures and MMN in older
adolescents and young adults with 22q11DS (and healthy controls) to test the hypothesis that
latency of the ASR and/or MMN will predict severity of prodromal symptoms, and ultimately
conversion to SCZ, in this genetically defined high-risk group. Simultaneously we will study
potential cellular mechanisms related to ASR and MMN in iPSC-derived neurons from 22q11DS
patients exhibiting extreme values of latency to startle in the ASR. We hypothesize that doing so
will identify potential cellular mechanisms underlying the phenotypic impact of the 22q11
deletion (including elevated risk for SCZ). This research will thus shed light on how genetic
mechanisms alter cellular properties relevant to clinical and physiological differences observed
in SCZ and the SCZ prodrome.

## Key facts

- **NIH application ID:** 10468740
- **Project number:** 5R01MH117315-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Joseph F. Cubells
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $648,384
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468740

## Citation

> US National Institutes of Health, RePORTER application 10468740, Psychosis-related Physiological and Neuronal Phenotypes in 22q11 Deletion Syndrome (5R01MH117315-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10468740. Licensed CC0.

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