# Biomarker Validation to Improve Cognitive and Psychosocial Outcomes in Veterans with Chronic Psychosis

> **NIH VA IK1** · VA SAN DIEGO HEALTHCARE SYSTEM · 2021 · —

## Abstract

In response to RX-20-005, this Career Development Award-1 (CDA-1) will provide a mentored research
experience and training program for an early career psychiatrist, committed to the care and wellbeing of
Veterans, to develop as a VA RR&D Investigator. Cognitive impairment causes significant disability for
Veterans with schizophrenia and limits their ability to function independently in the community and enjoy an
optimal quality of life. This application aims to improve functional outcomes for Veterans with schizophrenia
through the continued development of a promising biomarker linked to a mechanistic model of cortical function
in schizophrenia. This biomarker will ultimately be used to predict the response to therapeutic interventions
applied within VA rehabilitative settings.
 Evidence emerging from cognitive remediation suggests that schizophrenia patients can experience
clinically meaningful improvement in cognitive functioning; however, a substantial portion of patients show
minimal or no response. Biomarkers that could prospectively identify subgroups of patients most “sensitive” to
the beneficial effects of cognitive remediation and other pro-cognitive interventions could substantially improve
the efficacy of these treatments. Recently, a novel biomarker extracted from spectral properties of
electroencephalographic recordings has been proposed as an index of cortical excitation and inhibition balance
(“E/I balance”). We reported (Molina et al., 2020) that this measure was abnormal in patients with
schizophrenia. We also demonstrated that this E/I balance biomarker was normalized by acute exposure to the
NMDA receptor modulator, memantine, which has been shown to improve neurocognition in subgroups of
schizophrenia patients. These findings suggest that this novel biomarker may be used to predict therapeutic
sensitivity to memantine, and potentially other pro-cognitive interventions.
 While these preliminary results represent a compelling proof-of-concept, this novel biomarker is not yet
ready for large-scale application in prospective rehabilitation trials of pro-cognitive interventions. First, Molina
et al. (2020) is the only study to have assessed this E/I biomarker in schizophrenia patients; therefore,
replication of this finding – and extending it to Veterans with schizophrenia - is essential. Second, studies have
not yet established the stability of this biomarker, nor its suitability for use as a repeated measure in
prospective rehabilitative trials. Third, the cognitive and functional consequences of abnormal E/I balance have
not yet been determined. In two Specific Aims, this CDA-1 application seeks to address these issues by
measuring E/I balance in Veterans with schizophrenia (n=20) and in a nonpsychiatric Veteran comparison
group (n=20) recruited from VASDHS rehabilitation settings and outpatient clinics. All participants will undergo
comprehensive neurophysiologic, neurocognitive and functional assessments during two test days s...

## Key facts

- **NIH application ID:** 10189248
- **Project number:** 1IK1RX003683-01
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** JUAN MOLINA
- **Activity code:** IK1 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189248

## Citation

> US National Institutes of Health, RePORTER application 10189248, Biomarker Validation to Improve Cognitive and Psychosocial Outcomes in Veterans with Chronic Psychosis (1IK1RX003683-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10189248. Licensed CC0.

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