# Enhancing Cognitive Training Through Exercise Following a First Schizophrenia Episode

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $417,844

## Abstract

ABSTRACT
This R01 application involves a confirmatory efficacy clinical trial of our innovative treatment approach to
improving cognition in schizophrenia, using an experimental therapeutic design that NIMH has advocated. Our
intervention approach combines neurotrophin-releasing aerobic exercise training with neuroplasticity-based
cognitive training to enhance the impact of cognitive training on cognition and functional outcome. Both
cognitive training and exercise address the NIMH strategic research priorities for creating innovative
interventions that can be “disseminated broadly” and “readily taught to the existing workforce with minimal
cost.” Cognitive remediation and physical exercise have each been shown separately to have promise for
improving cognitive deficits in schizophrenia, but used separately yield moderate effects in chronic
schizophrenia patients. We will use brain-derived neurotrophic factor (BDNF) as our target and cognition and
functional outcome as our clinical outcomes. We hypothesize that the increases in BDNF associated with
regular aerobic exercise provide a platform which allows neuroplasticity-based cognitive training to enhance
cognition to a greater degree than is typically observed in studies of cognitive training alone. We hypothesize
that combining physical exercise with cognitive training will produce larger cognitive and functional
improvements, relative to cognitive training alone. This confirmatory efficacy clinical trial is guided by evidence
from our current R34 pilot randomized controlled trial comparing the combined treatment with cognitive training
without physical exercise. We find compelling evidence of BDNF target engagement, differential improvement
in cognition and functional outcome, and prediction of later outcome from initial BDNF gain that strongly
supports the movement to a fully powered confirmatory efficacy clinical trial. Cognitive deficits in persons with
schizophrenia present an enormous challenge to successful return to functioning in the community. We target
the period shortly after a first episode of schizophrenia to maximize the generalization of cognitive
improvement to real-world functional outcome, before chronic disability is established. The cognitive training
plus aerobic exercise intervention has the potential to examine a hypothesized mechanism of action and to
make a meaningful difference in the lives of individuals with severe mental illness.

## Key facts

- **NIH application ID:** 10519768
- **Project number:** 3R01MH110544-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** KEITH H NUECHTERLEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $417,844
- **Award type:** 3
- **Project period:** 2016-09-02 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519768

## Citation

> US National Institutes of Health, RePORTER application 10519768, Enhancing Cognitive Training Through Exercise Following a First Schizophrenia Episode (3R01MH110544-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10519768. Licensed CC0.

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