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Progression of Neurometabolic Dysfunction and Mechanisms of Cognitive Training in Mid- to Late-Life Schizophrenia

Award Number: R01MH139659
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Progression of Neurometabolic Dysfunction and Mechanisms of Cognitive Training in Mid- to Late-Life Schizophrenia - PROJECT SUMMARY Cognitive and visual impairments among people with schizophrenia (SZ) represent a significant mental health and healthcare cost burden. Cognitive and visual functions rely on brain energy supply and excitatory:inhibitory balance, which are altered in SZ and healthy aging. Evidence suggests the effects of aging on brain function may be prematurely advanced in schizophrenia, but whether cognition and perception decline more rapidly with age in SZ, and the neurochemical mechanisms of those changes, remains unclear. Encouragingly, both SZ and healthy older adults show improvements in functioning after cognitive training that targets cognition and perception. This proposal will test the hypothesis that glucose metabolism and excitatory glutamatergic functioning are dysregulated in schizophrenia during mid-to-late life, which contribute to cognitive and visual impairments, and may normalize in response to cognitive training. We will use 7 T MRS to quantify brain chemistry in prefrontal and occipital cortex in 81 SZ and 81 healthy controls (aged 35-79) in an accelerated longitudinal experimental design across 3 scanning sessions per person (0, 18, 30 months), plus a fourth session after cognitive training (32 months). Participants will be divided into 3 age cohorts (demographically balanced; n = 27 per cohort per group). We recently collected a large 7 T MRS data set as part of the Psychosis Human Connectome Project, which supports the feasibility of our approach. We will re-recruit participants from the previous study, which will give us additional longitudinal data. Assessing how brain chemistry changes longitudinally in mid-to-late life schizophrenia will provide critical insight into the neural basis of cognitive and visual impairments. Using cognitive training will allow us to probe the mechanisms of plasticity that support improved cognitive and visual performance in SZ and older adults. Our work will help to identify novel biomarkers for predicting individual trajectories of brain health in mid-to-late life schizophrenia, as well as brain mechanisms for future interventional work using cognitive training. These are important steps to reduce suffering and healthcare costs associated with SZ.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $719,832 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Mental Health Research Grants	000	1	9/2/2026	NEW	$719,832
														Subtotal = $719,832

Grand Total All Awards = $719,832

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Progression of Neurometabolic Dysfunction and Mechanisms of Cognitive Training in Mid- to Late-Life Schizophrenia

Award Number: R01MH139659

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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