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Blood-Brain Barrier Leakiness and Inflammation in Schizophrenia: Implications for Dopamine Alterations

Award Number: R01MH143963
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/24/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Blood-Brain Barrier Leakiness and Inflammation in Schizophrenia: Implications for Dopamine Alterations - Project Summary Schizophrenia is a severe chronic mental illness characterized by both dopamine dysregulation and neuroinflammation known to alter neural function. Neuroinflammation leads to a leaky blood-brain barrier (BBB), and damages dopamine neurons. By studying midbrain tissue using single-cell RNA sequencing, we can identify the damaging molecular communication pathways that resident immune cells and invading immune cells use to disrupt brain homeostasis. We will determine how endothelial cells are transcriptionally and morphologically changed during brain inflammation, which will open new avenues to support strengthening the BBB as a treatment in schizophrenia. We will focus on the inflammatory environment in the schizophrenia midbrain, where we have discovered elevated cytokine and complement expression along with gliosis and macrophage infiltration. Our study will examine multiple related inflammatory pathways that mediate neuronal damage and assess whether the transcriptional profile, number, or size of dopamine neurons differs with inflammation and schizophrenia diagnosis. We will determine and map the key molecular and cellular changes underpinning a leaky BBB in proximity to dopamine neurons in the midbrain of people with schizophrenia. Additionally, we will identify serum biomarkers that distinguish high and low inflammatory states and correlate with leaky BBB status in the midbrain by linking central (brain) and peripheral measures (blood) using machine learning. This will allow the field to prioritize blood biomarkers that can be used to identify those most likely to benefit from anti-inflammatory and BBB treatments and to track potential benefits of treatment over time. Ultimately, this research will deepen our understanding of schizophrenia neuropathology and contribute to the development of novel therapies aimed at inflammatory changes to the BBB.


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 = $807,460 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Mental Health Research Grants	000	1	7/28/2026	NEW	$807,460
														Subtotal = $807,460

Grand Total All Awards = $807,460

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Blood-Brain Barrier Leakiness and Inflammation in Schizophrenia: Implications for Dopamine Alterations

Award Number: R01MH143963

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/24/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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