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Laminar dissection of cortical human brain gene expression in neuropsychiatric disorders

Award Number: R01MH126393
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/23/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Laminar dissection of cortical human brain gene expression in neuropsychiatric disorders - Project Summary/Abstract The DLPFC is a true six layered neocortex, and neurons in different cortical layers show distinct expression patterns, morphology, physiology and patterns of connectivity. Converging evidence suggests that impairments in the formation or maintenance of synapses may be involved in schizophrenia and other neuropsychiatric disorders. Studies in the postmortem brains of subjects have pointed to specific cell types and revealed differences in neuronal and synaptic structure that are localized to specific layers, suggesting that genetic risk for schizophrenia may manifest with laminar specificity. Given the close relationship between brain structure and function, precisely assigning gene expression to the spatial coordinates of individual cell populations within this cortical cytoarchitecture would significantly advance our understanding of how dysregulation in these areas contributes to debilitating neuropsychiatric disorders. In this application, we propose to generate detailed spatial transcriptomics maps of the human DLPFC in patients with schizophrenia (SCZD), bipolar (BPD), major depressive (MDD) and autism spectrum (ASD) disorders, and contrast these laminar expression patterns to those derived from matched neurotypical controls (CONT). We will use the 10x Genomics Visium platform, which combines transcriptome-wide RNA sequencing with detailed high-resolution histology and immunofluorescence imaging, to generate these spatial transcriptomics profiles. We will combine these topographic and cell type-specific maps to implicate layer- and cell type-specific populations in psychiatric disorder genetic risk and illness state that will be validated using complementary quantitative in situ hybridization techniques. These layer-specific and cell type-specific expression profiles can refine the molecular causes and consequences of debilitating neuropsychiatric disorders that can be targeted for prevention and treatment.


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: 2025 ( Subtotal = $677,158 )
2025	2025	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	5	4/15/2025	NON-COMPETING CONTINUATION	$677,158
														Subtotal = $677,158

Issue Date FY: 2024 ( Subtotal = $821,142 )
2024	2024	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	001	4	8/16/2024	NON-COMPETING CONTINUATION	$82,114
2024	2024	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	4	4/4/2024	NON-COMPETING CONTINUATION	$739,028
														Subtotal = $821,142

Issue Date FY: 2023 ( Subtotal = $770,300 )
2023	2023	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	3	3/22/2023	NON-COMPETING CONTINUATION	$770,300
														Subtotal = $770,300

Issue Date FY: 2022 ( Subtotal = $802,692 )
2022	2022	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	2	4/1/2022	NON-COMPETING CONTINUATION	$802,692
														Subtotal = $802,692

Issue Date FY: 2021 ( Subtotal = $844,939 )
2021	2021	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	6/23/2021	NEW	$844,939
														Subtotal = $844,939

Grand Total All Awards = $3,916,231

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Laminar dissection of cortical human brain gene expression in neuropsychiatric disorders

Award Number: R01MH126393

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/23/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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