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Translational Approach to Studying miRNA functions in sACC and amygdala in patients with BPD

Award Number: R01MH132806
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Translational Approach to Studying miRNA functions in sACC and amygdala in patients with BPD - Abstract: Bipolar disorder (BPD) is a severe mental disorder with a significant burden on public health. MiRNAs are highly expressed in the brain and have been shown by us and others to play a role in the neuropathology of BPD and other psychiatric disorders. However, to date, all published postmortem brain miRNA expression studies of BPD have been hampered by small sample sizes, older detection platforms, and a lack of comprehensive data integration with other genomic resources. To address these limitations, we propose a translational approach that will apply miRNA sequencing in the amygdala and subgenual cingulate anterior cortex (sAAC) in 150 patients diagnosed with bipolar disorder and matched 150 neurotypical controls, followed by a replication study in an independent sample of 100 matched case/control sample. Our aims are designed to take full advantage of this large and exceptionally well clinically characterized sample. With our large discovery and replication samples, we are powered to identify moderate to small effect sizes typically observed in neuropsychiatric disorders. By leveraging other pre-existing genomic datasets (i.e., GWAS data and RNA-seq) generated in our sample, we will apply a state-of-art series of bioinformatic and statistical approaches for the comprehensive integration of these genomic data. This integration will lead to the generation of specific and testable hypotheses. As an example, integrating the miRNA- seq data with GWAS of BPD (from the Psychiatric Genomics Consortium) will reveal the genetic mechanisms by which genome-wide significant risk variants contribute to the etiology of bipolar disorder, e.g., variants affecting miRNA expression between BPD cases and controls. Integrating the miRNA-Seq and RNA-Seq data will identify miRNA gene targets with important functions in the etiology of bipolar disorder. Finally, we will identify a set of high confidence risk miRNA of BPD (i.e., miRNAs with convergent evidence from the discovery, eQTL, bioinformatic, and replication analyses) and deliver these in mice models to delineate the disease-specific functions and roles these miRNA play in BPD neuropathology. In summary, the neurobiological mechanisms by which polymorphisms associated with BPD increase the risk for bipolar disorder are unknown. We hypothesize that one of the mechanisms contributing to the neuropathology of BPD is the ability of risk BPD variants to affect miRNA expression. Using such large discovery and replication brain samples of BPD, we will identify miRNA, whose expression is robustly associated with bipolar disorder and under the control of risk variants for BPD and further validate their disease functions by testing their impact on behavioral measures in mice models.


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 = $743,673 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Mental Health Research Grants	000	3	7/6/2026	NON-COMPETING CONTINUATION	$743,673
														Subtotal = $743,673

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Mental Health Research Grants	000	2	3/5/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $819,401 )
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Mental Health Research Grants	001	2	7/22/2024	NON-COMPETING CONTINUATION	$81,941
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Mental Health Research Grants	000	2	3/19/2024	NON-COMPETING CONTINUATION	$737,460
														Subtotal = $819,401

Issue Date FY: 2023 ( Subtotal = $631,494 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Mental Health Research Grants	000	1	4/19/2023	NEW	$631,494
														Subtotal = $631,494

Grand Total All Awards = $2,194,568

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Translational Approach to Studying miRNA functions in sACC and amygdala in patients with BPD

Award Number: R01MH132806

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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