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ORGANISMAL, CELLULAR, AND GENETIC NETWORKS IN ANXIETY AND DEPRESSION

Award Number: R01MH077251
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/03/2007
PERIOD OF PERFORMANCE END DATE: 03/31/2013

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ORGANISMAL, CELLULAR, AND GENETIC NETWORKS IN ANXIETY AND DEPRESSION - Depression and anxiety are serious disorders that contribute to both individual disability and high economic burden. There are a broad spectrum of symptoms, diagnoses and treatments for both, and a wide range of factors that may contribute to episodes of disease. Animal models have been extensively used to try and delineate the genes involved, the confounding environmental factors, and validation of drug treatments for both anxiety and depression. Our long term goal is to define new genetic components and biochemical interactions that are key to the development of anxiety and depression. The overall hypothesis is that we can identify genetic components that contribute to disease states, or in fact treatments, of anxiety and depression, by using multiple inbred mouse strains. We have recently developed new methods to define associations between haplotype and phenotype: in silico quantitative trait loci (QTLs). The underlying prerequisite for this approach is that the inbred mouse strains show marked phenotypic differences and multiple studies have shown this to be the case. Based on these observations we propose to measure behavioral differences, levels of relevant biochemical markers, and whole-genome gene expression levels in appropriate tissues across thirty inbred mouse strains. These phenotypic data will enable a comprehensive characterization of depression and anxiety through genetic association studies on biochemical, cellular, and behavioral levels. Furthermore, our findings in mouse models will be translated to human disease relevance through candidate gene sequencing and pharmacogenomic studies. The specific aims are: 1) Identify QTL associated with behavioral differences in multiple inbred strains. We will collect data for seven behavioral assays shown to measure aspects of anxiety and depression 2) Develop multiplexed sets of assays for biochemical markers for QTL mapping studies. Up to 15 multiplexed biochemical markers associated with anxious or depressive phenotypes will be developed for measurement of basal analyte levels. 3) Characterize genetic regulatory pathways using gene expression profiling in relevant tissues over multiple strains. Whole genome gene-expression analysis will be performed across strains for seven tissues. 4) Assess the relevance of inbred strain mouse models using candidate gene sequencing and pharmacogenomic profiling. Candidate genes identified from the multi-phenotype genetic analysis of mouse strains will be tested for polymorphisms that could be associated with disease. In addition, a drug fluoxetine, will be administered to mice to modulate basal level phenotypic measurements to track perturbations at the biochemical, genetic and organismal level.


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: 2012 ( Subtotal = $70,028 )
2012	2012	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	5	4/3/2012	SUPPLEMENT FOR EXPANSION	$70,028
														Subtotal = $70,028

Issue Date FY: 2011 ( Subtotal = $310,157 )
2011	2011	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	5	8/8/2011	NON-COMPETING CONTINUATION	$28,196
2011	2011	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	5	3/30/2011	NON-COMPETING CONTINUATION	$281,961
														Subtotal = $310,157

Issue Date FY: 2010 ( Subtotal = $313,325 )
2010	2010	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	4	4/15/2010	NON-COMPETING CONTINUATION	$313,325
														Subtotal = $313,325

Issue Date FY: 2009 ( Subtotal = $313,097 )
2009	2009	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	3	4/30/2009	NON-COMPETING CONTINUATION	$313,097
2009	2007	NOVARTIS INSTITUTE FOR FUNCTIONAL GENOMICS INC	10675 JOHN JAY HOPKINS DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Mental Health Research Grants	000	1	11/27/2008	NEW	$0
														Subtotal = $313,097

Issue Date FY: 2008 ( Subtotal = $312,342 )
2008	2008	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	2	8/26/2008	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$312,342
														Subtotal = $312,342

Issue Date FY: 2007 ( Subtotal = $318,750 )
2007	2007	GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION	10675 JOHN JAY HOPKINS DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Mental Health Research Grants	000	1	7/3/2007	NEW	$318,750
														Subtotal = $318,750

Grand Total All Awards = $1,637,699

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ORGANISMAL, CELLULAR, AND GENETIC NETWORKS IN ANXIETY AND DEPRESSION

Award Number: R01MH077251

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/03/2007

PERIOD OF PERFORMANCE END DATE: 03/31/2013

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