This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.OBJECTIVE: This study will examine the existence of particular in vivo neurochemical and morphometric brain abnormalities in unipolar mood disorder subjects, and their potential involvement in the pathophysiology of this illness. We will also examine potential in vivo brain correlates of prior suicidal behavior in this patient population.RESEARCH PLAN: We will investigate regional brain myo-inositol and platelet membrane phosphoinositide levels in 30 unmedicated unipolar patients (15 depressed and 15 in the remitted state) and 30 age, sex, educational level, and race-matched healthy controls. In addition to that, we will examine brain morphometry of key brain regions involved in mood regulation, to attempt to determine their relationship with illness symptoms. We will also examine brain correlates of suicide behavior by comparing patients with prior suicide attempts and the ones without such attempts.METHODS: All subjects undergo a 1.5T proton MIR/MRS brain scan, which allows the quantitation of myoinositol in 8cc brain voxels located in the frontal cortex, medial temporal lobe, and basal ganglia. At the same time, subjects provide a blood sample for platelet determination of membrane phosphoinositides, which is done with two-dimensional thin layer chromatography, followed by scanning laser densitometry. This research holds substantial promise to contribute to a better understanding of the biochemical brain dysfunction underlying mood disorders, and ultimately guide future efforts towards the development of new treatments for these conditions.CLINICAL

Public Health Relevance

This study will allow examination of involvement of abnormalities in the phosphoinositol (PI) pathway in pathophysiology of depression and mood disorders. It will also allow examination of anatomical involvement of specific brain regions participating in mood regulation in the pathophysiology of mood disorders. It could also possibly aid in development of new ways to identify depressed unipolar patients at high risk for suicide.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR001346-26
Application #
7627521
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2007-04-01
Project End
2008-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
26
Fiscal Year
2007
Total Cost
$46,131
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Kawaguchi-Suzuki, Marina; Cusi, Kenneth; Bril, Fernando et al. (2018) A Genetic Score Associates With Pioglitazone Response in Patients With Non-alcoholic Steatohepatitis. Front Pharmacol 9:752
Hayden, Kathleen M; Baker, Laura D; Bray, George et al. (2018) Long-term impact of intensive lifestyle intervention on cognitive function assessed with the National Institutes of Health Toolbox: The Look AHEAD study. Alzheimers Dement (Amst) 10:41-48
Unick, Jessica L; Gaussoin, Sarah A; Hill, James O et al. (2017) Objectively Assessed Physical Activity and Weight Loss Maintenance among Individuals Enrolled in a Lifestyle Intervention. Obesity (Silver Spring) 25:1903-1909
Kawaguchi-Suzuki, M; Bril, F; Kalavalapalli, S et al. (2017) Concentration-dependent response to pioglitazone in nonalcoholic steatohepatitis. Aliment Pharmacol Ther 46:56-61
Johnson, Karen C; Bray, George A; Cheskin, Lawrence J et al. (2017) The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial. J Bone Miner Res 32:2278-2287
Lorenzo, Carlos; Festa, Andreas; Hanley, Anthony J et al. (2017) Novel Protein Glycan-Derived Markers of Systemic Inflammation and C-Reactive Protein in Relation to Glycemia, Insulin Resistance, and Insulin Secretion. Diabetes Care 40:375-382
Beavers, Kristen M; Leng, Iris; Rapp, Stephen R et al. (2017) Effects of Longitudinal Glucose Exposure on Cognitive and Physical Function: Results from the Action for Health in Diabetes Movement and Memory Study. J Am Geriatr Soc 65:137-145
Chao, Ariana M; Wadden, Thomas A; Gorin, Amy A et al. (2017) Binge Eating and Weight Loss Outcomes in Individuals with Type 2 Diabetes: 4-Year Results from the Look AHEAD Study. Obesity (Silver Spring) 25:1830-1837
Williams, Robert C; Elston, Robert C; Kumar, Pankaj et al. (2016) Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND). BMC Genomics 17:325
Belalcazar, L Maria; Papandonatos, George D; Erar, Bahar et al. (2016) Lifestyle Intervention for Weight Loss and Cardiometabolic Changes in the Setting of Glucokinase Regulatory Protein Inhibition: Glucokinase Regulatory Protein-Leu446Pro Variant in Look AHEAD. Circ Cardiovasc Genet 9:71-8

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