This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: Bipolar disorder has a lifetime prevalence of approximately 1.5% in the general population. It is related to substantial morbidity and mortality, and its pathophysiology is still not known. Bipolar depression, the depressive phase of the illness, has been increasingly recognized as a major challenge in the management of bipolar patients and is the frequent cause of chronic impairment.
The specific aims of the proposed study are: (1) Investigate the presence of anatomical and neurochemical brain abnormalities in fronto-limbic brain regions involved in mood regulation in depressed bipolar type II patients; (2) Examine whether treatment with a mood stabilizer (lamotragine) has a pronounced antidepressant effect and is related to improvement or reversal of identified brain changes in bipolar type II depression; and (3) Examine whether clinical response to lamotrigine treatment is related to specific brain abnormalities in depressed bipolar type II patients. RESEARCH PLAN: The study will examine specific abnormalities in fronto-limbic brain structures involved in mood regulation in a group of depressed bipolar type II patients and healthy controls, and it will begin to investigate the effects of illness phase and treatment on identified abnormalities. We will utilize in vivo anatomical and neurochemical brain measurements with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We will conduct an in vivo investigation of brain morphology and regional levels of N-Acetyl Aspartate (NAA), a non-specific marker of neuronal viability/function, in the prefrontal cortex and medial temporal lobe. METHODS: The specific hypotheses that will be examined in this study are: (1) There are specific morphometric and neurochemical abnormalities in fronto-limbic brain regions involved in mood regulation in depressed bipolar type II patients; specifically, we predict a reduction in NAA levels in dorsolateral prefrontal cortex, and an enlargement of the amygdala, indicating impairment of these two structures, similarly to what has been described in bipolar type I patients; (2) Enlargement of amygdala, and decreased levels of NAA in dorsolateral prefrontal cortex will reverse after lamotrigine treatment; (3) Patients who respond to lamotrigine treatment will have less pronounced anatomical and neurochemical brain abnormalities at baseline compared to ones who do not respond to treatment. We will recruit 30 depressed bipolar type II subjects and 30 matched healthy controls over a 3-year period. Subjects will be diagnosed according to the DSM-IV criteria, as established in a SCID-IV interview. All patients will undergo a brain MRI/MRS scan at the time of entry in the study, and will then be treated openly with lamotrigine up to 200 mg/day for a period of 12 weeks, as monotherapy. At the end of the treatment period, another MRI/MRS scan will be completed. CLINICAL

Public Health Relevance

The study will examine the role of fronto-limbic abnormalities in mechanisms involved in bipolar type II depression and treatment response. The elucidation of involved mechanisms could begin to shed light into the specific processes underlying treatment response and refractoriness in bipolar depression. These studies have considerable potential to elucidate the pathophysiology of bipolar disorder and ultimately contribute to the development of novel and more effective treatments for this severe psychiatric illness.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR001346-25
Application #
7378201
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2006-04-01
Project End
2007-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
25
Fiscal Year
2006
Total Cost
$32,557
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
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
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
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
Marquez, Becky; Anderson, Andrea; Wing, Rena R et al. (2016) The relationship of social support with treatment adherence and weight loss in Latinos with type 2 diabetes. Obesity (Silver Spring) 24:568-75
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

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