Epidemiologic and clinical studies have established that Major Depression (MD) often co-occurs with medical conditions in later life, including metabolic disorders such as Type 2 Diabetes Mellitus (hereafter referred to as 'Diabetes'). It is now acknowledged that the inter-relationship between MD and Diabetes is likely bi-directional. Indeed, there is consistent evidence from population-based cohort studies that MD is associated with increased risk of and mortality from Diabetes and cardiovascular disease. However, prospective studies cannot definitively distinguish whether MD is a unique risk factor for metabolic disorders, or if this phenomenon is due to a common factor shared by both MD and Diabetes such as genetic liability, environmental stress, or systemic physiologic deregulation. Functional genomics, particularly assessment of gene expression, offer a novel means of specifying how environmental exposures intersect with genetic liability to influence physiology. The broad objective of this Career Development Award (K01) is to investigate the etiologic relationships between co-occurring MD and Diabetes, in particular the structural and relative contributions of genetic and environmental sources of risk. This research utilizes complementary approaches to investigating the aims below: first, the broad genetic and environmental pathways underlying this comorbidity will be examined using latent variable twin modeling;second, gene expression arrays will be used to examine specific biological pathways by which depressive symptoms influence Diabetes risk.
The specific aims of the research plan are to: 1) evaluate environmental and genetic contributions, and their interaction, of the relationship between MD and Diabetes in later adulthood;2) investigate the behavioral pathways linking MD and Diabetes while accounting for shared genetic liability;and 3) examine the relationship between depressive symptoms and expression of immune-related genes. The candidate will receive training in responsible conduct of research, genetic epidemiology, and functional genomics. The candidate proposes to implement this research plan during a period of closely mentored training with experts in psychiatry, immunology, functional genomics, epidemiology, and biostatistics. The proposed training plan will promote her transition to independence as an epidemiologist focused on exploring an integrative model of the psychological, behavioral, biological, and genetic aspects of mental health. The research plan addresses the intersection of two common and debilitating health conditions, Major Depression and Diabetes, that are leading sources of healthcare costs and public health burden in the US and globally. The public health significance of this research centers on understanding the etiologic relationships between mental and physical health in order to develop comprehensive programs to improve the health of persons with psychiatric disorders.

Public Health Relevance

The goal of this application is to investigate the etiologic nature of co-occurring MD and Diabetes using complementary data from two population-based cohorts and a genetically informative twin study. The aims are to: 1) evaluate environmental and genetic contributions, and their interaction, of the relationship between MD and Diabetes in later adulthood;2) investigate the behavioral pathways linking MD and Diabetes while accounting for shared genetic liability;and 3) examine the influence of depressive symptoms on expression of immune-related genes. The significance of this research centers on understanding the etiologic relationships between mental and physical health to improve the health of persons with psychiatric disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH093642-03
Application #
8699522
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Chavez, Mark
Project Start
2012-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Kendler, Kenneth S; Ohlsson, Henrik; Mezuk, Briana et al. (2016) A Swedish National Prospective and Co-relative Study of School Achievement at Age 16, and Risk for Schizophrenia, Other Nonaffective Psychosis, and Bipolar Illness. Schizophr Bull 42:77-86
Mezuk, Briana; Li, Xinjun; Cederin, Klas et al. (2016) Beyond Access: Characteristics of the Food Environment and Risk of Diabetes. Am J Epidemiol 183:1129-37
Jäggi, Lena J; Mezuk, Briana; Watkins, Daphne C et al. (2016) The Relationship between Trauma, Arrest, and Incarceration History among Black Americans: Findings from the National Survey of American Life. Soc Ment Health 6:187-206
Cha, Susan; Masho, Saba W; Mezuk, Briana (2016) Age of Sexual Debut and Cannabis Use in the United States. Subst Use Misuse 51:439-48
Concha, Jeannie Belinda; Mayer, Sallie D; Mezuk, Briana R et al. (2016) Diabetes Causation Beliefs Among Spanish-Speaking Patients. Diabetes Educ 42:116-25
Needham, B L; Mezuk, B; Bareis, N et al. (2015) Depression, anxiety and telomere length in young adults: evidence from the National Health and Nutrition Examination Survey. Mol Psychiatry 20:520-8
Robinson, Whitney R; Kershaw, Kiarri N; Mezuk, Briana et al. (2015) Coming unmoored: disproportionate increases in obesity prevalence among young, disadvantaged white women. Obesity (Silver Spring) 23:213-9
Brown, Monique J; Perera, Robert A; Masho, Saba W et al. (2015) Adverse childhood experiences and intimate partner aggression in the US: sex differences and similarities in psychosocial mediation. Soc Sci Med 131:48-57
Mezuk, Briana; Li, Xinjun; Cederin, Klas et al. (2015) Ethnic enclaves and risk of psychiatric disorders among first- and second-generation immigrants in Sweden. Soc Psychiatry Psychiatr Epidemiol 50:1713-22
Ratliff, Scott; Mezuk, Briana (2015) Depressive symptoms, psychiatric medication use, and risk of type 2 diabetes: results from the Health and Retirement Study. Gen Hosp Psychiatry 37:420-6

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