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 #
5K01MH093642-02
Application #
8517191
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
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$173,973
Indirect Cost
$12,776
Name
Virginia Commonwealth University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Moscati, Arden; Mezuk, Briana (2014) Losing faith and finding religion: religiosity over the life course and substance use and abuse. Drug Alcohol Depend 136:127-34
Agyemang, Amma A; Mezuk, Briana; Perrin, Paul et al. (2014) Quality of depression treatment in Black Americans with major depression and comorbid medical illness. Gen Hosp Psychiatry 36:431-6
Savage, Jeanne E; Mezuk, Briana (2014) Psychosocial and contextual determinants of alcohol and drug use disorders in the National Latino and Asian American Study. Drug Alcohol Depend 139:71-8
Lohman, Matthew; Dumenci, Levent; Mezuk, Briana (2014) Sex differences in the construct overlap of frailty and depression: evidence from the Health and Retirement Study. J Am Geriatr Soc 62:500-5
Mezuk, Briana; Rock, Andrew; Lohman, Matthew C et al. (2014) Suicide risk in long-term care facilities: a systematic review. Int J Geriatr Psychiatry 29:1198-211
Choi, Moon; Lohman, Matthew C; Mezuk, Briana (2014) Trajectories of cognitive decline by driving mobility: evidence from the Health and Retirement Study. Int J Geriatr Psychiatry 29:447-53
Do, Elizabeth K; Mezuk, Briana (2013) Comorbidity between hypomania and substance use disorders. J Affect Disord 150:974-80
Mezuk, Briana; Chaikiat, Asa; Li, Xinjun et al. (2013) Depression, neighborhood deprivation and risk of type 2 diabetes. Health Place 23:63-9
Mezuk, Briana; Chen, Yiping; Yu, Canqing et al. (2013) Depression, anxiety, and prevalent diabetes in the Chinese population: findings from the China Kadoorie Biobank of 0.5 million people. J Psychosom Res 75:511-7
Mezuk, Briana; Abdou, Cleopatra M; Hudson, Darrell et al. (2013) "White Box" Epidemiology and the Social Neuroscience of Health Behaviors: The Environmental Affordances Model. Soc Ment Health 3:

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