Major depression ranks among the leading biobehavioral risk factors for cardiovascular (CV) morbidity and mortality. Research has revealed several pathways through which depression increases CV risk including health behaviors and psychosocial functioning. That depression remains a significant predictor of CV disease (CVD) after intervening to improve health behaviors and psychosocial functioning in adults with depression suggests that additional, important risk factors have yet to be identified. We have developed a conceptual model that extends previous research on depression and CV risk by considering sleep as a novel biobehavioral mediator through which depression increases CV risk. We hypothesize that sleep disturbance, including decreased sleep duration, continuity and depth and increased sleep disordered breathing contribute to the increased CV risk observed in adults with major depression. Importantly, each of these components of sleep is modifiable and may represent promising therapeutic targets for reducing the cardiovascular consequences of major depression. The proposed 5-year study will evaluate these relationships in a well-characterized cohort of 200 adults with a history of recurrent major depressive disorder (MDD) who underwent psychiatric assessments and sleep studies in our laboratory approximately 10 to 30 years ago (T1). Participants, who were medically healthy without clinical cardiovascular disease at T1, exhibited profound sleep disturbances that persisted during remission. Members of this cohort have expressed great interest in the proposed follow-up study (T2). Proposed T2 measures include follow-up psychiatric assessments and sleep studies coupled with assessment of CV risk and subclinical disease including indices of autonomic imbalance, endothelial dysfunction, preclinical atherosclerosis and the metabolic syndrome. We will also assess health behaviors, psychosocial functioning and potential confounding variables. Together, these data will provide the first test of the hypothesized paths in our conceptual model. Our primary aim is to use T1 depression and sleep data in conjunction with T2-assessed CV outcomes to evaluate whether PSG-assessed sleep disturbance attenuates the prospective relationship between depression and CV risk and subclinical disease. Our secondary aim is to evaluate both wake and sleep """"""""pathways"""""""" in the same model, using data collected at T2, including objective assessment of physical activity. The use of multiple-group structural equation models will provide the opportunity to evaluate whether relationships among depression, sleep disturbance and CV risk/subclinical disease differ by age and gender (exploratory aim). In future studies, experimental approaches will be needed to establish sleep as a causal pathway, identify the biological mechanisms through which specific components of disturbed sleep in depressed individuals increase CV risk, and develop evidence-based sleep interventions to prevent or attenuate the cardiovascular consequences of major depression.

Public Health Relevance

The proposed study will be the first to evaluate sleep as a novel pathway through which depression increases cardiovascular disease risk, morbidity and mortality. Insights into the role of sleep disturbance in the link between major depression and cardiovascular disease is essential to our understanding of the pathophysiology of this prevalent and costly disease. Because sleep represents a modifiable pathway through which depression increases cardiovascular disease risk, it holds promise for the design and implementation of effective, evidence-based interventions to prevent and/or treat the cardiovascular consequences of major depression.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL104607-04
Application #
8479138
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Stoney, Catherine
Project Start
2010-09-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$647,571
Indirect Cost
$190,020
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Hall, Martica H; Brindle, Ryan C; Buysse, Daniel J (2018) Sleep and cardiovascular disease: Emerging opportunities for psychology. Am Psychol 73:994-1006
Smagula, Stephen F; Krafty, Robert T; Thayer, Julian F et al. (2018) Rest-activity rhythm profiles associated with manic-hypomanic and depressive symptoms. J Psychiatr Res 102:238-244
Brindle, Ryan C; Duggan, Katherine A; Cribbet, Matthew R et al. (2018) Cardiovascular Stress Reactivity and Carotid Intima-Media Thickness: The Buffering Role of Slow-Wave Sleep. Psychosom Med 80:301-306
Brindle, Ryan C; Cribbet, Matthew R; Samuelsson, Laura B et al. (2018) The Relationship Between Childhood Trauma and Poor Sleep Health in Adulthood. Psychosom Med 80:200-207
Bruce, Scott A; Hall, Martica H; Buysse, Daniel J et al. (2018) Conditional adaptive Bayesian spectral analysis of nonstationary biomedical time series. Biometrics 74:260-269
Hall, Martica H; Mulukutla, Suresh; Kline, Christopher E et al. (2017) Objective Sleep Duration Is Prospectively Associated With Endothelial Health. Sleep 40:
Kline, Christopher E; Krafty, Robert T; Mulukutla, Suresh et al. (2017) Associations of sedentary time and moderate-vigorous physical activity with sleep-disordered breathing and polysomnographic sleep in community-dwelling adults. Sleep Breath 21:427-434
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Samuelsson, Laura B; Hall, Martica H; McLean, Shakir et al. (2015) Validation of Biomarkers of CVD Risk from Dried Blood Spots in Community-Based Research: Methodologies and Study-Specific Serum Equivalencies. Biodemography Soc Biol 61:285-97

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