Sleep disturbance and autonomic dysregulation as pathways of mortality and cardiovascular risk in depression Public
Huang, Minxuan (Fall 2020)
Abstract
Depression is a prevalent psychiatric condition, and remains a risk factor for adverse health outcomes, including mortality and cardiovascular disease (CVD). However, little is known about the pathophysiology underlying depression and its associated consequences. Sleep disturbance is a modifiable behavior that is a common symptom of depression; autonomic dysregulation has been linked to depression. Both factors independently contribute to higher risk of mortality and CVD. The objective was to elucidate the complex roles of sleep disturbance and autonomic dysregulation on the pathways linking depression and adverse outcomes, using a co-twin control design. This dissertation leveraged data from the Emory Twin Study, which included 283 pairs (n=566) from members of the Vietnam Era Twin Registry.
In Aim 1, we conducted a cross-sectional evaluation of the association of depressive symptoms, assessed by the Beck Depression Inventory-II (BDI), with sleep disturbance, assessed by in-lab polysomnography, at-home actigraphy, and the self-rated Pittsburgh Sleep Quality Index. We found that depression was associated with longer rapid eye movement sleep disruption, sleep fragmentation and variability. Depression was consistently not associated with sleep architecture or sleep-disordered breathing.
In Aim 2, we evaluated the temporal relationships between sleep and autonomic dysregulation indexed by heart rate variability (HRV). We found that the associations of daytime HRV with sleep stages, cumulative hypoxic burden and sleep continuity measures were bidirectional. Autonomic function during wakefulness and sleep disturbance are closely interrelated and their influence on each other may extend beyond 24 hours.
In Aim 3, we assessed the prognostic implications of baseline HRV and depression with adverse outcomes during 12-year follow-up. We found that depression and reduced HRV at baseline were associated with higher risk of all-cause mortality and CVD during follow-up.
The findings of this dissertation extend the existing literature by providing substantial evidence that depression, sleep disturbance and autonomic dysregulation are closely interrelated, and they together contribute to a higher risk of adverse outcomes. Our results contribute to clarify the link between depression and its outcomes, and help inform future research on strategies targeting sleep and HRV in lowering mortality and cardiovascular risk in depressed individuals.
Table of Contents
CHAPTER 1: INTRODUCTION
1.1 Background
1.2 Study Motivation
1.3 Objective and Specific Aims
1.4 Data Source
1.5 Public Health Importance
CHAPTER 2: BACKGROUND AND LITERATURE REVIEW
2.1 Depression and Adverse Health Outcomes
2.2 Depression and Sleep Disturbance
2.3 Depression and Autonomic Dysregulation
2.4. Sleep Disturbance and Autonomic Dysregulation
2.5 Sleep Disturbance and Adverse Health Outcomes
2.6 Autonomic Dysregulation and Adverse Health Outcomes
2.7 Preliminary Work
CHAPTER 3: METHODS
3.1 Data Source
3.2 Measurements of Depression
3.3. Measurements of Sleep Disturbance
3.4 Measurements of Autonomic Dysregulation
3.5 Measurements of Adverse Health Outcomes
3.6 Other Measurements
3.7 Data Analysis Plan
CHAPTER 4: AIM 1: THE ASSOCIATION BETWEEN DEPRESSIVE SYMPTOMS AND SLEEP DISTURBANCE
4.1 Abstract
4.2 Introduction
4.3 Methods
4.4 Results
4.5 Discussion
4.6 Conclusions
CHAPTER 5: AIM 2: THE TEMPORAL RELATIONSHIPS BETWEEN SLEEP DISTURBANCE AND AUTONOMIC DYSREGULATION
5.1 Abstract
5.2 Introduction
5.3 Methods
5.4 Results
5.5 Discussion
5.6 Conclusions
CHAPTER 6: AIM 3: DEPRESSION AND AUTONOMIC DYSREGULATION AND TIME TO ADVERSE HEALTH OUTCOMES
6.1 Abstract
6.2 Introduction
6.3 Methods
6.4 Results
6.5 Discussion
6.6 Conclusions
CHAPTER 7: SUMMARY AND FUTURE DIRECTIONS
7.1 Summary
7.2 Strengths
7.3 Limitations
7.4 Public Health Impact
7.5 Future Directions
REFERENCES
About this Dissertation
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