Document Type


Date of Degree

Spring 2016

Degree Name

PhD (Doctor of Philosophy)

Degree In


First Advisor

Fiedorowicz, Jess

First Committee Member

Robinson, Jennifer G

Second Committee Member

Snetselaar, Linda G

Third Committee Member

Ramirez, Marizen R

Fourth Committee Member

Carnahan, Ryan M


The purpose of this study was to resolve a critical gap in depression literature through assessment of the temporal relationship between depression and low LDL.

A systematic review and meta-analysis was conducted to investigate the overall cross-sectional association between serum LDL and depression. Inconsistent findings suggest that more work must be done to clarify the link between LDL and depression.

Next, Cox regression was used to explore the association between LDL and the subsequent onset of depressive symptoms within a subset of the Women’s Health Initiative cohort and evaluate the potential for effect modification by lipid-lowering medication use. This study provides evidence toward an association between low LDL and the subsequent onset of depressive symptoms, with increased risk confined to LDL below 100 mg/dL. Elevated risk was not associated with lipid-lowering medication use.

The final study examined the differences in the magnitude and direction of change in serum LDL levels among individuals experiencing new-onset depression, and examines the potential for physical activity, energy intake, and total body weight to mediate the depression-LDL relationship. This study provides no evidence of an association between depression and subsequent serum LDL changes.

Altogether, this data suggests that LDL that is below 100 mg/dL without the use of lipid-lowering medication may predispose individuals to a greater risk of depression, and also suggests that low LDL is not likely a state brought about by physiological or behavioral changes following the onset of depression.

Public Abstract

Depression is an important public health issue because it is associated, particularly among women and older adults, with substantial declines in quality of life and physical health and increased risk of disability and death. A number of studies have noted a link between low LDL and depression. However, there is still the question of what comes first – whether low LDL leads to depression or depression leads to low LDL.

To answer this question, this study first looked at low LDL and later risk of developing depressive symptoms and found that women with very low LDL, below 100 mg/dL were at higher risk. Interestingly, this was only seen in women who were not using lipid-lowering medications.

This study next looked at whether LDL levels change appreciably following the onset of depressive symptoms and found no difference between people with and without depressive symptoms.

Overall, this study suggests that women with LDL below 100 mg/dL without the use of lipid-lowering medications could be at risk for depression. LDL levels do not appear to change more or less-so in people with depressive symptoms than in people without.


Biomarkers, Cholesterol, Depression, LDL, Lipids, WHI


x, 171 pages


Includes bibliographical references (pages 119-151).


Copyright © 2016 Jane Elizabeth Persons