Date of Award

January 2017

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Nihar Desai

Abstract

Introduction

Psoriasis is a chronic inflammatory disorder associated with both cardiovascular disease and mood disorders such as depression and anxiety. Multiple behavioral and physiological processes link depression, psoriasis and atherosclerosis, but inflammation is a major player implicated in the pathogenesis of all three. Psoriasis is associated with vascular inflammation, measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and an increased risk of myocardial infarction. Vascular inflammation by FDG PET/CT predicts cardiovascular risk and outcomes. Studies have also shown that patients with psoriasis are more likely to suffer from comorbid depression and anxiety. However, whether these comorbidities may accelerate the development of cardiovascular disease in psoriasis is not well-characterized.

Hypothesis

Our primary hypothesis is that aortic vascular inflammation and coronary plaque burden will be increased in patients with psoriasis who have depression when compared to psoriasis patients who do not. In a follow-up study we hypothesize that metabolic activity in the anatomic location of the amygdala will correlate with increased vascular inflammation and decreased vascular function.

Methods

An ongoing psoriasis study cohort was chosen for the patient population. Patients who reported a history of depression (n=36) on survey were matched by age and sex to patients who reported no history of psychiatric illness (n=36). FDG PET/CT scans were used to assess vascular inflammation. From these scans, standardized uptake values were calculated by analyzing axial slices of the aorta. Target-to-background ratios were then calculated to standardize for background luminal FDG uptake. Coronary computed tomography angiography scans were analyzed in order to determine coronary plaque composition and to quantify plaque burden. Multivariate linear regression analyses were performed to understand the potential effect of psychiatric diagnoses on aortic vascular inflammation and coronary plaque burden. Traditional cardiovascular risk factors were adjusted for (standardized β reported). In a follow-up study, metabolic activity of the amygdala was quantified via analysis of FDG uptake in the anatomic location of the amygdala. These uptake values were divided by FDG uptake in the adjacent ipsilateral temporal lobe for standardization. Target-to-background ratios were then used to quantify amygdala activity. Vascular function was studied via aortic distensibility. Using phase contrast MRI scans throughout the duration of one cardiac cycle, axial slices of the aorta were analyzed to calculate aortic distensibility.

Results

Aortic vascular inflammation and coronary plaque burden were increased in psoriasis patients with comorbid depression as compared to those without. After adjustment for Framingham Risk Score, vascular inflammation (β=0.26, p=0.02), total plaque burden (β=0.17, p=0.03), and non-calcified plaque burden (β=0.17, p=0.03) associated with comorbid depression. In a subsequent study, patients with comorbid depression and/or anxiety had higher left amygdala activity. In unadjusted analyses vascular inflammation significantly associated with amygdala activity, although this relationship did not retain significance after adjustment for traditional cardiovascular risk. Aortic distensibility was significantly and inversely associated with left amygdala activity both in unadjusted analyses and after adjustment for traditional cardiovascular risk.

Conclusions

Patients with psoriasis who suffer from comorbid depression have greater burden of subclinical cardiovascular disease. Furthermore, vascular function is reduced in these patients and correlates with the degree of activity in the amygdala, a region of the brain that plays an important role in the modulation of stress. Targeted assessment of psychological stress and mood disorders in psoriasis patients may be warranted for further cardiovascular risk reduction in this high-risk population.

Comments

This is an Open Access Thesis.

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