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Association Between BDNF DNA Methylation and Depression and Anxiety in Postmenopausal Individuals with Breast Cancer

Kirkpatrick Heimke, Kaitlin (2022) Association Between BDNF DNA Methylation and Depression and Anxiety in Postmenopausal Individuals with Breast Cancer. Master Essay, University of Pittsburgh.

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Background: Breast cancer is the second most diagnosed cancer within U.S. women and understanding the psychological impacts of cancer diagnosis is an important public health issue. Brain-derived neutrophic factor (BDNF) is a gene involved in many neuronal processes that has been heavily studied in relation to psychiatric conditions. Most BDNF-focused DNA methylation studies have not considered the impacts of cell type heterogeneity, an important potential confounder. The purpose of this project was to analyze the relationship between BDNF DNA methylation and depression and anxiety symptoms in postmenopausal individuals recently diagnosed with breast cancer while considering the potential effects of cell type heterogeneity.
Methods: Genome-wide DNA methylation data were collected using the Illumina Infinium Methylation EPIC Beadchip from the peripheral blood samples of 48 postmenopausal individuals diagnosed with breast cancer. 44 CpG sites with strong evidence of being in BDNF regulatory regions were selected for examination. Depression symptoms were measured using the Beck Depression Inventory-II (BDI-II), and anxiety using the PROMIS Emotional Distress Anxiety Short Form. The relationship between BDNF DNA methylation and depression and anxiety symptoms in this sample was analyzed using linear regression while controlling for age and education history. Analyses were run twice, with and without correction for cell type heterogeneity.
Results: Of the 44 CpG sites analyzed, two had a suggestive association with depression (cg22043168 [β ̂ = 0.024, 95% Confidence Interval [CI] = (0.003-0.044), p = 0.023] and cg04481212 [β ̂ = 0.039, 95% CI = (0.008-0.070), p = 0.014] and one with anxiety (cg15313332 [β ̂ = -0.013, 95% CI= (-0.029-0.002), p = 0.093]. The results changed only marginally when correcting for cell type heterogeneity. No CpGs remained significant after correcting for multiple testing.
Conclusion: Suggestive associations were observed between anxiety/depression symptoms and three CpG sites. However, due to the small sample size and thus low statistical power, no substantive conclusions can be drawn regarding the relationship of BDNF DNA methylation and depression and anxiety symptoms. Despite this, this project contributes to public health by examining the potential role of BDNF DNA methylation as a biomarker of depression and anxiety symptoms in breast cancer patients.


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Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Kirkpatrick Heimke, Kaitlinkak387@pitt.edukak387
ContributionContributors NameEmailPitt UsernameORCID
Thesis advisorWeeks, Danielweeks@pitt.eduweeks0000-0001-9410-7228
Committee MemberHeinsberg, Laceylaw145@pitt.edulaw1450000-0002-7690-5485
Committee MemberConley, Yvetteyconley@pitt.eduyconleyUNSPECIFIED
Date: 17 May 2022
Date Type: Completion
Submission Date: 27 April 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 53
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Public Health Genetics
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: depression, anxiety, epigenetics, DNA methylation, BDNF, breast cancer
Date Deposited: 17 May 2022 16:12
Last Modified: 17 May 2024 05:15


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