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Molecular Mechanisms Underlying Depression : = A Multi-Omics Approach.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Molecular Mechanisms Underlying Depression :/
Reminder of title:	A Multi-Omics Approach.
Author:	Zhu, Yun.
Description:	1 online resource (166 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-02, Section: B.
Contained By:	Dissertations Abstracts International84-02B.
Subject:	Mental health. -
Online resource:	click for full text (PQDT)
ISBN:	9798837539435

Molecular Mechanisms Underlying Depression : = A Multi-Omics Approach.
Zhu, Yun.

Molecular Mechanisms Underlying Depression :A Multi-Omics Approach. - 1 online resource (166 pages)

Source: Dissertations Abstracts International, Volume: 84-02, Section: B.

Thesis (Ph.D.)--University of Florida, 2019.

Includes bibliographical references

Major depressive disorder (MDD) is a debilitating mental disorder that affects more than 350 million people worldwide. The prevalence of MDD varies according to gender, age, and racial/ethnic groups. Twin studies suggest that the heritability of MDD is estimated to be as high as 50%. As such, substantial effort has been made to identify genetic factors underlying MDD. However, all genetic variants identified so far explain only a small fraction of MDD variability, suggesting that environmental factors are also important contributors to depression pathogenesis. To date, the molecular mechanisms underlying MDD remain elusive. Leveraging the rich clinical and multi-omics data collected in two well-characterized community-based population cohorts, the Mood Methylation Study (MMS) and the Religious Orders Study and Memory and Aging Project (ROSMAP), I conducted integrated multi-omics data analyses to understand the molecular mechanisms of depression in younger and older adults. In a well-matched monozygotic (MZ) twin sample including 79 MZ twin pairs discordant on MDD (mean age 38.2 years), I conducted integrated DNA methylation and gene expression analysis to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with lifetime history of MDD in younger adults. The identified genes were enriched in pathways related to neuronal function and stress responses, and overrepresented in MDD GWAS loci. As the etiology of depression in younger and older age groups could be different, I conducted EWAS to identify differentially methylated genes associated with late life depressive symptoms. While several identified genes overlapped with differentially methylated genes in younger adults, most genes are specific to late life depressive symptoms. These findings support the hypothesis that molecular mechanisms underlying depression in younger individuals and older individuals could be different. Using gut microbiome data collected in 37 MZ twin pairs discordant on MDD, I found the microbiome metabolic pathways in plasma such as sphingolipid metabolism, D-glutamine, and D-glutamate metabolism, and histidine metabolism were significantly associated with lifetime history of MDD. In summary, this dissertation identified key genes and molecular pathways associated with MDD. These findings enhance our understanding of depression and are likely to provide novel biomarkers for depression and related disorders.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798837539435Subjects--Topical Terms:

564038
Mental health.
Subjects--Index Terms:

DepressionIndex Terms--Genre/Form:

554714
Electronic books.

Molecular Mechanisms Underlying Depression : = A Multi-Omics Approach.
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520 $a Major depressive disorder (MDD) is a debilitating mental disorder that affects more than 350 million people worldwide. The prevalence of MDD varies according to gender, age, and racial/ethnic groups. Twin studies suggest that the heritability of MDD is estimated to be as high as 50%. As such, substantial effort has been made to identify genetic factors underlying MDD. However, all genetic variants identified so far explain only a small fraction of MDD variability, suggesting that environmental factors are also important contributors to depression pathogenesis. To date, the molecular mechanisms underlying MDD remain elusive. Leveraging the rich clinical and multi-omics data collected in two well-characterized community-based population cohorts, the Mood Methylation Study (MMS) and the Religious Orders Study and Memory and Aging Project (ROSMAP), I conducted integrated multi-omics data analyses to understand the molecular mechanisms of depression in younger and older adults. In a well-matched monozygotic (MZ) twin sample including 79 MZ twin pairs discordant on MDD (mean age 38.2 years), I conducted integrated DNA methylation and gene expression analysis to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with lifetime history of MDD in younger adults. The identified genes were enriched in pathways related to neuronal function and stress responses, and overrepresented in MDD GWAS loci. As the etiology of depression in younger and older age groups could be different, I conducted EWAS to identify differentially methylated genes associated with late life depressive symptoms. While several identified genes overlapped with differentially methylated genes in younger adults, most genes are specific to late life depressive symptoms. These findings support the hypothesis that molecular mechanisms underlying depression in younger individuals and older individuals could be different. Using gut microbiome data collected in 37 MZ twin pairs discordant on MDD, I found the microbiome metabolic pathways in plasma such as sphingolipid metabolism, D-glutamine, and D-glutamate metabolism, and histidine metabolism were significantly associated with lifetime history of MDD. In summary, this dissertation identified key genes and molecular pathways associated with MDD. These findings enhance our understanding of depression and are likely to provide novel biomarkers for depression and related disorders.
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