A Systematic Analysis on the Genes and Their Interaction Underlying the Comorbidity of Alzheimer's Disease and Major Depressive Disorder

Guo, Pengyi; Chen, Shasha; Wang, Hao; Wang, Yaogang; Ju, Wang

doi:10.3389/fnagi.2021.789698

Cited by 9 publications

(6 citation statements)

References 83 publications

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“…The pathogenesis of Alzheimer’s disease (AD) is believed to be closely related to depression [ 106 , 107 ]. In particular, major depression and AD share biological processes and pathways, including 77 disease-related genes and 102 pathways [ 108 ]. Amyloid β (Aβ) is one of the vital shared pathogenic targets [ 109 , 110 , 111 , 112 ].…”

Section: Depression-associated Seh Promotes Liver Dysfunction and Bre...mentioning

confidence: 99%

Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism

Ganesan²,

Wu³

et al. 2022

Molecules

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Breast cancer (BC) is a serious global challenge, and depression is one of the risk factors and comorbidities of BC. Recently, the research on the comorbidity of BC and depression has focused on the dysfunction of the hypothalamic–pituitary–adrenal axis and the persistent stimulation of the inflammatory response. However, the further mechanisms for comorbidity remain unclear. Epoxide metabolism has been shown to have a regulatory function in the comorbid mechanism with scattered reports. Hence, this article reviews the role of epoxide metabolism in depression and BC. The comprehensive review discloses the imbalance in epoxide metabolism and its downstream effect shared by BC and depression, including overexpression of inflammation, upregulation of toxic diols, and disturbed lipid metabolism. These downstream effects are mainly involved in the construction of the breast malignancy microenvironment through liver regulation. This finding provides new clues on the mechanism of BC and depression comorbidity, suggesting in particular a potential relationship between the liver and BC, and provides potential evidence of comorbidity for subsequent studies on the pathological mechanism.

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Section: Depression-associated Seh Promotes Liver Dysfunction and Bre...mentioning

confidence: 99%

Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism

Ganesan²,

Wu³

et al. 2022

Molecules

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“…Recent reports have revealed that there is a strong relationship between MDD and AD [18,19]. For example, a systematic analysis result revealed shared pathways and biological processes between MDD and AD and offered a hint for the comorbidity of MDD and AD [20]. Depression could act as a risk factor for the late development of AD [21].…”

Section: Introductionmentioning

confidence: 99%

Identification of novel biomarkers linking depressive disorder and Alzheimer’s disease based on an integrative bioinformatics analysis

Jiang¹,

Ma²,

Zhang

et al. 2023

BMC Genom Data

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Background Previous reports revealed that a history of major depressive disorder (MDD) increased the risk of Alzheimer’s disease (AD). The immune disorder is associated with MDD and AD pathophysiology. We aimed to identify differentially expressed immune-related genes (DEIRGs) that are involved in the pathogenesis of MDD and AD. Methods We downloaded mRNA expression profiles (GSE76826 and GSE5281) from the Gene Expression Omnibus (GEO) database. The R software was used to identify DEIRGs for the two diseases separately. Functional enrichment analysis and PPI network of DEIRGs were performed. Finally, the relationship between shared DEIRGs and immune infiltrates of AD and MDD were analyzed, respectively. Results A total of 121 DEIRGs linking AD and MDD were identified. These genes were significantly enriched in immune-related pathways, such as the JAK-STAT signaling pathway, regulation of chemotaxis, chemotaxis, cytokine-cytokine receptor interaction, and primary immunodeficiency. Furthermore, three shared DEIRGs (IL1R1, CHGB, and NRG1) were identified. Correlation analysis between DEIRGs and immune cells revealed that IL1R1 and NRG1 had a negative or positive correlation with some immune cells both in AD and MDD. Conclusion Both DEIRGs and immune cell infiltrations play a vital role in the pathogenesis of AD and MDD. Our findings indicated that there are common genes and biological processes between MDD and AD, which provides a theoretical basis for the study of the comorbidity of MDD and AD.

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“…This lack of understanding arises partly from the structural and dynamic complexity of the systems involved and partly from the traditional approach of Western medicine, which tends to view health through the lens of isolated structural and functional elements rather than fully integrated dynamic systems. 8,9,10,11,12 To analyze effects of perturbations in these complex systems, we and others have developed network-and Information Theory-based methods to characterize underlying cause-effect relationships. 13,14,15,16,17,18 These approaches provide valuable insights into comorbidities and their impact on health.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Deficiency-Associated Comorbidities: A Protein Network Dynamics Perspective

Fliri¹,

Kajiji²

2023

MRAJ

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Vitamin D deficiency has been linked to numerous comorbid diseases. Despite this recognition, the effectiveness of vitamin D supplementation in improving clinical outcomes remains uncertain. To shed light on the underlying cause-effect relationships and molecular mechanisms involved, we analyzed effects of over 4000 diseases on information transfers between biological processes in human tissues. Spectral clustering of the data generated identified relationships between disease phenotypes and perturbations of protein network-network interactions mediating information transfers in tissues. Examination of these relationships discovered an integrated regulatory scheme involving interactions between 188 proteins responsive to vitamin D (vitamin D interactome). Functional analysis established a central role of fifteen proteins (core vitamin D interactome) in vitamin D pharmacology and their involvement in multiple reciprocal feedback loops. Identification of functions affected by this core regulatory framework provides new insights into relationships between vitamin D deficiency-associated comorbidities, epigenetic regulation of vitamin D pharmacology, and impact of mutations on disease. Recognition of these functional relationships suggests that vitamin D associated comorbidities may not be fully treatable by vitamin D supplementation alone. Further examination of consequences of perturbations of protein interactions within the core vitamin D interactome identified 590 morbidities exhibiting physical changes co-expressed in vitamin D deficiency. Further analysis revealed that these comorbidities can be differentiated based on cause-effect relationships defined by characteristic patterns of physical abnormalities and effects on protein network interactions. These findings demonstrate the utility of systems biology-based cause-effect analyses to unravel complex relationships involving multiple diseases and multiple biological processes; thereby providing a more comprehensive understanding of comorbidities and the impact of vitamin D deficiency on health. Article Details How to Cite

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A Systematic Analysis on the Genes and Their Interaction Underlying the Comorbidity of Alzheimer's Disease and Major Depressive Disorder

Cited by 9 publications

References 83 publications

Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism

Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism

Identification of novel biomarkers linking depressive disorder and Alzheimer’s disease based on an integrative bioinformatics analysis

Vitamin D Deficiency-Associated Comorbidities: A Protein Network Dynamics Perspective

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