Analyzing the genes and pathways related to major depressive disorder via a systems biology approach

Fan, Ting; Ying, Haoqiang; Xin, Juncai; Zhao, Mengwen; Wang, Ju

doi:10.1002/brb3.1502

Cited by 36 publications

(20 citation statements)

References 77 publications

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“…The identified KEGG pathways (i.e., “retrograde endocannabinoid signaling” and “neuroactive ligand-receptor interaction”) have been reported to modulate a wide variety of synaptic neurotransmissions or neural functions, including cognition, motor control, and pain 64 , 65 . Abnormalities or dysregulations of these pathways have been implicated in MDD 66 .…”

Section: Discussionmentioning

confidence: 99%

Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

et al. 2021

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Major depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.

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Section: Discussionmentioning

confidence: 99%

Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

et al. 2021

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“…The thyroid hormone signaling pathway is activated by the consumption of glucose-rich foods [ 33 ], mainly through Ca 2+ currents that are modulated by channels such as CACNA1C or CACNA1D (genes found in the BD-PRS) [ 34 , 35 , 36 ]. It is known that individuals with BD and psychosis have an increased risk of diabetes mellitus (i.e., high blood glucose levels) [ 37 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative Genomic–Epigenomic Analysis of Clozapine-Treated Patients with Refractory Psychosis

et al. 2021

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Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients with refractory psychosis, but it has also been proposed as an effective mood stabilizer; however, the complex mechanisms of action of CLZ are not yet fully known. To find predictors of CLZ-associated phenotypes (i.e., the metabolic ratio, dosage, and response), we explore the genomic and epigenomic characteristics of 44 patients with refractory psychosis who receive CLZ treatment based on the integration of polygenic risk score (PRS) analyses in simultaneous methylome profiles. Surprisingly, the PRS for bipolar disorder (BD-PRS) was associated with the CLZ metabolic ratio (pseudo-R2 = 0.2080, adjusted p-value = 0.0189). To better explain our findings in a biological context, we assess the protein–protein interactions between gene products with high impact variants in the top enriched pathways and those exhibiting differentially methylated sites. The GABAergic synapse pathway was found to be enriched in BD-PRS and was associated with the CLZ metabolic ratio. Such interplay supports the use of CLZ as a mood stabilizer and not just as an antipsychotic. Future studies with larger sample sizes should be pursued to confirm the findings of this study.

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“…Several affected hypothalamic regulatory pathways in 5X-MTHF compared to 5X-FA dams have been previously shown to be associated with obesity, mood disorders and addictive behavior, including food addiction [ 64 , 65 ]. These pathways include, but are not limited to, the KEGG neuroactive ligand-receptor interaction, GABAergic synapse, and retrograde endocannabinoid synapse.…”

Section: Discussionmentioning

confidence: 99%

[6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth

et al. 2020

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[6S]-5-methyltetrahydrofolic acid (MTHF) is a proposed replacement for folic acid (FA) in diets and prenatal supplements. This study compared the effects of these two forms on maternal metabolism and hypothalamic gene expression. Pregnant Wistar rats received an AIN-93G diet with recommended FA (1X, 2 mg/kg, control), 5X-FA or equimolar levels of MTHF. During lactation they received the control diet and then a high fat diet for 19-weeks post-weaning. Body weight, adiposity, food intake, energy expenditure, plasma hormones, folate, and 1-carbon metabolites were measured. RNA-sequencing of the hypothalamus was conducted at parturition. Weight-loss from weaning to 1-week post-weaning was less in dams fed either form of the 5X vs. 1X folate diets, but final weight-gain was higher in 5X-MTHF vs. 5X-FA dams. Both doses of the MTHF diets led to 8% higher food intake and associated with lower plasma leptin at parturition, but higher leptin at 19-weeks and insulin resistance at 1-week post-weaning. RNA-sequencing revealed 279 differentially expressed genes in the hypothalamus in 5X-MTHF vs. 5X-FA dams. These findings indicate that MTHF and FA differ in their programing effects on maternal phenotype, and a potential adverse role of either form when given at the higher doses.

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Analyzing the genes and pathways related to major depressive disorder via a systems biology approach

Cited by 36 publications

References 77 publications

Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

Integrative Genomic–Epigenomic Analysis of Clozapine-Treated Patients with Refractory Psychosis

[6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth

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