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. 2024 Apr 17:11:1322254.
doi: 10.3389/fnut.2024.1322254. eCollection 2024.

Association between cheese and fish consumption and the occurrence of depression based on European population: mediating role of metabolites

Yan Chen  1 , Jixin Lin  1 , Ming Tao  2
Affiliations

Association between cheese and fish consumption and the occurrence of depression based on European population: mediating role of metabolites

Yan Chen et al. Front Nutr. .

Abstract

Background: The consumption of cheese and fish has been linked to the onset of depression. However, the connection between consuming cheese, consuming fish, experiencing depression, and the pathways that mediate this relationship remains unclear. The purpose of this research was to investigate the potential association between the consumption of cheese and fish and the occurrence of depression. Moreover, it is important to identify any metabolites that might be involved and understand their respective roles and functions.

Methods: A two-step, two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) data on cheese, non-oily fish, and oily fish consumption and depression, along with 12 alternate mediators. The study included a total of 451,486 participants in the cheese consumption group, 460,880 in the non-oily fish consumption group, 460,443 in the oily fish consumption group, and 322,580 with a diagnosis of depression. The single nucleotide polymorphism (SNP) estimates were pooled using inverse-variance weighted, weighted median, MR-Egger, simple mode, and weighted mode.

Results: The data we collected suggested that consuming more cheese correlated with a lower likelihood of experiencing depression (OR: 0.95; 95% CI: 0.92 to 0.98). Neither non-oily fish nor oily fish consumption was directly linked to depression onset (p = 0.08, p = 0.78, respectively). Although there was a direct causal relationship with depression, the mediating relationship of triglycerides (TG), total cholesterol in large HDL, cholesterol to total lipids ratio in large HDL, free cholesterol to total lipids ratio in large HDL, glycine, and phospholipids to total lipids ratio in very large HDL of cheese intake on depression risk were - 0.002 (95% CI: -0.023 - 0.020), -0.002 (95% CI: -0.049 - 0.045), -0.001 (95% CI: -0.033 - 0.031), -0.001 (95% CI: -0.018 - 0.015), 0.001 (95% CI: -0.035 - 0.037), and - 0.001 (95% CI: -0.024 - 0.021), respectively. The mediating relationship of uridine, free cholesterol to total lipids ratio in large HDL, total cholesterol in large HDL, acetoacetate, and 3-hydroxybutyrate (3-HB) between non-oily fish consumption and depression risk were 0.016 (95% CI: -0.008 - 0.040), 0.011 (95% CI: -1.269 - 1.290), 0.010 (95% CI: -1.316 - 1.335), 0.011 (95% CI: -0.089 - 0.110), and 0.008 (95% CI: -0.051 - 0.068), respectively. The mediation effect of uridine and free cholesterol to total lipids ratio in large HDL between intake of oily fish and the risk of depression was found to be 0.006 (95% CI: -0.015 - 0.028) and - 0.002 (95% CI: -0.020 - 0.017), respectively. The correlation between eating cheese and experiencing depression persisted even when adjusting for other variables like Indian snacks, mango consumption, sushi consumption, and unsalted peanuts using multivariable MR.

Conclusion: The consumption of cheese and fish influenced the likelihood of experiencing depression, and this may be mediated by certain metabolites in the body. Our study provided a new perspective on the clinical treatment of depression.

Keywords: Mendelian randomization; cheese; depression; fish; mediation; metabolites.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of the MR study design. HDL, high-density lipoprotein; MR, Mendelian randomization.
Figure 2
Figure 2
Evidence for selection of mediators that play a role in the association between consumption of cheese and fish and depression. (A) Causal associations between candidate mediators and depression in the cheese consumption group; (B) Causal associations between cheese consumption and candidate mediators, which were confirmed to influence depression; (C) Causal associations between candidate mediators and depression in the non-oily fish consumption group; (D) Causal associations between non-oily fish consumption and candidate mediators, which were confirmed to influence depression; (E) Causal associations between candidate mediators and depression in the oily fish consumption group; (F) Causal associations between oily fish consumption and candidate mediators, which were confirmed to influence depression. “Selection” indicates whether the candidate mediators were selected for subsequent analyses. The IVW method was used for the main analysis. Sensitivity analyses included the MR-Egger and WM shown in the figure as well as the simple mode and weighted mode methods shown in Supplementary Tables S6, S8. FDR, false discovery rate; IVW, inverse-variance weighted.
Figure 3
Figure 3
(A) Forest plots of leave-one-out analyses for causal SNP relationship between cheese consumption and depression. The error bars indicate the 95% confidence interval (CI). (C) Scatter plots for causal SNP relationship between cheese consumption and depression. Each black point represents each SNP on the exposure (horizontal axis) and the outcome (vertical axis) plotted with error bars corresponding to the standard error (SE). The slope of each line corresponds to the combined estimate using each method of the inverse-variance weighted (light blue line), MR-Egger (blue line), simple mode (light green line), weighted median (green line), and weighted mode (pink line). SNP: single nucleotide polymorphism, MR, Mendelian randomization. (B) Forest plot to visualize causal effect of each single SNP on depression. (D) Funnel plots to visualize overall heterogeneity of MR estimates for the effect of cheese consumption on depression. IVW indicates inverse-variance weighted; and MR, Mendelian randomization.
Figure 4
Figure 4
(A) Relationship between cheese consumption and depression assessed by the primary MR analyses from the GWAS dataset; (B) MR estimates for the causal relationships between cheese consumption and mediators (left) and the causal relationships between mediators and depression (right); (C) MR estimates for the causal relationships between non-oily fish consumption and mediators (left) and the causal relationships between mediators and depression (right); (D) MR estimates for the causal relationships between oily fish consumption and mediators (left) and the causal relationships between mediators and depression (right).
Figure 5
Figure 5
(A) Two-step MR analysis framework; (B) DAG for the proposed causal interactions for metabolites in the pathway between cheese and fish consumption and depression. The black arrows represent causal pathways from cheese and fish consumption through mediators identified in this MR study to depression. The gray arrows represent other plausible pathways linking cheese and fish consumption to depression that we did not investigate in this study. DAG, directed acyclic diagram; MR, Mendelian randomization.
Figure 6
Figure 6
(A) Enrichment analysis of pathways related to cheese consumption and the treatment of depression. (B) Enrichment analysis of pathways related to non-oily fish consumption and the treatment of depression. (C) Enrichment analysis of pathways related to oily fish consumption and the treatment of depression. (D) Eight key metabolic pathways related to non-oily fish consumption and the treatment of depression.
Figure 7
Figure 7
Molecular docking. Binding mode of glycine with glutamate receptor 2.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study has been supported by the National Key Research and Development Program of China under grant no. 2022YFE0199300.