Patients with Major Depressive Disorder Have Increased Triglyceride Levels

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A new meta-analysis showed how participants with major depressive disorder (MDD) had significantly elevated triglyceride levels.¹ This finding may explain the link between depression and cardiovascular and cerebrovascular events.

“Most of the included studies reported that the mean concentrations of [triglyceride] in patients with MDD and [healthy controls] were in the normal range (< 150 mg/dl),” wrote investigators, led by Di-Ru Xu, from the department of dermatology at University‑Town Hospital of Chongqing Medical University in China. “However, the [triglyceride] concentration in the MDD group was often near the upper normal limit.”

Individuals with depression are more likely to develop cardiovascular disease. A Johns Hopkins study published in 2023 found young adults who self-reported feeling depressed or having poor mental health days had greater rates of heart attacks, strokes, and heart disease risk factors compared with their peers without mental health issues.² Investigators suggested this could be because having depression could raise heart rate and blood pressure, as well as lead to unhealthy lifestyle choices such as smoking, drinking alcohol, sleeping less, and not being physically active.

Despite evidence of the link between depression and the increased risk of cardiovascular events, the underlying mechanism was not known.¹

Triglycerides, a major source of energy, are considered an independent risk factor for atherosclerosis, a condition that leads to myocardial infarction and ischemic stroke. An earlier study found lipid metabolites can differ between patients with major depressive disorder (MDD) and healthy subjects, leading investigators to suggest there is a significant alteration in triglyceride levels in patients with depression compared with healthy controls. Thus, investigators decided to conduct a new study to compare peripheral blood triglyceride levels between patients with MDD and healthy controls.

The team leveraged studies from PubMed, EMBASE, PsychINFO, and Cochrane Databases from inception up to March 2023 and reviewed articles listed in the references. They included 38 studies measuring the peripheral blood triglyceride levels in 2604 patients with MDD and 2372 controls.

Studies were included if they were case-control or cross-sectional that measured overnight fasting serum or triglyceride concentrations and had patients diagnosed with MDD based on the Statistical Manual of Mental Disorders (DSM), Chinese Classification and Diagnostic Disorder (CCMD), or International Classification of Disease (ICD). Healthy controls were included if they were not diagnosed with any disease. Participants were not included if they reported depressive symptoms due to other neuropsychiatric disorders, medical illnesses before MDD onset, special psychological conditions such as pregnancy or trauma, and medication that may affect triglyceride levels such as statins or niacin.

The meta-analysis revealed the mean peripheral blood triglyceride levels were significantly greater in patients with MDD than in controls (SMD, 0.31; 95% confidence interval [CI]: 0.16 to 0.46; P < 0.01). The team observed heterogeneity in this comparison (P < .01).

A subgroup analysis demonstrated significant differences in triglyceride levels among patients with MDD and healthy controls, but these differences were influenced by factors such as age, body mass index, and drug use (P < .05). However when comparing the overall triglyceride levels between the MDD group and the healthy control group, no significant differences were found.

Subgroup Analysis Findings

• Age:
  • < 45 years: SMD, 0.28; 95% CI, 0.10 to 0.47; P < .01
  • > 45 years: SMD, 0.39; 95% CI, 0.16 to 0.63; P < .01
• BMI:
  • BMI < 25: SMD, 0.27, 95% CI, 0.06 to 0.49, P < 0.01
  • BMI ≥ 25: SMD, 0.43, 95% CI, 0.19 to 0.67, P < 0.01
• Drug-Use:
  • Use: SMD, 0.42, 95% CI, 0.22 to 0.63, P < 0.01
  • Drug-naïve: SMD, 0.36, 95% CI, 0.20 to 0.53, P < 0.01

“These findings suggest the need to investigate the potential roles of [triglyceride] in the pathogenesis of depression, identify the potential utility of [triglyceride] and related lipids biomarkers in monitoring MDD and subsequent stroke or myocardial infarction, and measure potential benefits of low-[triglyceride] diet in MDD patients,” investigators concluded.

References

1. ^{Xu DR, Gao X, Zhao LB, et al. Association between triglyceride and depression: A systematic review and meta-analysis. PLoS One. 2024;19(10):e0311625. Published 2024 Oct 4. doi:10.1371/journal.pone.0311625}
2. ^{New Study Finds Depression, Poor Mental Health Linked to Higher Heart Disease Risks Among Young Adults. Johns Hopkins Medicine. January 30, 2023. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2023/01/new-study-finds-depression-poor-mental-health-linked-to-higher-heart-disease-risks-among-young-adults. Accessed October 18, 2024.}