Association between lipid levels and depression: a cross-sectional study
In this study, we investigated the relationship between depression and three lipid ratios, namely TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C. The results showed that there is an association between TG/HDL-C and depression in men. However, TC/HDL-C and LDL-C/HDL-C were not associated with depression in men and women.
Previous studies have mainly focused on the relationship between the aforementioned lipid ratios and cardiovascular disease and insulin resistance.13,14,15,16. However, no previous studies have been conducted to analyze the association between these ratios and depression. Some studies have demonstrated that the TC/HDL-C ratio is an important marker of cardiovascular risk and is mainly associated with insulin resistance13,14,16,17. As shown by the Framingham risk score, the risk of coronary heart disease increases with increasing TG/HDL-C ratio12. Additionally, a high TG/HDL-C ratio predicts the presence of small dense LDL particles and is useful in diagnosing the onset of insulin resistance and metabolic syndrome.18.
Previous studies have shown that low levels of TC and LDL-C are correlated with the onset of depression15,16,19,20. There are plausible explanations for this relationship. First, depression reduces a patient’s appetite, leading to low serum TC19. Second, cytokine activation, which interferes with cholesterol synthesis, occurs in depression21. Third, low cholesterol can reduce the availability of serotonin, making the patient more susceptible to depression.16.
A study of 8,390 people using data from the US National Health Survey demonstrated an association between depression and cholesterol levels. Depression was diagnosed using the PHQ-9 and LDL-C levels were divided into three groups: 15. Although LDL-C levels are known to be associated with depression, our study identified a relationship between cholesterol levels and depression, revealing the importance of assessing lipid levels.
Low cholesterol is associated with indicators of mental health. The association between low cholesterol and depression has been consistently proven in laboratory studies. Additionally, less supportive or depressive behaviors have been observed in studies of low cholesterol animals.22.23. In a previous report, patients who used long-term cholesterol-lowering drugs showed signs of depression20. These results may be explained by the significant correlation between plasma serotonin and low cholesterol concentration, which has been previously reported.2.24.
Similar to the present study, some previous studies have shown that depression is associated with high levels of TG and low levels of HDL-C25.26. A recent meta-analysis performed to determine whether lipid parameters differed between healthy individuals and patients with first episode major depressive disorder found that increased TG levels and decreased HDL- C are associated with the first episode of major depressive disorder25. Although TG and HDL-C levels are known to be associated with depression, our study identified a relationship between the TG/HDL-C ratio and depression, revealing that lipid ratio assessment is crucial.
The serum lipid levels of people with depression and suicidal ideation were analyzed in a previous study using data from KNHANES, the results of which showed a significant association of elevated HDL-C and TG levels with depression.26. However, unlike the present study, it was conducted using KNHANES data from 2014 and depression was diagnosed as a PHQ-9 score ≥ 5.
Potential mediators of depression in lipids or lipoproteins and their association with symptom heterogeneity were investigated in a previous study27. The results indicated that melancholic features are independently associated with low HDL-C, whereas atypical depression is independently associated with high TC and LDL-C.27.
The results of the present study are consistent with findings from previous studies that suggest depression is associated with metabolic syndrome. Research on the relationship between metabolic syndrome and depression has been actively carried out in recent years.6,28,29. Several possible mechanisms may be behind this correlation between metabolic syndrome and depression. People with depression are more likely to engage in unhealthy behaviors, such as smoking, drinking alcohol, unhealthy diet and lifestyle, and not adhering to medical treatment, than those who are not. .29. In addition, depression causes dysregulation of the hypothalamic-pituitary-adrenal axis, which may explain its association with metabolic syndrome.30. There is a study that analyzed whether CRP and TG were related to suicide attempts in patients with major depressive disorder. The results of the study showed that CRP was significantly higher in suicidal subjects than in depressed patients who did not attempt suicide and in healthy controls. TG levels were significantly higher in depressed patients than in healthy controls31.
The presence of depression was analyzed in this study using PHQ-9 scores. The usefulness of the PHQ-9 score as a diagnostic criterion for depression has already been verified in Korea and other countries.7,8,9. However, the score used as a diagnostic criterion varies from one study to another. In the present study, a PHQ-9 score≧10 was diagnosed as depression. In the study by Kroenke et al.19, a 9-point threshold had a high sensitivity of 95% and specificity of 84%. However, 10 points, which are simple and easy to remember or apply in real clinical settings, have been suggested as the optimal threshold.32.
A review of reviews reports that the association between depression and lipid profile leads to several conclusions33. That is, some studies reported that the lower the cholesterol level, the more depression was affected, and other studies reported no relationship. Although our results cannot hypothesize an association between lipid profile and depression, it can be hypothesized that at least TG/HDL-C is associated with depression mediated by weight gain or a mediocre lifestyle.
The present study is significant because it is the first to analyze the association between lipid levels and depression in a large population. The results of this study indicate that TC/HDL-C and LDL-C/HDL-C are not associated with depression. However, this result may have been influenced by the sample size, design, and participants of this study. Therefore, future large scale prospective clinical studies are needed to verify this conclusion.
This study has certain limitations. First, we used data from a study in which depression and lipid levels were measured only once. Depression and cholesterol levels are likely to fluctuate over time; thus, ignoring these fluctuations may have obscured the observed association. Second, the data used in the study came from large-scale government surveys, and there were several limitations to the statistical analysis. The degree and characteristics of depression, the presence of suicidal ideation/attempts have not been studied. In addition, the administration of psychotropic drugs or cognitive therapy has not been studied. Third, because this was a cross-sectional study, it was difficult to establish the relationship between low cholesterol and depression.