In our cross-sectional study of 29,561 adult participants, we found that the likelihood of participants developing depression increased as the NHHR index rose. A linear relationship between NHHR index and depression was demonstrated using smooth curve fitting. In the subgroup analyses and interaction tests conducted, we hypothesized that two stratification factors, BMI <25 kg/m2 and absence of sleep disorders, may influence the relationship between NHHR and the prevalence of depression.
This is the only study that we are aware of that evaluates the relationship between NHHR and higher rates of depression. Previous studies have discussed associations between depression and other biomarkers.The association between relative adiposity, an indicator of obesity, and depression was found to be most significant in the US adult population in a cross-sectional study conducted by Xianlin Zhu et al. (24). Depression has also been reported to be associated with lymphocyte to HDL ratios, leading to the suggestion that immune dysfunction or inflammatory factors may be a key contributor to depression(25).NHHR, as an emerging biomarker, has received much attention for its regulation of diseases such as atherosclerosis, diabetes, kidney stones, and periodontitis. Despite the lack of previous studies describing the relationship between NHHR and psychiatric disorders, there have been many reports of NHHR-related markers, including non-HDL, TC, HDL, apolipoproteins, and low-density lipoproteins.Non-HDL cholesterol is the sum of all kinds of lipoprotein cholesterol in the blood except HDL cholesterol, and relevant research investigations have found that apolipoprotein (b) and HDL, the main components of non-HDL cholesterol, are the main lipid metabolism indexes constituting atherosclerosis, and that atherosclerosis is prone to cause endothelial function damage at the beginning, and increase in vascular oxidative stress, which further causes nitric oxide-dependent diminished vasodilatory function, which in turn causes major depressive disorder (26-29).Numerous investigations have revealed that lower levels of total cholesterol, LDL and non-HDL increase the risk of depression (30-33).It has been suggested that low plasma cholesterol levels can reduce the synthesis of neuromodulators such as steroids, which can lead to depressed mood (34,35).In a cross-sectional study of the relationship between lipids and depressive episodes in postmenopausal women, it was found that after quintiles of HDL-C and LDL-C were used as continuous variables, it was concluded that lower concentrations of HDL-C and LDL-C were associated with the risk of developing depression (36).Xianlin Zhu et al. analyzed the positive association between non-HDL-C and depression in 42,143 subjects in a cross-sectional study, and the relationship was more significant in men (37).In view of the above relationship between each of the lipid indicators of depression, we believe that it is necessary for the study of the association between NHHR and depression. Specifically, the results of our subgroup analyses showed that age, gender, race, smoking, alcohol consumption, PIR, coronary heart disease, hypertension, diabetes mellitus, and stroke had no dependence on the positive correlation between NHHR and depression (P for interaction > 0.05), and the baseline characterization of participants as well as the smoothed curve fitting showed that, compared with the no depression group, subjects with depression subjects had a more significant association with NHHR and that for each unit increase in NHHR, subjects were 23% more likely to have depression.
Our study has a number of strengths; firstly, our data came from having a large, accurate and reliable NHANES database, and secondly, we adjusted for multiple confounding variables and performed smoothed curve fitting and subgroup analyses to validate the stability of our results and to more accurately analyze the effects of different single factors on the association between NHHR and depression. However, this paper also has limitations. First, because this paper is a cross-sectional study design,It is unable to elucidate the causal connection between NHHR and depression, and longitudinal studies with larger sample sizes are needed in the future. Second, even though we took some probable covariates into account, we are unable to totally rule out the impact of additional potential confounders. Finally, in the future, we need to further analyze the mechanism behind this correlation through experiments.