Among the male participants, Among the female participants, 6, Factors that affect the probability of depression and the relationship between the lipid ratio and depression were analyzed after adjusting for variables.

Among men, the probability of depression was Among women, the probability of depression was Previous studies have mainly focused on the relationship between the abovementioned lipid ratios and cardiovascular disease and insulin resistance 13 , 14 , 15 , However, no previous study has been conducted to analyze the association between these ratios and depression.

Previous studies have shown that low TC and LDL-C levels are correlated with the onset of depression 15 , 16 , 19 , There are some plausible explanations for this relationship. Second, cytokine activation, which interferes with cholesterol synthesis, occurs in depression Third, low cholesterol level can reduce the availability of serotonin, making the patient more susceptible to depression A study conducted on people using data from the National Health Survey of the United States demonstrated an association between depression and cholesterol level.

However, LDL-C and HDL-C were not associated with moderate depression Although the LDL-C level is known to be associated with depression, our study identified a relationship between cholesterol ratio and depression, revealing the importance of evaluating lipid ratio.

Low cholesterol levels are associated with mental health indicators. The association between low cholesterol level and depression has been consistently proven in laboratory studies. In addition, less favorable or depressive behaviors were observed in studies of animals with low cholesterol levels 22 , In a previous report, patients who used cholesterol-lowering drugs long-term showed signs of depression These findings can be explained by the significant correlation between plasma serotonin and low cholesterol concentration, which has been previously reported 2 , Similar to the present study, some previous studies showed that depression is associated with high TG and low HDL-C levels 25 , A recent meta-analysis performed to investigate whether lipid parameters differed between healthy individuals and patients with first-episode major depressive disorder revealed that elevated TG and decreased HDL-C levels are associated with first-episode major depressive disorder The serum lipid levels of people with depression and suicidal ideation have been analyzed in a previous study using KNHANES data, the results of which showed a significant association of high HDL-C and TG levels with depression The potential mediators of depression in lipids or lipoproteins and their association with the heterogeneity of symptoms have been investigated in a previous study The results indicated that melancholic features are independently associated with low HDL-C level, whereas atypical depression is independently associated with high TC and LDL-C levels The results of the present study are consistent with the findings of previous studies that suggest that depression is associated with metabolic syndrome.

Research on the relationship between metabolic syndrome and depression has been actively conducted in recent years 6 , 28 , Several possible mechanisms may be behind this correlation between metabolic syndrome and depression.

Individuals with depression are more likely to engage in unhealthy behaviors, such as smoking, drinking alcohol, unhealthy diet and lifestyle, and non-compliance with medical treatment, than those who are not In addition, depression causes dysregulation of the hypothalamic—pituitary—adrenal axis, which may explain its association with metabolic syndrome 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 suicide attempters than in depressed patients who did not attempt suicide and in healthy controls.

TG levels were significantly higher in depressed patients compared to healthy controls 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 in other countries 7 , 8 , 9.

However, the score used as a diagnostic criterion varies from study to study. In the study by Kroenke et al. However, 10 points, which is simple and easy to remember or apply in actual clinical settings, has been suggested as the optimal cutoff point A review journal reports that the association between depression and lipid profile leads to several conclusions That is, some studies reported that the lower the cholesterol level, the more adversely affected depression, and other studies reported no relationship.

The present study is meaningful because it is the first to analyze the association between lipid ratios and depression in a large population.

However, this finding 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 some 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, failure to account for these fluctuations may have clouded the observed association.

Second, the data used in the study are from large-scale government surveys, and there were several limitations in statistical analysis. Additionally, administration of psychotropic medications or cognitive therapy were not investigated.

Third, as this was a cross-sectional study, it was difficult to ascertain the relationship between low cholesterol level and depression. Depression is not just a psychiatric disease, but a disease that needs to be approached in terms of metabolic abnormalities as well.

In this study, we measured the lipid ratio in patients with depression and brought attention to mental health in individuals with abnormal lipid ratio. Future studies reflecting the limitations of our study may provide a clinical basis for lipid metabolism in depression.

Publicly available datasets were analyzed in this study, which could be used after obtaining approval from the relevant authorities.

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Tedders, S. Low cholesterol is associated with depression among US household population. Manfredini, R. Already, researchers have identified several biologic risk factors for depression, including a family history of the disease and certain neurologic changes in the elderly. And now, Suarez said there is evidence to suggest that having low cholesterol alters the way brain cells function.

He said it is believed that brain cells with low levels of cholesterol have fewer serotonin receptors, preventing them from properly using this mood-stabilizing brain chemical.

Further, cholesterol's importance throughout the body is gaining more prominence as researchers link it to a variety of critical functions, such as how immune cells work, said Suarez.

Long involved in studying the effects of stress and depression in women, Suarez' interest in cholesterol and mood grew out of a series of large studies conducted years ago in men with high cholesterol.

While men in the study were reducing their cholesterol levels through medications, their overall mortality rate was not declining. In fact, the rate of suicide and death from violent causes increased during the study, leading researchers to theorize that low cholesterol levels were causing mood disturbances.

Based on these findings, Suarez conducted several small pilot studies in women, adding a measurement of anxiety to the research, before conducting the current study in women aged Several studies have found a correlation between low cholesterol and depression, but the results are inconsistent. Data from the National Health and Nutrition Examination Survey NHANES were utilized in this cross-sectional study.

The analysis of the relationship between cholesterol and depression was performed at three levels: low total cholesterol, low high-density lipoprotein HDL cholesterol and low-density lipoprotein LDL cholesterol.

Age, sex, educational level, race, marital status, self-rated health, alcohol status, smoking status, body mass index BMI , poverty income ratio, physical function, comorbidities, and prescription use were considered potential confounders. The missing data were handled by multiple imputations of chained equations.

Logistic regression was used to assess the relationship between low cholesterol and depression. The results stratified by sex also showed no association between low total cholesterol, low LDL cholesterol, low HDL cholesterol and depression in either men or women.

This population-based study did not support the assumption that low cholesterol was related to a higher risk of depression.

This information may contribute to the debate on how to manage people with low cholesterol in clinical practice. Depression is a common but serious illness defined by persistent sadness and a loss of interest in things that one generally enjoys doing for at least two weeks [ 1 ].

The World Health Organization WHO reported that approximately 4. In terms of lost health, the consequences of depression are substantial. The WHO estimates that depression is a leading cause of disease burden and disability, with data showing that depression accounts for 7.

Normal cholesterol concentration is essential for receptor function, synaptic plasticity, and myelin formation in the central nervous system [ 3 , 4 , 5 , 6 , 7 ]. Given that the association is well demonstrated between neuronal deficits and depression [ 8 , 9 ], a hypothesis has emerged that the link between depression and low cholesterol may have a neurobiological mechanism [ 3 ].

Several studies have reported that lowering cholesterol led to an increase in death rates due to other reasons, such as murder, accidents, and suicide, which offset the benefits of reducing heart disease [ 10 , 11 , 12 , 13 , 14 ].

Because depression is an important risk factor for suicide and fatal accidents, an idea has emerged that there is a link between depression and low cholesterol, based on both biological and clinical evidence [ 15 ]. Several studies have further investigated the connection between low cholesterol levels and depression, but the conclusions are contradictory.

On the one hand, several studies [ 15 , 16 , 17 , 18 ] described that low cholesterol was correlated with a higher risk of depression.

However, some studies reported that no significant association was discovered between depression and low cholesterol [ 19 , 20 ]. The small sample sizes, sampling bias, and limited controls for confounding might be the most important reasons for the different conclusions.

The lack of consensus regarding a conclusion of the inconsistencies and the important clinical meaning created a need for further exploration of the association. This study aimed to identify the relationship between low cholesterol and depression based on the National Health and Nutrition Examination Survey NHANES dataset, with a large sample size representing the population of the United States and controls for confounding factors.

In addition, associations were examined separately by sex to explore the sex differences in these relationships. The data from the NHANES were utilized in this cross-sectional study. The NHANES is a publicly available database, with a representative sample of the United States population [ 21 ].

To produce reliable statistics, the NHANES selected participants by a stratified multistage probability design, and certain racial, age, and income groups were oversampled.

Participants in the NHANES — were included in this study. The analysis was performed at three levels: low total cholesterol, low-density lipoprotein LDL cholesterol, and high-density lipoprotein HDL cholesterol.

Because total cholesterol, LDL cholesterol, and HDL cholesterol were not examined in the same group of people, the analysis was based on three different samples. Sample 1 was selected for the analysis of total cholesterol, Sample 2 for HDL cholesterol, and Sample 3 for LDL cholesterol.

Depression was evaluated by the PHQ—9, a 9-item validated questionnaire evaluating depressive symptoms within the last 2 weeks [ 22 ]. The PHQ-9 classifies depressive symptoms into four levels nearly every day; more than half the days; several days; and not at all.

A score of 10 or higher was used to identify subjects with major depressive disorder MDD. The questionnaire was completed at a mobile exam center, and trained interviewers asked the questions using a computer-assisted personal interview system.

Blood specimens were analyzed at the University of Minnesota. Cholesterol levels were measured by an enzymatic assay: cholesterol esterase converted esterified cholesterol to cholesterol, which then produced hydrogen peroxide and cholestenone.

After reacting with 4-aminophenazone by peroxidase, hydrogen peroxide then produced a colored product. This method is specific for cholesterol because it is a single reagent endpoint reaction. In this study, the total cholesterol levels were classified into a normal group 4.

LDL cholesterol levels were classified as normal 1. Several potential confounding variables were taken into account. Race was classified as Mexican American, Non-Hispanic White, Non-Hispanic Black, other Hispanic, and other race. Marital status was classified as living with partner or married, widowed or divorced, never married, and separated.

Educational level was divided into less than 9th grade, th grade, high school graduate, some college or AA degree, college graduate or above.

Smoking status and alcohol status were classified as current, former, and never. Body mass index BMI was divided into overweight i. Self-rated health was divided into excellent, very good, good, fair, or poor. The poverty income ratio PIR was used to measure income, which was classified as poor i.

Physical function was measured by six questions from the questionnaire that were consistent with previous literature [ 26 ], including 1 walking a quarter-mile; 2 lifting or carrying heavy objects; 3 standing from an armless chair; 4 climbing 10 steps; 5 stooping, crouching, or kneeling; and 6 standing for long periods [ 26 ].

If a person had any trouble performing these activities, they were considered to have an existing physical functioning limitation. The number of difficult problems was summarized on a scale of Stata The variance estimation and weights were used to adjust for the complex survey method by Stata's svy.

This study investigated the relationship between depression and low total cholesterol, low HDL cholesterol, and low LDL cholesterol in three different samples, and all statistical analyses were performed for each sample. Categorical data are described as percentages. Then, three logistic regression models were calculated.

Model 1 only included cholesterol, and no covariates were adjusted; Model 2 included cholesterol, age, and sex; Model 3 included all the covariates that were significant in the univariate analysis.

Figure 1 summarizes the results of logistic regression, and there was no association between low total cholesterol, low LDL cholesterol, low HDL cholesterol, and depression after adjustment for potential confounding factors in Model 3 for Sample 1, Sample 2, and Sample 3.

The results were the same after stratification by sex in all three Samples. Association between low total cholesterol, low HDL-cholesterol, low LDL-cholesterol and depression.

For the analysis of total cholesterol in Sample 1, a total of subjects were included. Of these, there were people with depression weighted proportion 7.

Table 1 presents the characteristics of the weighted population. In the weighted sample, there was a significant difference in sex, race, educational level, family income, marital status, smoking status, alcohol status, BMI, physical function, coronary heart disease, cancer, stroke, high blood pressure, and diabetes excluding prescription use.

Therefore, these factors were added to the multivariate logistic regression model. For the analysis of HDL cholesterol in Sample 2, a total of subjects were included. In the weighted sample, there was a significant difference in sex, race, educational level, family income, marital status, smoking status, alcohol status, BMI, physical function, diabetes, stroke, coronary heart disease, and high blood pressure detailed information can be found in Supplemental Material, Table S 1.

For the analysis of LDL cholesterol in Sample 3, a total of subjects were included. In the weighted sample, there was a significant difference in sex, race, educational level, family income, marital status, smoking status, alcohol status, BMI, physical function, diabetes, high blood pressure, coronary heart disease, and stroke detailed information can be found in Supplemental Material, Table S 2.

In this study, no association was discovered between low total cholesterol, low HDL cholesterol, low LDL cholesterol and depression in either males or females in a multivariate model that adjusted for potential confounding factors.

This finding was consistent with several previous studies [ 19 , 20 ]. Interestingly, some studies based on the NHANES or other cross-sectional studies have inconsistent conclusions.

The differences in these results may be explained by at least three reasons that are discussed below. First, the differences may be due to sampling error, as there are differences in the included populations in different studies. For instance, Morgan et al.

reported that depression was more common in the low cholesterol subgroup than in the higher cholesterol subgroup in a sample of men aged 70 years or older [ 15 ].

Another case-control study with Mexican major depression patients showed that participants in the healthy control group had a high level of cholesterol 4. One study with middle-aged men reported that the low cholesterol less than 4. Second, the differences may be explained by methodological differences.

On the one hand, the confounding factors included were not the same. Actually, in a study based on the NHANES [ 18 ], the result of the unadjusted model was the same. On the other hand, the difference may be illustrated by the differences in how people were grouped.

In another study, depression was further divided into severe depression and moderate depression, and the intermediate group 4. The results showed that low cholesterol was correlated with a higher risk of severe depression in males but not in males; low cholesterol levels were not correlated with moderate depression in either males or males.

It is believed that compared with normal levels, rather high levels could be more helpful for clinical practice regarding low cholesterol, now that high cholesterol has been proven to be harmful. Third, the potential biological mechanisms should be further discussed.

Cholesterol is an important component of the central nervous system [ 3 , 4 , 5 , 6 ]; however, the majority of cholesterol in the brain is produced by de novo synthesis because of the blood-brain barrier. There was no clear evidence of a relationship between plasma and brain cholesterol levels [ 5 , 29 ].

This means that the association between central nervous system cholesterol and depression is different from that between plasma cholesterol and depression. The specific relationship needs to be further explored.

For the use of lipid-lowering prescription drugs, no difference was found between the depression group and the non-depression group. Notably, proprotein convertase subtilisin-kexin type 9 PSK-9 was found to be a key regulator of LDL cholesterol, and PSK-9 inhibition has shown excellent efficacy in decreasing LDL cholesterol [ 30 ].

The effect of PSK-9 on cognitive function and depression has been recently investigated in several studies [ 24 , 31 ]. However, the NHANES only provided general prescription information for cholesterol, and this article could not determine the relationship between depression and the prescription of PSK-9 inhibitors.

In summary, this study did not support the assumption that low cholesterol was associated with depression. After adjusting for sex, age, race, education level, marital status, BMI, alcohol status, smoking status, self-rated health, poverty income ratio, physical function, comorbidities, and prescription use, no relationship was discovered between low cholesterol and a higher risk of depression in men or women.

This information may contribute to the debate on how to manage people with low cholesterol. Several studies have evaluated the relationship between cholesterol and depression [ 15 , 16 , 17 , 18 , 19 , 20 , 28 ].

Cholesterol levels can be classified as low, normal, or high, and most previous studies combined the normal and high cholesterol groups as a new group for comparison with the low group.

This comparison has some limitations.