Prevalence and factors associated with metabolic syndrome in first hospitalization for major depression disorder patients

Major depressive disorder (MDD) is a common and socially burdensome psychiatric disorder with a causal and complex relationship with metabolic syndrome (MetS), which is often co-morbid. However, the prevalence and risk factors for MetS in patients with MDD are inconclusive. The purpose of this study is to investigate the prevalence and factors influencing MetS in first hospitalization MDD patients. A total of 981 MDD patients were included. Sociodemographic and general clinical data were collected from the patients, while metabolism-related parameters were also measured, and psychological symptoms were assessed. Our study found that the prevalence of MetS in the study population was 9.68%. MDD patients with MetS had higher levels of metabolism-related parameters and more severe psychological symptoms. We identified risk factors for MetS and its severity separately: age of onset of MDD, more severe depressive symptoms, and higher thyroid stimulating hormone (TSH) levels were risk factors for the development of MetS, whereas higher TSH levels were risk factors for the severity of MetS. Our results suggest that MetS is not highly prevalent in MDD patients, but certain risk factors may increase its likelihood and severity, and that these findings could be beneficial for clinical intervention and care of MetS.

Major Depressive Disorder (MDD) is one of the most debilitating chronic mental illnesses 1 , with a 12-month prevalence of about 6% in the population 2 .The life expectancy of people diagnosed with depression is estimated to be shortened by 10-14 years 3 .However, the cause of MDD remains largely unknown, and relapse rates for the disorder remain high 4 .There are indications of a complex relationship between MDD and metabolic syndrome (MetS) that is mutually reinforcing and mutually causal.On the one hand, MDD alters the patient's gut microbiota through the regulatory mechanism of the microbiota-gut-brain axis, which ultimately leads to the development of metabolic disorders such as obesity 5,6 .On the other hand, MetS was found to share genetics and possible risk gene pathways with MDD 7,8 .This implies that MetS may be the native disease of MDD.Clinical studies have also confirmed an increased prevalence of MetS and an increased risk of elevated levels of some metabolic parameters in patients with MDD 9,10 , while the prevalence of depressive disorders in patients with metabolic disorders is equally surprising 11,12 .
The MetS is characterized by the presence of central obesity, hypertension, low levels of high-density lipoprotein cholesterol (HDL-C), elevated triglyceride (TG) levels, and hyperglycemia 13,14 .It is a well-established collection of risk factors for cardiovascular disease (CVD) 15,16 .Consequently, the identification and assessment of MetS risk factors in patients diagnosed with MDD, a population at high risk for MetS, is crucial in clinical practice.In fact, in-depth research on MetS-related studies in MDD populations has been one of the major areas of interest for researchers and psychiatrists.In addition to reporting that MDD and MetS or its components share a common genetic pathway 7,8,17 , researchers have identified important implications of MetS or its components for the MDD population.For example, fasting blood glucose (FBG) levels and HDL-C levels are potential markers used to predict suicide in young MDD patients 18 , low plasma total cholesterol (TC) levels are associated with recent suicide attempts in MDD patients 19 , and TC levels play an important role in the pathophysiology of MDD 20 .All of this informs us of the need for further clarification and understanding of the prevalence and correlates of MetS in the confirmed MDD population.
Although the prevalence of MetS in populations with MDD is currently being addressed by researchers who have reported a high degree of heterogeneity ranging from 20.2 to 45.2% [21][22][23][24][25][26] , none of these studies have concentrated on the severity of MetS.The objective of this study was to investigate the prevalence of MetS and its associated factors in a larger sample of first hospitalized MDD patients in China.Specifically, we aimed to examine the factors related to the severity of MetS.

Results
The differences between clinical subgroups with and without MetS.Out of all the MDD patients included in the study, 94 met the diagnostic criteria for MetS, representing 9.68% (95/981) of the total.There were significant differences in demographic and general clinical data between the subgroups with and without MetS.Specifically, as illustrated in A binary logistic regression model (Backward: Wald) was constructed with the variables that differed in the univariate analysis as independent variables and MetS as the outcome variable.The results showed that onset age (B = 0.06, p < 0.001, OR = 1.06),HAMD scores (B = 0.12, p = 0.011, OR = 1.12), and TSH (B = 0.36, p < 0.001, OR = 1.44) were risk factors for MetS (Table 2).Moreover, AUCROC revealed the following values for each risk factor: onset age was 0.74, HAMD was 0.69, and TSH was 0.78.To identify MetS from non-MetS, the combination of onset age, HAMD score, and TSH produced a higher AUC value of 0.87 (p < 0.001, 95%CI = 0.83-0.90)(Fig. 1).
Influencing factors of MetS scores in MDD patients: a multiple linear regression model.Finally, we construct a multiple linear regression model (Input) with MetS as the outcome variable and the relevant factors affecting MetS in the previous step as the dependent variables.The results showed that TSH (B = 0.03, t = 3.23, p = 0 0.002, 95%CI 0.01-0.02)was risk factors for higher MetS scores (Table 3).

Discussion
To the best of our knowledge, this is the only study that reports factors related to the severity of MetS in MDD patients in Chian.The main findings of our study are as follows: 1.The prevalence of MetS in the included group was 9.68%.2. Compared to the non-MetS subgroup, the MetS subgroup had not only higher levels of a wide range of metabolic parameters, but also more severe psychopathological and psychological symptoms, such as scores on the four scales of PSS, HAMD, HAMA, and CGI-SI, and higher age and onset age of the patients.3. Onset age, HAMD scores, and TSH levels were risk factors for the diagnosis of MetS. 4. The levels of TSH was risk factor for higher MetS scores.Several factors contribute to the substantial heterogeneity in the prevalence of MetS among individuals diagnosed with MDD, including variations in ethnicity 27 , geography 10 , and distinct diagnostic criteria for MetS 13,28 .In our study, we reported a MetS prevalence of 9.68% among MDD patients, which is significantly lower than the figures observed in similar research.Focusing solely on the East Asian population, a small sample from Taiwan, China, showed a 34.3% prevalence of MetS 21 , while a large sample from Japan indicated a 14.0% prevalence 29 .Although the MetS prevalence reported in these two studies differs greatly, both percentages were notably higher than those documented in our research.Upon comparison, we discovered that both studies used the same diagnostic criteria for MetS, but their criteria were more stringent than ours, which may account for the marked difference in reported prevalence.In contrast, a recently published national epidemiological survey from China reported a standardized prevalence of MetS of 31.1% among the general adult population in China 30 .This prevalence is roughly comparable to that reported in Taiwan, China, which has the highest prevalence of MetS in MDD patients 21 .In conclusion, we determined that the prevalence of MetS was relatively low among first-time hospitalized MDD patients in China.
MDD is often regarded as an independent risk factor for MetS 31 , primarily due to the shared genetic risk pathway between the two conditions 7 .However, does this imply that increased severity of depressive symptoms correlates to a higher risk of MetS diagnosis?Several studies have provided affirmative answers to this question 22,32,33 , consistent with our findings.Another study reported a positive correlation in females, but an inverse relationship in males 34 .Further research indicated that the severity of depressive symptoms is associated with specific components of MetS, such as elevated blood glucose levels, higher TG levels, lower HDL-C levels, and increased WC 35,36 .Generally, both MDD and depressive symptom severity are important independent risk factors for MetS comorbidity in MDD patients.Higher TSH levels have previously been identified as significant risk factors for MetS in non-MDD populations 37,38 , and our study expands the range of populations for which these findings apply.Additionally, we report that increased onset age of MDD is the third risk factor for MetS diagnosis in MDD patients.While we have not found similar reports to date, age is a crucial contributor to MetS diagnosis in the general population 30 , and MDD itself is a risk factor for MetS 31 .Consequently, we consider the age of MDD onset as a specific result of the dual influence of age and MDD on MetS.In further ROC analysis, we determined that the triad of onset age of MDD, HAMD scores and TSH levels had good combination diagnostic capability for MetS.
Finally, we report higher TSH levels as a factor influencing the severity of MetS.Up to now, there are relatively few studies on factors related to the severity of MetS in the MDD population.The limited number of studies have reported a large heterogeneity of study objectives or outcomes.For example, one study prospective study reported a significant prospective association between initial depressive symptoms and subsequent MetS scores among clergy 39 .Another study found that in the African American female population, higher depressive symptom scores were associated with higher MetS severity in women 40 .Unfortunately, in the present study our findings differ from the two aforementioned studies in that we report no significant effect of the severity of depressive symptoms on the severity of MetS.Whether the reason for this is due to ethnicity, geography or sampling error needs to be further investigated and verified in the future.As mentioned earlier, TSH is an important risk factor for MetS even in the MDD population.Studies have shown that the development of MetS 41,42 , and related parameters of MetS, such as weight gain 43 , are positively correlated with TSH levels.It has also been reported that the prevalence of MetS, abdominal obesity and hypertriglyceridemia is higher in subjects with clinical hypothyroidism 44 .Although none of these studies are direct evidence that higher TSH levels are a risk factor for MetS severity, they are certainly the strongest supporting evidence.
The present study also has several limitations.First, as a cross-sectional study, our results cannot clarify the causal relationship between MetS, its severity and influencing factors.This requires further prospective studies.Second, our sample consisted of patients in the acute phase requiring hospitalization, so our findings may not be generalizable to MDD patients in the symptom-stable phase.Third, our sample included both drug-naive samples and samples with a history of outpatient treatment, which increased the confounding factors of this study, and we will report separately on the effect of antidepressant exposure on the results.Fourth, due to the relatively small number of MetS subgroup cases we actually obtained, this may lead to limitations in the further generalization of the results obtained from our regression analysis, larger sample sizes may be beneficial in addressing this issue.In the future, we will try to properly control for the above shortcomings.
In conclusion, the prevalence of MetS in MDD patients is relatively low.Risk factors for MetS include early onset of MDD, more severe depressive symptoms, and elevated levels of TSH.Moreover, higher TSH levels also contribute to the severity of MetS.Identification of these risk factors has proven valuable for psychiatrists in the evaluation and detection of MetS and its severity in patients with MDD during their initial hospitalization.This knowledge helps in guiding interventions and implementing appropriate care measures.

Figure 1 .
Figure 1.The discriminatory capacity of related factors for distinguishing between patients with and without MetS in MDD patients.The area under the curve of onset age, HAMD score, TSH, and the combination of these three factors were 0.74, 0.69, 0.78, and 0.87, respectively.
https://doi.org/10.1038/s41598-023-42720-ywww.nature.com/scientificreports/ the discriminatory capacity of significant parameters to distinguish between patients with and without MetS.Finally, a multiple linear regression model was constructed with the MetS score as the outcome variable and the factors influencing MetS in binary logistic regression as the independent variables to determine the factors influencing the severity of MetS.All p values were 2-tailed, and the significance level was < 0.05.Statistical analyses were performed using SPSS 27 (SPSS, Inc., Chicago, IL).

Table 1 ,
the MetS subgroup exhibited higher values in various indicators, including age, onset age, percentage of unmarried individuals, prevalence of suicidal behavior, MetS scores,

Table 1 .
The demographic and general clinical data in different clinical subgroups.PSS: C: low density lipoprotein cholesterol; BMI: Body mass index.*p < 0.05.

factors of MetS in MDD patients: based on binary logistic model.
Next, we focused on the factors influencing MetS in MDD patients.