Our study investigated the reported prevalence of HL and associated factors in patients with MDD who were hospitalized for the first time. The main results of this study were as follows: (1) The prevalence of HL among patients with first-onset MDD was 72.17%, and 708 met the diagnostic criteria for HL. (2) Among patients with MDD who were hospitalized for the first time, there were significant differences between HL and non-HL subgroups in terms of age at onset, history of suicide, some scaled scores associated with clinical symptoms (including HAMA score, HAMD score, PSS score, CGI-SI score) and metabolism-related parameters (including DBP, SBP, FBG, TSH). (3) HAMD score and CGI-SI score were risk factors for the development of HL in patients with MDD who were hospitalized for the first time. (4) We plotted ROC curves. The area under the ROC curve for the CGI-SI and HAMD score and their combined discriminatory ability of the two factors was approximately 63%, 67%, and 68%, respectively. (5) In MDD patients with co-morbid HL, there was a significant moderate-strength positive correlation between TC and LDL-C levels.
First, we reported the prevalence of combined dyslipidemia among first hospitalized MDD patients was 72.17%, with the prevalence of high TC, high LDL-C, low HDL-C, and high TG accounting for 30.17%, 14.68%, 6.52%, and 57.39% of the total number of first hospitalized MDD patients, respectively. We reported a higher prevalence of HL in patients with MDD than in the Chinese population without MDD or any psychiatric disorder [28]. The higher prevalence of HL in MDD patients than in the average population may be related to the use of antidepressants and antipsychotics or poor lifestyle habits, such as low levels of exercise and unhealthy diet, in MDD patients [29, 30]. A national study on the correlates of HL among first-treatment MDD patients showed that the proportion of MDD patients with co-morbid HL was 61% (1048/1718) [31], which is lower than the 72.17% we reported. However, more than half of the population in our study (64.8%) had a history of outpatient treatment, and the use of medication may explain the different prevalence of HL we reported [32]. Our definition of dyslipidemia was also more stringent, so more patients were included in the non-HL subgroup.
Regarding foreign studies, to our knowledge, current data reporting the prevalence of HL in the MDD population are incomplete. A retrospective study from the United Kingdom reported a prevalence of 41.6% for high TG and 34.2% for low HDL-C in depressed patients [33], and the prevalence of high TG was generally consistent with that reported in the German study (43.1%) [34]. Although there is heterogeneity in the current relevant studies, the reasons for these heterogeneities may be related to demographics, age, and sociocultural characteristics. However, they largely support our finding that the prevalence of HL is higher in patients with MDD.
Second, our study showed significant differences between the HL subgroup and the non-HL subgroup on several clinical symptom scales (HAMD, HAMA, CGI-SI, PSS), metabolism-related indicators (FBG, SBP, DBP, TSH), presence of a history of suicide, and age at onset. Existing studies have shown that patients with combined lipid metabolism have higher HAMD scores, HAMA scores, PSS scores, and TSH levels than patients with MDD without combined abnormal lipid metabolism [35]. Patients with MDD with or without HL also exhibit variability in metabolic indicators. Previous studies have shown a biphasic relationship between depression and metabolism, with an increased risk of HL, hypertension, and hyperglycemia in MDD patients [36, 37]. It may be associated with increased central and peripheral activation of the immunometabolic or endocrine system [38, 39]. A study of lipid disorders and suicide risk showed an increased risk of suicide attempts in MDD patients with HL [40]. The biological mechanisms underlying the association between lipid profile and suicide in MDD patients remain unclear; the possible influence of lipid profile on the 5-hydroxytryptamine system may play an important role [41]. Studies on the effect of age at onset on lipids in MDD patients are scarce, and in available research, we found that depressed patients with childhood onset showed higher TG levels and lower HDL-C levels [42].
Third, we reported two risk factors: the HAMD and CGI-SI score, which implied that HL was more likely to occur in MDD patients with severe clinical symptoms, consistent with previous studies [43, 44]. However, the relationship between depression and metabolism may be bidirectional, as a longitudinal study in Finland found that a pattern of sharply elevated triglyceride levels throughout childhood and early adulthood may be associated with an increased risk of depressive symptoms in adulthood [45]. Furthermore, numerous studies support that more disturbed metabolic indicators appear to be associated with depression severity in depressed patients [16, 46, 47]. One study found that TNF-alpha and cytosolic interleukin (I)-6 transcriptional signaling may be increased in patients with refractory depression, implying that lipid peroxidation may inhibit therapeutic response in depressed patients [48]. Interestingly, in another study, infliximab improved treatment response and HL in patients with refractory depression by inhibiting TNE signaling, and the reduction of inflammation has a positive role in driving both lipid metabolism and clinical symptomatic improvement in depressed patients [49], i.e., inflammation may be a common pathomechanism for both.
In addition, we plotted ROC curves. The area under the ROC curve for the CGI-SI and HAMD score and the combined discriminatory power of these factors were approximately 63%, 67%, and 68%, respectively, which implies that the severity of the patient’s condition and the severity of the depressive symptoms have some diagnostic power for the presence of HL in patients with MDD.
Finally, we investigated the relationship between different lipid parameters in MDD patients with HL. We found a significant and moderately strong positive correlation between TC and LDL-C. Considering that LDL-C is a part of TC, we speculated that LDL-C may more closely influence elevated TC in patients with MDD. Between the other types of lipid parameters, we did not find significant correlations or the correlations were so weak that they might not be of practical significance.
There are several limitations to our study. First, as a cross-sectional study, we could not determine the causal relationship between abnormal lipid metabolism and various factors. Second, although our sample included only Chinese people, our findings may not be generalizable and may not apply to populations in other countries due to differences in sociodemographic characteristics. Third, our sample consisted mainly of patients with an urgent need for hospitalization, usually in the acute phase of the disease. Therefore, our findings do not apply to patients with stable MDD. In addition, we could not exclude the effects of confounding factors, such as the effects of patients’ diet, alcohol consumption, and physical activity on lipids. The use of antidepressants also added to the study’s confounding factors, considering that 64.8% of our sample had a history of outpatient treatment. Finally, to minimize the impact of the intervention effect on the study results and more accurately assess the impact of other potential factors on lipids in patients with MDD, we chose to exclude patients who had received lipid-lowering therapy. However, this may also have led to an underestimation of the prevalence of co-morbid HL in MDD in our study. To remedy the shortcomings of the current study, we plan to conduct a more in-depth prospective study in future studies.
In conclusion, this study demonstrated a high prevalence of HL in first-time hospitalized MDD patients. Higher HAMD and CGI-SI scores were risk factors for the development of HL in MDD patients, and HAMD and CGI-SI scores predicted the severity of HL. These results suggest that timely improvement of the clinical status of at-risk individuals may help reduce their risk of developing dyslipidemia. It also implies that the presence of HL may indicate more severe depressive symptoms in patients with MDD. However, due to individual differences (including other health problems, lifestyle, genetic risk, etc.), the use of a fixed threshold to define HL may not accurately reflect the actual risk profile of patients with MDD. Therefore, clinicians need to evaluate patients carefully on a case-by-case basis. In addition, clinicians should pay close attention to lipid metabolism in patients with major depression. Given the interaction between depressive symptoms and HL, lipid-lowering therapy should be initiated immediately in patients with significant depression who meet the diagnostic criteria for HL.