The significance of routine
biochemical markers in patients with major depressive disorder
You-Fan Peng , Y ang Xiang & Y e-Sheng Wei
The aim of our study is to examine the levels of routine biochemical markers in patients with major depressive disorder (MDD), and combine multiple biochemical parameters to asss the discriminative power for patients with MDD. We ud the Hamilton Depression (HAMD) score to evaluate the verity of depressive symptoms in 228 patients with MDD. The pha of depression verity was between moderate and vere in MDD patients. There were significant differences between MDD patients and healthy controls in alanine transamina (AL T), urea nitrogen (UN), lactate dehydrogena (LDH), uric acid (UA), total protein (TP), total bile acid (TBA), creatinine (Cr), total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil), high density lipoprotein-cholesterol (HDL-C), fasting blood-gluco (FBG) and fructosamine (SF). Multivariate analysis showed that UN, FBG, HDL-C, SF, TP, Cr and Tbil remained independently association with MDD. Further, a logit equation was established to identify patients with MDD. The composite markers exhibited an area under the curve of 0.810 with cut-off values of 0.410. Our results suggest the associations between UN, FBG, HDL-C, TP, Cr, Tbil, SF and
snow day
MDD, u of the routine biochemical markers in combination may contribute to improve the complete management for patients with MDD.
Depression is a mental dia with global public health concern, especially in developing countries 1. There was evidence that up to 6–12% of the adult population suffered mental disorder and recurrent depression 2. Notable, the etiological rearch of depression has aroud widespread interest in recent years. Among some studies, a plausible association between depressive disorder and glial cell line-derived neurotrophic factor has been well-established by Michel TM 3. In addition, rearchers have speculated that dysregulated immune respon system may be involved with the pathogenesis of major depressive disorder (MDD)4. In another study, oxidative stress has been considered as the physiopathologic mechanism of depressive disorder 5. A recent cross-ctional study found that depression was related to chronic inflammation characterized by elevated C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor (TNF)6. It has been previously obrved that u of TNF inhibitor can alleviate depressive symptoms for treatment-resistant MDD patients with elevated inflammatory markers 7, and the anti-inflammatory medications such as cyclooxygena-2 inhibitor celecoxib exhibited a satis-factory therapeutic effect in patients with MDD 8.
Recently, to diagno neuropsychiatric disorders such as depressive disorder, schizophrenia and bipolar disor-der, proteomic technology has been developed as a uful tool to identify MDD patients 9. Secondly, near-infrared spectroscopy has also been regarded to be a reliably laboratory test for the diagnosis of MDD 10. However, the tools are uncommon and unavailable in the clinical laboratory. Recent studies have shown that veral laboratory markers are associated with systemic inflammation and oxidative stress, such as urea nitrogen (UN), creatinine (Cr), fructosamine (SF) and bilirubin 11,12. Unfortunately, their single u is often limited by poor nsitivity and specificity. Therefore, the aim of our study is to investigate the levels of routine biochemical markers in MDD patients, and combine multiple biochemical biomarkers to estimate the discriminative power for patients with MDD.
Materials and Methods
Laboratory and demographic data were analyzed in 228 patients with MDD, wherein included 43 male and 185 female. The diagnosis of MDD was determined by DSM-IV criteria 13,14. All patients accompanied by
Department of Laboratory Medicine, Affiliated Hospital of Youjiang Medical University for Nationalitie
s, No. 18 Zhongshan Er Road, Bai, Guangxi 533000, China. Correspondence and requests for materials should be addresd to Y .-S.W. (email: yeshengwei_)
Received: 31 May 2016a ccepted: 07 September 2016P ublished: 29 September 2016
OPEN
cardiovascular dia, hypertension, endocrine dia, liver and kidney disorder, gout, infectious dia, met-abolic syndrome, autoimmune dia, malignancy, pregnancy and head trauma history were not included, and any patients with anxiety disorders, neurodegenerative disorders, bipolar or psychotic disorders, mental retar-dation, psychiatric medications u and substance abu were also excluded. We ud the Hamilton Depression (HAMD) score to evaluate the verity of depressive symptoms15, higher scores on the HAMD expresd more vere symptomatology. The following verity range for the HAMD score was ud to classify the depressive symptom verity: mild depression (8–16); moderate depression (17–23); and vere depression (≥24)16.
A total of 251 healthy subjects with healthy diet at least one month were lected as controls, and all healthy individuals were no history of head trauma history, psychiatric disorder, neurological disorder in this study. The study was performed in accordance with the Declaration of Helsinki, and approved
by the Ethics Committee of the Affiliated Hospital of Y oujiang Medical University for Nationalities, and informed connt was obtained from all individuals.
Demographic and clinical data were obtained from diagnostic records. The body mass index was calculated as an individual’s weight in kilograms divided by the square of height in meters. Fasting venous blood from partici-pants were collected to measure biochemical parameters, including alkaline phosphata (ALP), total cholesterol (TC), alanine transamina (ALT), aspertate aminotransfera (AST), UN, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), γ-glutamyl transpeptida (γ-GGT), gluco, lactate dehydrogena (LDH), uric acid (UA), SF, direct bilirubin (Dbil), total bile acid (TBA), total bilirubin (Tbil), total protein (TP), triglyceride (TG), indirect bilirubin (Ibil) and Cr. All biochemical tests were performed by automatic biochemical analyzer.
Statistical analysis. Statistical analys were performed with the statistical package SPSS version 16.0. All continuous variables were expresd as mean (±standard deviation), and categorical variables were expresd as percentage. A significant calculation for sample size was performed by Quanto software. The normality of data was tested with Kolmogorov-Smirnov test. The differences between continuous variables were compared by student t test or Mann-Whitney U test as appropria
te. Demographic data were compared by Chi-square test. We ud stepwi logistic regression analysis to identify underlying biochemical parameters associated with depres-sive disorder. Hosmer-Lemeshow test was also ud to examine an identified effectiveness of model. An identi-fied performance of the combinations of biochemical markers was analyzed by receiver operating characteristic (ROC) curve. P <0.05 was considered statistically significant.
Results
All patients were from Chine Hans population in the identical regions, the mean age of patients with MDD was 39.6 years and 185 (81.1%) were females. Regarding the cumulative clinical profile, the pha of depression verity was between moderate (68.9%) and vere (31.1%) in accordance with HAMD total score (21.7 ±4.12), almost patients suffered from somatic and psychiatric comorbidities, such as pain (56.1%), poor appetite (63.2%), fatigue (37.7%), palpitations (50.0%), insomnia (65.4%), hallucination (42.1%), delusion (37.3%), guilt (26.8%) and psychomotor retardation (24.6%). There were no statistically significant differences in gender, age and body mass index between MDD patients and controls, as shown in Table 1.
Cumulative results for biochemical tests were obtained from patients with MDD and controls. The lab
oratory characteristics were outlined in Table 2. Several significant differences were obrved between the two groups, lower values of ALT, UN, LDH, UA, TP, TBA, Cr, Tbil, Dbil, Ibil were found to be statistical significance in patients with MDD compared with controls. In contrast, the levels of HDL-C, fasting blood-gluco (FBG) and SF were higher in patient with MDD than controls. The other laboratory markers had not significant differences between the two groups.spectating
Statistically significant variables in univariate analysis were considered into stepwi logistic regression analysis, the results of logistic regression analysis showed that UN, FBG, HDL-C, SF, TP, Cr and Tbil remained independently association with MDD (Table 3). Regression coefficients of the biochemical markers were ud to calculate a logit equation for the asssment of patients with MDD as follows: The logarithm of odds =0.511−0.294(UN)+1.537(FBG)+1.009(HDL-C)+2.379(SF)−0.139(TP)−0.108(Tbil)−0.043(Cr). This calculated model was evaluated by using Hosmer-Lemeshow test (P =0.325,Chi-square=9.212).To evaluate the performance of combined biomarkers for patients with MDD, the nsitivity, specificity and area under the curve (AUC) of the markers in combination were calculated, respectively (Table 4). The composite markers exhibited an AUC of 0.810 (95% CI: 0.796–0.846, P <0.001) with the nsitivity of 0.806 and specificity of 0.636, and a cut-off values was defined with 0.410, indicating a more better effectiveness in identifying patients with MDD than all single markers.
Discussion
To this day, there are few objective and available laboratory markers to estimate completely pathological con-ditions in patients with MDD, and single laboratory marker is often the lack of well nsitivity and specificity. Clinical biochemical tests are routine hospital examinations in clinical practice. This investigation found that UN, FBG, HDL-C, SF, TP, Cr and Tbil were independently associated with MDD in logistic regression analysis. Further, our study revealed that u of the markers in combination could provide uful and objective informa-tion in the asssment for patients with MDD.
Oxidative stress derives from incread production of reactive oxygen species, which leads to cell damage by biological reactions such as lipid peroxidation, enzyme inactivation and DNA modification17. Previous studies have demonstrated that oxidative stress related enzymes are associated with the pathogenic process of patients with depression, and anti-oxidative enzymes activity is incread in patients suffering from depressive disor-der18,19. Emerging evidence has suggested that veral inflammatory cytokines such as interleukin-1 (IL-1) beta,
IL-6 and TNF are implicated with oxidative stress in patients with MDD 20,21. Interesting, oxidative s
tress process has also been obrved in the frontal cortex of patients with recurrent depressive disorder 22. Moreover, the xan-thine oxida activity is incread in the thalamus and the putamen of patients with depression, which tends to induce oxidative stress by an incread production of reactive oxygen species 23. The reports provide an impor-tant fact that oxidative stress may be a major contributor in the pathogenesis of MDD. There is no literature available with respect to rum bilirubin levels in patients with MDD, rum bilirubin levels in patients MDD were found to be decread, and lower Tbil concentrations were associated with MDD in the prent study. Bilirubin, the end product of heme catabolism, is an efficient and powerful antioxidant, the role of bilirubin in regarding with oxidation resistance, anti-inflammation and immunosuppression has been demonstrated in various dias 24
. Indeed, lower rum levels of bilirubin have been reported in patients with migraine, carbon
Table 1.
Demographic and clinical characteristics of patients with major depressive disorder and controls.
Table 2. Biochemical parameters between MDD patients and controls in clinical laboratory.
monoxide-poisoned and pulmonary embolism 25–28, and rum bilirubin may provide a protective action in patients with cardiovascular dia and rheumatic dia 29,30. In the studies, bilirubin as an endogenous anti-oxidant may be destroyed by excessive oxidative stress. Thus, the prence of oxidative stress may result in over-consumption of rum bilirubin, which is associated with lower bilirubin in patients with MDD.
Higher levels of HDL-C have been reported in patients with depression 31. In agreement with this finding, incread levels of HDL-C were demonstrated to be associated with MDD patients in our study. In addition, we obrved lower concentrations of UN and TP in patients compared to healthy controls, the findings are consistent with recently reports on MDD patients 32. Serum Cr concentrations were decread in MDD patients compared with controls, the results may attribute to poor appetite and nutrition in patients with MDD, becau accom-panied anorexia has a high prevalent in patients with MDD 33,34. Of note, incread levels of FBG and SF were found to be associated with MDD in our study. Oxidative stress is a crucial player in the establishment of insulin resistance and diabetes mellitus 35. In fact, oxidative stress has been regarded as an underlying mediator of insulin resistance, and there is an inverly relation between oxidative stress and insulin action 36,37. Studies have shown that oxidative stress can decrea insulin nsitivity by GLUT-4 d
eficiency 38. Furthermore, major insulin cre-tion has been found to be dependent on the regulation of intracellular and extracellular reactive oxygen species to a certain extent 39. It has recently been shown that oxidative stress may increa induction of HO-1 expression, leading to insulin resistance and insufficient insulin 35. Obviously, enhanced oxidative stress may result in insulin resistance and influence on insulin cretion in patients with depressive disorder. Nevertheless, elevated FBG and SF have been positively correlated with insulin resistance and insufficient insulin respon in diabetic and non-diabetic patients 40, which are associated with increa in rum FBG and SF concentrations in patients with MDD.
Our study provides an insight on the role of combination markers of UN, FBG, HDL-C, SF, TP , Cr and Tbil in patients with MDD. Specific and nsitive laboratory indexes have been limited in the diagnosis of depressive disorder. In clinical practice, the diagnosis of MDD main depends on physician’s clinical experiences, clinical symptoms and patient’s lf-asssments. In the current study, the biochemical parameters are objective and available, the composite information from the routine biochemical markers may improve the diagnostic effec-tiveness of depressive disorder.
We are aware that this study has veral limitations. First, our study only included Chine Han nationality in this cross-ctional design. Second, the differences of dietary habit might have effect o
n biochemical parameters in different regions and groups, which limit the extrapolation effect of our results. Third, the diagnostic power had to be improved for the logarithm of odds, becau other clinical information was not obtained as variables in multivariate analysis. Taken together, our results suggest the associations between UN, FBG, HDL-C, SF, TP , Cr, Tbil and MDD, u of the biochemical markers in combination may contribute to improve the complete management for patients with MDD. However, our results are needed to be further established with multicenter
and larger-scale study.
Table 3.
Variables associated with MDD patients in logistic regression analysis.
Table 4. Estimated performances of all single markers and combined markers by ROC curve.
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Author Contributions
Y.-F.P. designed the study, arched the literature, analyzed the data, and wrote the manuscript text. Y.-F.P. and Y.X. collected the data and prepared the manuscript. Y.-S.W. confirmed the final version. All authors reviewed the manuscript.
Additional Information
Competing financial interests: The authors declare no competing financial interests.
通关单英文
How to cite this article: Peng, Y.-F. et al. The significance of routine biochemical markers in patients with major depressive disorder. Sci. Rep.6, 34402; doi: 10.1038/srep34402 (2016).
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