RESEARCH ARTICLE |
https://doi.org/10.5005/jp-journals-10028-1655 |
Lipid Profile and Total Antioxidant Status in Major Depressive Disorder Patients in North Indian Tertiary Care Hospital: A Case Control Study
1,2,4Department of Biochemistry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
3Department of Psychiatry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Corresponding Author: Sant Ram, Department of Biochemistry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, Phone: +917508925668, e-mail: drsantram2016@gmail.com
Received: 24 August 2023; Accepted: 18 December 2023; Published on: 06 February 2024
ABSTRACT
Aims and background: Major depressive disorder (MDD) is the most common mental health disorder. It is a multifactorial disease and the pathophysiology is not clear, which results in fewer available options for treatment and more treatment-resistant cases. The development of early diagnostic and prognostic markers will help in the reduction of the burden of this disease. Oxidative stress plays an important role in depression and it is evident that antioxidant effects are exerted by many treatment modalities available for depression. Lipids have a role in inter- and intraneuronal functions of the brain, they can also be developed as markers for MDD.
Materials and methods: In this study, we compared serum antioxidant status and serum lipid profile in MDD patients and healthy controls. A total of 30 MDD patients and 30 healthy controls were included in the study. Serum antioxidant level and serum lipid profile were done using a kit-based method on an autoanalyzer.
Results: The level of antioxidants [mean ± standard deviation (SD)] in controls was 1.332 ± 0.215 mmol/L and in MDD patients was 1.399 ± 0.298 mmol/L, the difference was not significant. The level of total cholesterol in controls was 169.203 ± 31.114 mg/dL and in MDD patients was 193.080 ± 38.876 mg/dL, the difference was statistically significant (p = 0.011). The difference in low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) levels was insignificant between healthy controls and MDD patients.
Conclusion: Mixed findings from our study and the various literature suggest that there is a complex association between MDD, antioxidants, and lipid profile, and extensive study is needed in the field.
Clinical significance: The study will be helpful in finding biomarkers for MDD.
How to cite this article: Pathak P, Kaur S, Grover S, et al. Lipid Profile and Total Antioxidant Status in Major Depressive Disorder Patients in North Indian Tertiary Care Hospital: A Case Control Study. J Postgrad Med Edu Res 2024;58(1):19–23.
Source of support: Nil
Conflict of interest: None
Keywords: Antioxidants, Cholesterol, Lipid profile, Major depressive disorder, Triglycerides.
INTRODUCTION
Depression is the most common mental health disorder affecting 3.8% of the world’s population which corresponds to 280 million people worldwide.1 Major depressive disorder (MDD) is a multifactorial disease and its pathophysiology involves genetic as well as environmental factors.2 The burden of depression increased significantly after the coronavirus disease 2019 (COVID-19) pandemic. The reason behind this increase could be the increased stress in the general population worldwide or because of the higher oxidative stress in the patients suffering from COVID-19.3 To date, the available treatment options for depression are antidepressant drugs (ADs), electroconvulsive therapy (ECT), and psychotherapy.4 Despite a lot of research in the field of biomarkers for psychiatric illnesses, there are very few established biomarkers, and most of them are not in current clinical practices.5
Oxidative stress plays an important role in unipolar depression.6 Oxidative stress and antioxidant defense biomarkers including, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), isoprostanes, superoxide dismutase (SOD), and glutathione levels are found to be associated with depression.7 These biomarkers are also associated with the treatment of depression and can be used for the prediction of response to the treatment in MDD patients.7 MDD has been characterized by lower key antioxidants and higher levels of reactive oxygen species (ROS) and reactive nitrogen species.8
The inter- and intraneuronal function in the brain is influenced by the changes in brain lipid concentration and the association of MDD is well known to be associated with dyslipidemia and obesity. Moreover, there is a role of lipid biomarkers in the pathophysiology of MDD.9 Cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels have been shown to have an association with treatment-resistant depression.9 As lipid biomarkers are easy to measure and lipids have a role in inflammation and many inflammation-associated diseases. In addition, the latest studies have shown that pathophysiology of depression involves neuroinflammation. Lipid levels in the blood can have the potential to become markers for the diagnosis of depression as well as for the prediction of the response in MDD patients.10 With this background, we planned to study the status of serum antioxidant levels and serum lipid profiles in MDD patients.
MATERIALS AND METHODS
Institutional Ethics Committee (IEC), Postgraduate Institute of Medical Education and Research (PGIMER) Chandigarh permitted the current study (IEC number: NK/5018/MD/352). The ethical standards of the relevant national and institutional committees on human experimentation and the Helsinki Declaration of 1975, as revised in 2008, had been considered in the study.
All the participants included in the study had ages>18 years. The Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5) has been used for the diagnosis of MDD and the assessments were made by a qualified psychiatrist.
The total number of participants recruited for the study was 60. Participants included 30 patients, diagnosed clinically as MDD based on DSM-5, taking outpatient services in the department of psychiatry, and 30 healthy individuals without any personal or family history of psychiatric illness.
Patients with history of any other psychiatric disorders such as bipolar disorder or schizophrenia, and patients of MDD taken more than one antidepressant medication before enrolment were not included in the study.
Venous blood samples (5 mL) of all patients and controls were collected in plain Greiner Bio-One vials (Ref number 454092) with aseptic precautions in the morning after overnight fasting.
The serum antioxidant level was estimated using RANDOX TOTAL ANTIOXIDANT STATUS Kit (Reference number NX 2332) on an autoanalyzer (Beckman Coulter AU 5800) according to the manufacturer’s protocol. The assay is based on the production of radical cation ABTS® [2,2’-Azino-di-(3-ethylbenzothiazoline sulfonate)]. ABTS® is incubated with peroxidase (metmyoglobin) and H2O2 to produce the radical cation ABTS®. This has a relatively stable blue-green color, which is measured at 600 nm. Antioxidants in the added sample cause suppression of this color production to a degree that is proportional to their concentration.
The serum cholesterol was estimated using Roche COBAS c 701/702 (COBAS 8000) autoanalyzer. The assay was based on the enzymatic colorimetric method.
The serum LDL was estimated using Roche COBAS c 701/702 (COBAS 8000) autoanalyzer. The assay was based on the homogenous enzymatic colorimetric method.
The serum HDL was estimated using Roche COBAS c 701/702 (COBAS 8000) autoanalyzer. The assay was based on the enzymatic colorimetric method.
The serum triglyceride (TG) was estimated using Roche COBAS c 701/702 (COBAS 8000) autoanalyzer. The assay was based on the enzymatic colorimetric method.
Reference ranges of different parameters are mentioned in Table 1.
| S. No. | Parameter | Reference range |
|---|---|---|
| 1 | Antioxidants | 1.3–1.77 mmol/L |
| 2 | Cholesterol | <200 mg/dL |
| 3 | LDL | <100 mg/dL |
| 4 | HDL | 40–60 mg/dL |
| 5 | TG | <200 mg/dL |
The data analyses were done using Statistical Package for the Social Sciences (SPSS) 27.0 (SPSS, IBM, United States) and GraphPad Prism 9.2.0 software. To examine group differences, Chi-squared and independent t-tests were used for categorical variables and continuous variables, respectively. Continuous variables were expressed as mean and standard deviation (SD). Categorical variables are described as frequency and percentages. For non-normally distributed continuous variables, Mann−Whitney U tests were used to compare groups. A p-value of <0.05 was considered to be statistically significant.
RESULTS
Antioxidants in Major Depressive Disorder
The level of antioxidants (mean ± SD) in controls was 1.332 ± 0.215 mmol/L and in MDD patients was 1.399 ± 0.298 mmol/L. The difference was not significant with a p-value of 0.32 (Fig. 1).
Fig. 1: Level of antioxidants in healthy controls and MDD patients
Lipid Profile in Major Depressive Disorder
The level of total cholesterol (mean ± SD) in controls was 169.203 ± 31.114 mg/dL and in MDD patients was 193.080 ± 38.876 mg/dL. The difference was statistically significant with a p-value of 0.011 (Fig. 2A).
Figs 2A to D: Lipid profile analysis in healthy controls and MDD patients: (A) Total cholesterol; (B) LDL cholesterol; (C) HDL cholesterol; (D) TG
The level of LDL (mean ± SD) in controls was 93.563 ± 25.722 mg/dL and in MDD patients was 106.230 ± 31.073 mg/dL. The difference was statistically not significant with a p-value of 0.91 (Fig. 2B).
The level of HDL (mean ± SD) in controls was 45.530 ± 11.905 mg/dL and in MDD patients was 47.477 ± 13.871 mg/dL. The difference was statistically not significant with a p-value of 0.562 (Fig. 2C).
The level of TG (mean ± SD) in controls was 130.380 ± 54.916 mg/dL and in MDD patients was 167 ± 89.707 mg/dL. The difference was statistically not significant with a p-value of 0.059 (Fig. 2D).
DISCUSSION
As of now the diagnosis in the psychiatric clinics is mainly based on patient interviews and questionnaires and the same is used for deciding the treatment. The search for biomarkers can aid in more accurate diagnosis and treatment response prediction. Hence, we aimed to study the potential value of antioxidant status and lipid profile as possible future biomarkers for the diagnosis of MDD. The experimental groups consisted of 30 patients and 30 healthy subjects.
To our knowledge, this is the first study to investigate the association between the serum level of antioxidants and lipid profile with MDD in our North Indian population.
In our study, no significant difference was observed in the total antioxidant status of MDD patients and healthy controls. Our findings are at odds with the vast majority of the studies where different authors have reported that total-oxidant status is decreased in the case of MDD patients and oxidative stress is increased. Additionally, A meta-analysis study has also linked depression with increased oxidative stress and lower antioxidant status.11,12 According to certain theories, oxidative stress may be involved in the pathogenesis of several neuropsychiatric diseases including MDD. When ROS are present in excess and anti-oxidants are not enough to neutralize the stress caused by these species, ROS may react with macromolecules of the cell such as fatty acid, deoxyribonucleic acid (DNA), etc., thereby causing damage to these molecules. The brain is one of the organs most susceptible to these harmful consequences because of its high metabolic rate.11
Although the general idea is that MDD is associated with oxidative stress, similar to ours, various studies have fueled the disparities. The patient’s total antioxidant status was reported to be increased.13 Sofic et al. reported no significant difference in antioxidant capacity between depressive patients and controls, which is consistent with the findings of our investigation.14 In another study, depressed females did not significantly vary from the control group in terms of their overall antioxidant status.15 Similarly, the antioxidant enzyme SOD has shown inconsistent results. Bajpai et al. found lower levels of SOD in MDD patients whereas Jordan et al. found increased SOD levels.11,16 Studies examining different markers of oxidative stress such as MDA, and 8-hydroxy-2’deoxyguanosine (a marker of oxidative DNA damage) have also discovered discrepancies in the levels of these markers when compared with the control group.16,17
Antioxidant activity has also been investigated by some studies concerning the treatment of MDD, and they discovered a rise in total antioxidant activity among treatment-responsive individuals after treatment with oral antidepressants.13
It is clear from the above facts and the studies that there is a need to evaluate the exact relationship of oxidative stress with depression.
Over the past 3 decades, there have been numerous reports indicating a connection between depression and dyslipidemia. Twenty percent of the body’s total cholesterol is located in the human brain, 20% of which is present in the oligodendrocytes that produce myelin. There have been observations of myelination and oligodendrocyte malfunction in many mental diseases, particularly MDD. The presence of cholesterol can affect membrane fluidity, which in turn affects synaptic transmission, hence directly influencing the occurrence of depression.18
According to the results of our study, depression is linked to significantly higher cholesterol levels in MDD patients than in healthy controls. Our findings are in agreement with several other pieces of research that found a direct correlation between cholesterol levels and depressive symptoms.19,21 Some researchers have even confirmed the association between hypercholesterolemia and treatment resistance in MDD.22 Increased total cholesterol is a risk factor for cardiovascular diseases and various pieces of evidence have also shown that patients with MDD are at a higher risk of developing cardiovascular disease.23,24 On the other hand, some studies have shown findings that do not agree with ours, total cholesterol levels were shown to be reduced in depressed patients.13,18,23
We discovered no statistically significant difference in the levels of HDL and LDL cholesterol and TG in our study. A recent study by Bharti et al. reported that both HDL and LDL did not significantly differ in MDD patients and healthy controls. Similar to total cholesterol, its subtypes have shown inconsistent results. Some authors have noted increased HDL levels,19 while others have reported decreased HDL levels in the case of MDD patients.25 According to some studies depression is associated with increased LDL values.20,21
The cholesterol level in our study has been found significantly different in the healthy group and MDD patients’ group while the other parameters of lipid profile are not significantly different in both groups, similar to results shown in other studies.26 The role of cholesterol is very important in maintaining the structure and function of the central nervous system (CNS) cells including neurons, microglia, and astrocytes by regulating the fluidity of biomembranes and synaptic transmission, and not limited to the systemic role of transporting lipids among the different tissues,27 which might be the reason for the different results for cholesterol, LDL, and HDL in our study subjects.
The majority of the previous studies have reported higher TG levels15 and some studies have inconsistent results and reported lower TG levels in MDD patients.18,25 A meta-analysis has also associated lower TG levels with increased suicidality.17
These mixed findings reflect the complexity of the possible association between MDD and the lipid profile of patients. Thus, such inconsistent results correspond to the need for extensive case-control and mechanistic studies to decipher this association. Studies to find out the relationship between lipid levels with treatment response are also required and we suggest that lipid level measurements should be a part of the routine for MDD patients at their first visit with regular measurements during follow-up with response to treatment in MDD patients.
CONCLUSION
We concluded that serum antioxidant level is not significantly related to MDD in our study. Higher cholesterol level is associated with MDD while the levels of LDL, HDL, and TG in serum are not significantly associated with MDD.
Inconsistent findings in different studies all over the world show the requirement for more large-scale studies on the relation between MDD, antioxidants, and lipid profile.
The limitation of our study is that the sample size of this study is very small.
The heterogenicity of this case-control study was limited because the origin of all the participants was from North India.
Clinical Significance
Major depressive disorder (MDD) is the most common disorder worldwide and the study helps establish a connection between MDD with antioxidant status and lipid profile in the serum. Findings may create a new path for future researchers to connect the dots and develop some easy biomarkers for MDD, which will be helpful in both early diagnosis and treatment of the disease.
ORCID
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