|Year : 2020 | Volume
| Issue : 1 | Page : 15-19
A study on serum lipid parameters in individuals with major depressive disorder in comparison to normal controls
Bilal Ahmad Bhat, Shabir Ahmad Dar, Arshad Hussain
Department of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir, India
|Date of Submission||09-Jul-2019|
|Date of Decision||30-Nov-2019|
|Date of Acceptance||24-Feb-2020|
|Date of Web Publication||08-Jul-2020|
Dr. Bilal Ahmad Bhat
Department of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
BACKGROUND: Evidence seems to suggest that dysfunction in many biological functions is associated with major depressive disorder (MDD). Literature suggests a possible link between different lipid parameters and depression.
AIMS: The aim was to study lipid parameters in persons diagnosed with MDD and to find a correlation between these lipid parameters and depression.
SETTINGS AND DESIGN: This was a case–control study conducted in outpatient services of the psychiatry department.
MATERIALS AND METHODS: A total of 100 subjects were included in this study. Fifty drug-naïve depression cases as assessed clinically and with Hamilton Rating Scale for depression were included in the study group, while the control group comprised 50 normal controls. Lipid parameters were obtained from fasting blood samples in both the groups.
STATISTICAL ANALYSIS: Data analysis was performed using SPSS 16. Continuous variables and categorical variables were summarized, respectively, as mean and standard deviation and frequency and percentage.
RESULTS: The mean serum total cholesterol (TC) and mean serum low-density lipoprotein cholesterol (LDL-C) in the study group were significantly low in comparison to the control group. There was a significant negative correlation with serum TC (r = −0.710; P = 0.0001), mean serum LDL-C (r = −0.608; P = 0.0001), and triglycerides (TGs) (r = −0.289; P = 0.042).
CONCLUSIONS: Drug-naïve Individuals with MDD had significantly low TC and LDL-C in comparison to normal individuals. A significantly negative correlation was there between the severity of depression and TC, LDL-C, and TG.
Keywords: Lipid parameters, major depressive disorder, total cholesterol
|How to cite this article:|
Bhat BA, Dar SA, Hussain A. A study on serum lipid parameters in individuals with major depressive disorder in comparison to normal controls. BLDE Univ J Health Sci 2020;5:15-9
|How to cite this URL:|
Bhat BA, Dar SA, Hussain A. A study on serum lipid parameters in individuals with major depressive disorder in comparison to normal controls. BLDE Univ J Health Sci [serial online] 2020 [cited 2020 Sep 30];5:15-9. Available from: http://www.bldeujournalhs.in/text.asp?2020/5/1/15/289196
Worldwide, major depressive disorder (MDD) is one of the leading causes of disability with more than 300 people affected by this disorder globally, and it contributes a major portion to the overall global burden of disease. With moderate-to-severe intensity and its long-lasting course, it can cause a serious health problem in the sufferer, and at its worst, can lead to suicide. Evidence seems to suggest that dysfunction in many biological functions is associated with MDD. An apparently independent increase in the death of patients on lipid-lowering drugs due to suicides, accidents, and homicidal violence prompted several researchers to focus on a potential link between low serum lipid levels and MDD and suicide., In routine clinical practice, basic lipid parameters used in cardiovascular risk identification include total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). However, there is a lack of well-documented evidence for these lipid parameters as laboratory biomarkers to be predictive of depression. In the current literature, contradictory findings exist with regard to a possible link between depression and these lipid parameters. Various previous studies have found lower TC in patients with MDD in comparison to controls.,, Other studies indicate that higher levels of TC might be related to depression., Similarly, extensive assessment of other lipid parameters in various studies gave inconsistent findings.,, Further, some studies have found that an effective treatment of depression with pharmacotherapy modulates some of these altered lipid parameters., Whether this is primarily the effect of antidepressants or due to amelioration of depressive symptoms is not clear. With this complex association between MDD and serum lipid parameters, there is a need to further explore this association. Therefore, we planned to conduct a study to compare serum lipid parameters of treatment naïve MDD patients with normal controls.
| Materials and Methods|| |
This study was conducted on patients visiting outpatient service of the Department of Psychiatry, Government Medical College, Srinagar, in January 2019. Fifty normal weight drug-naivefirst episode depression patients of age 18–60 years diagnosed as per the International classification of diseases, diagnostic criteria for research, tenth revision (ICD-10-DCR) were included in this study. A group of 50 normal weight age and gender-matched healthy individuals who have a score of <2 on General Health Questionnaire and were without any current psychiatric diagnosis were also selected, using a nonprobability purposive sampling, during the same time period as a control group for comparison. Written and informed consent was obtained from all the individuals included in our study in an easily understandable language. Approval was obtained from the ethics committee of our institute. Those individuals, from both cases and controls, with other major psychiatric diagnosis, with known chronic medical or surgical illness, with history of dyslipidemia, on treatment for dyslipidemia, on oral contraceptives, with body mass index (BMI) below 18.5 kg/m2 or above 25 kg/m2, and not falling in age group of 18–60 years were excluded from the study. Sociodemographic data and clinical details were recorded. The diagnosis was made clinically as per the ICD-10-DCR. To assess the severity of depression, Hamilton Depression Rating Scale (HAM-D) was used. The height and weight of the patients were measured to calculate BMI using the formula: BMI = weight/height 2 (kg/m2). A fasting blood sample was taken to estimate TC, HDL-C, LDL-C, and TG levels in both the groups. Data analysis was performed using SPSS version 16 (IBM, Armonk, NY, USA). Continuous variables were summarized as mean and standard deviation, whereas categorical variables were summarized as frequency and percentage. Means between the two groups were compared by independent samples t-test. To calculate the correlation between the severity of depression and different lipid parameters in the study group, Pearson's correlation coefficient was used. P value significance was set at <0.05.
| Results|| |
The mean age in the study group was 39.90 ± 9.70, whereas in the control group, it was 39.26 ± 9.66 years. About 68% of our individuals were female in the study as well as control groups. Nearly 58% of the individuals in both study and control groups were from rural backgrounds. About 70% of the patients in the study sample were homemakers, whereas 66% of the controls were homemakers. The mean HAM-D score in the study group was 20.66 ± 2.57, while it was 3.46 ± 2.14 in the control group. HAM-D rating of depression in the study population was moderate depression, severe depression, and very severe depression in 32%, 42%, and 26%, respectively. The mean BMI in the study group was 22.45 ± 1.67, whereas it was 22.64 ± 1.60 in the control group. The sociodemographic and other variables are shown in [Table 1].
The mean TC in the study group was 172.06 ± 23.85 mg/dl in comparison to 197.80 ± 23.01 mg/dl in the control group. In the study group, the mean LDL-C was 91.56 ± 21.26 mg/dl, while it was 145.90 ± 39.24 mg/dl in the control group. The mean TG in the study group was 143.88 ± 84.63 mg/dl, and in the control group, it was 145.10 ± 83.84 mg/dl. The mean HDL-C in the study group was 38.7 ± 3.25 mg/dl, while it was 38.84 ± 3.58 mg/dl in the control group. There were significantly low levels of mean TC and mean LDL-C in the study group in comparison to the control group. No significant difference in the mean TG and mean HDL-C levels was found in between the two groups. The serum lipid parameters of cases and controls are shown in [Table 2].
|Table 2: Comparison of serum lipid parameters in the study and control groups|
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When correlated with severity of depression (as measured by HAM-D), there was a significant negative correlation with TC (r = −0.710; P = 0.0001), LDL-C (r = −0.608; P = 0.0001), and TG (r = −0.289; P = 0.042), whereas there was a nonsignificant negative correlation with HDL-C (r = −0.204; P = 0.155).
| Discussion|| |
In our study, significantly low levels of TC and LDL-C were found in the study group in comparison to the control group. Recent studies from India, on patients with endogenous depression, also found significantly low serum TC and LDL in depression patients in comparison to controls., Some of the previous studies have also found similar results with low serum TC and LDL-C in MDD patients., The relationship between serum TC and mood disorders is complex. Brain functioning and neurotransmission are dependent on cholesterol as it is important for the synthesis of neuroactive steroids which modulate different brain processes. Although only 2% of the body's weight is constituted by the brain, it contains almost 25% of the body's cholesterol. It has been suggested that a decrease in cell membrane cholesterol occurs in persons with a lower serum TC concentration. Extracellular concentration of serotonin in the brain is controlled by serotonin reuptake transporter (SERT), and it has been shown that membrane cholesterol modulates the activity of SERT. Thus, a plausible link is provided between an altered brain uptake of serotonin and depression in patients with lower serum TC. A study on fish testified the evolutionary origin of this low cholesterol-serotonin hypothesis in which the fishes were chronically administered cholesterol-lowering statin drugs. This study confirmed that statin-treated fish exhibited reduced plasma cholesterol, reduced indexes of telencephalic 5-hydroxyindoleacetic acid/serotonin, and increased aggressive behavior when compared to fish not on a statin drug. Studies have found that antidepressant treatment modulates these dyslipidemia patterns in depressed patients. A recent study on the effect of electroconvulsive therapy (ECT) on lipid parameters in depression found that the effective treatment of MDD with ECT led to a noticeable effect on serum lipid parameters. Whether these changes in lipid parameters are the effects of antidepressants and ECT or these are because of amelioration of depressive symptoms with successful treatment is not clear. Aksay et al. in their study summarized that these changes in lipid parameters by effective nonpharmacological treatment of depression by ECT are most likely specific to the antidepressant effect of ECT. A study by Eker et al. on metabolic effects of treatment of MDD with antidepressant found a distinct effect of antidepressant treatment on serum lipids, but they suggested that with the improvement of MDD, there might have been positive lifestyle changes like regular physical activity and feeding, which can explain the positive metabolic changes in patients with MDD, independent of antidepressant drug use.
In our study, no significant difference was there in HDL-C and TG between the two groups. Patra et al. in their study support our results and did not found any significant differences in serum TG and HDL between cases and control. However, Kale et al.'s study differs from our study and found both of these parameters significantly low in depressed patients as compared to controls. Further, there have been controversial findings in the literature about different lipid parameters in patients with depression. For example, in three recently published studies, there were higher TG, TC, and LDL-C levels and lower HDL-C levels in patients with MDD in comparison to healthy controls.,, Another recent study found higher TG and higher HDL-C levels in individuals with depressive disorders. Similarly, in a recent systematic review and meta-analysis on LDL-C levels in patients with depression, the studies in which LDL-C was taken as a continuous variable found a link between depression and low serum LDL-C, which was in contrast to the studies in which LDL-C was taken as a categorical variable. The contradictory results in the literature about lipid parameters in depression can be explained by a variety of factors like a wide range of differences in research designs and variations in methodology, which may include restrictions in age range, small size of sample, and heterogeneity in the study subjects., Other factors including measurement of serum cortisol, factors related to lifestyle like dietary habits, alcohol consumption, or smoking could explain these inconsistent findings in the literature.
In our study, TC, LDL-C, and TG had a significant negative correlation with the severity of depression as measured on HAM-D, whereas HDL-C had a nonsignificant negative correlation. Kale et al. in a recent study from India support our results. Another previous study also found a significant negative correlation between TC and severity of depression, but the correlation was not as strong as in our study.(r = 0.27; P < 0.05). However, like the lipid parameters, controversial studies with regard to the correlation between these lipid parameters and severity of depression are not uncommon in the literature. Enko et al. found a significant positive correlation between the severity of depression and TG (P = 0.027), TC (P = 0.048), and LDL-C (P = 0.018) concentrations and a nonsignificant negative correlation with HDL-C levels (P = 0.091). A previous Finnish longitudinal study on TG, LDL-C, and HDL-C levels during childhood and early adulthood, although indicated a rapid increase in TG to be predictive of depression onset, failed to show any association between LDL-C or HDL-C pattern change and symptoms of depression. A study from the recent past on associations between serum lipids parameters and MDD found an association between the severity of MDD and lipids/lipoproteins attenuated after adjustment for covariates, especially BMI.
Our results should be read with the following limitations. This was a cross-sectional study with cases and controls from two different groups, and changes in lipid parameters were not assessed longitudinally in the study group. Lifestyle-related factors such as alcohol use or smoking behavior, dietary habits, investigations to rule out medical illness, and family history of illness having effect on lipid profiles were not taken into account, and all of these factors could confound our result. Hence, the generalizability of our results is limited.
| Conclusions|| |
Drug-naïve individuals with MDD had significantly low TC and LDL-C in comparison to healthy individuals. A significantly negative correlation was there between the severity of MDD and TC, LDL-C, and TG. However, as discussed above, there are wide variations in the existing literature. To arrive at a common agreement and to fully elucidate the associations between MDD and blood lipid parameters, we suggest to conduct prospective studies and measurements of serum lipid parameters on follow-up while taking into account different variables affecting blood lipid levels.
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Conflicts of interest
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| References|| |
Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: A quantitative review of primary prevention trials. BMJ 1990;301:309-14.
Capuzzi E, Bartoli F, Crocamo C, Malerba MR, Clerici M, Carrà G. Recent suicide attempts and serum lipid profile in subjects with mental disorders: A cross-sectional study. Psychiatry Res 2018;270:611-5.
Aksay SS, Bumb JM, Janke C, Biemann R, Borucki K, Lederbogen F, et al
. Serum lipid profile changes after successful treatment with electroconvulsive therapy in major depression: A prospective pilot trial. J Affect Disord 2016;189:85-8.
Tedders SH, Fokong KD, McKenzie LE, Wesley C, Yu L, Zhang J. Low cholesterol is associated with depression among US household population. J Affect Disord 2011;135:115-21.
Ong KL, Morris MJ, McClelland RL, Maniam J, Allison MA, Rye KA. Lipids, lipoprotein distribution and depressive symptoms: The multi-ethnic study of atherosclerosis. Transl Psychiatry 2016;6:e962.
Moreira FP, Jansen K, Cardoso TA, Mondin TC, Magalhães PV, Kapczinski F, et al
. Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode. J Psychiatr Res 2017;92:119-23.
Nakao M, Yano E. Relationship between major depression and high serum cholesterol in Japanese men. Tohoku J Exp Med 2004;204:273-87.
van Reedt Dortland AK, Giltay EJ, van Veen T, van Pelt J, Zitman FG, Penninx BW. Associations between serum lipids and major depressive disorder: Results from the Netherlands study of depression and anxiety (NESDA). J Clin Psychiatry 2010;71:729-36.
Olusi SO, Fido AA. Serum lipid concentrations in patients with major depressive disorder. Biol Psychiatry 1996;40:1128-31.
Maes M, Smith R, Christophe A, Vandoolaeghe E, Van Gastel A, Neels H, et al
. Lower serum high-density lipoprotein cholesterol (HDL-C) in major depression and in depressed men with serious suicidal attempts: Relationship with immune-inflammatory markers. Acta Psychiatr Scand 1997;95:212-21.
Hummel J, Westphal S, Weber-Hamann B, Gilles M, Lederbogen F, Angermeier T, et al
. Serum lipoproteins improve after successful pharmacologic antidepressant treatment: A randomized open-label prospective trial. J Clin Psychiatry 2011;72:885-91.
World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. Geneva: World Health Organization; 1993.
Gautam S, Nijhawan M, Kamal P. Standardisation of Hindi version of Goldbergs general health questionnaire. Indian J Psychiatry 1987;29:63-6.
] [Full text]
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.
Kale AB, Kale SB, Chalak SS, Tankhiwale S, Bang G, Agrawal M, et al
. Lipid parameters – Significance in patients with endogenous depression. J Clin Diagn Res 2014;8:17-9
Patra BN, Khandelwal SK, Chadda RK, Ramakrishnan L. A controlled study of serum lipid profiles in Indian patients with depressive episode. Indian J Psychol Med 2014;36:129-33.
] [Full text]
Rabe-Jabłońska J, Poprawska I. Levels of serum total cholesterol and LDL-cholesterol in patients with major depression in acute period and remission. Med Sci Monit 2000;6:539-47.
Tuem KB, Atey TM. Neuroactive steroids: Receptor interactions and responses. Front Neurol 2017;8:442.
Björkhem I. Crossing the barrier: Oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 2006;260:493-508.
Engelberg H. Low serum cholesterol and suicide. Lancet 1992;339:727-9.
Scanlon SM, Williams DC, Schloss P. Membrane cholesterol modulates serotonin transporter activity. Biochemistry 2001;40:10507-13.
Owens MJ, Nemeroff CB. Role of serotonin in the pathophysiology of depression: Focus on the serotonin transporter. Clin Chem 1994;40:288-95.
Aguiar A, Giaquinto PC. Low cholesterol is not always good: Low cholesterol levels are associated with decreased serotonin and increased aggression in fish. Biol Open 2018;7. pii: bio030981.
Eker ÖO, Özsoy S, Baki EK, Dogan H. Metabolic effects of antidepressant treatment. Arch Neuropsychiatry 2017;54:49.
Enko D, Brandmayr W, Halwachs-Baumann G, Schnedl WJ, Meinitzer A, Kriegshäuser G. Prospective plasma lipid profiling in individuals with and without depression. Lipids Health Dis 2018;17:149.
Nunes SO, Piccoli de Melo LG, Pizzo de Castro MR, Barbosa DS, Vargas HO, Berk M, et al
. Atherogenic index of plasma and atherogenic coefficient are increased in major depression and bipolar disorder, especially when comorbid with tobacco use disorder. J Affect Disord 2015;172:55-62.
Oh J, Kim TS. Serum lipid levels in depression and suicidality: The Korea national health and nutrition examination survey (KNHANES) 2014. J Affect Disord 2017;213:51-8.
Persons JE, Fiedorowicz JG. Depression and serum low-density lipoprotein: A systematic review and meta-analysis. J Affect Disord 2016;206:55-67.
Beydoun MA, Beydoun HA, Dore GA, Fanelli-Kuczmarski MT, Evans MK, Zonderman AB. Total serum cholesterol, atherogenic indices and their longitudinal association with depressive symptoms among US adults. Transl Psychiatry 2015;5:e518.
Elovainio M, Pulkki-Råback L, Kivimäki M, Jokela M, Viikari J, Raitakari OT, et al
. Lipid trajectories as predictors of depressive symptoms: The Young Finns Study. Health Psychol 2010;29:237-45.
[Table 1], [Table 2]