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ORIGINAL ARTICLE |
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| Relationship between lipid profile and suicide attempts in first-episode major depressive disorder patients |
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Srikrishna Nukala1, Archana Vinnakota2, Srinivas Singisetti3, Shvetha Chilukuri4, Niveditha Vasireddy3, Venkata Abhilash Garapati4, Vidya Sanapala4, Ramya Spandana Tata5, Yoshita Rao Aneepu6
1 Professor, Department of Psychiatry, GITAM Institute of Medical Sciences and Research, Visakhapatnam, Andhra Pradesh, India
2 Associate Professor, Department of Psychiatry, GSL Medical College, Rajahmundry, Andhra Pradesh, India
3 Associate Professor, Department of Psychiatry, GITAM Institute of Medical Sciences and Research, Visakhapatnam, Andhra Pradesh, India
4 Assistant Professor, Department of Psychiatry, GITAM Institute of Medical Sciences and Research, Visakhapatnam, Andhra Pradesh, India
5 Senior Resident, Department of Psychiatry, GITAM Institute of Medical Sciences and Research, Visakhapatnam, Andhra Pradesh, India
6 MBBS, Rangaraya Medical College, Kakinada, Andhra Pradesh, India
Click here for correspondence address and email
| Date of Submission | 29-Oct-2022 |
| Date of Acceptance | 23-Jan-2023 |
| Date of Web Publication | 28-Feb-2023 |
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Introduction: Cholesterol is considered a core component of the central nervous system, essential for cell membrane stability and the correct functioning of neurotransmitters. Cholesterol plays a vital role in the brain's second messenger system related to the mechanism of action of antidepressant drugs and mood stabilizers. It may be involved in the etiology and pathogenesis of mood disorders.
Aim: This study aims to explicate facts and views about the role of cholesterol levels in depressive disorder and suicidality.
Materials and Methods: This was a cross-sectional comparative study where the patients were divided into two groups, i.e., subjects with first-episode major depressive disorder (MDD) with a recent suicide attempt and without suicide attempt. A detailed psychiatric interview, their sociodemographic characteristics, and clinical details were noted on a structured pro forma. MDD diagnosis in the patients was made using the Diagnostic and Statistical Manual of Mental Disorders V. Hamilton Depression Rating Scale was used on subjects to determine the patient's level of depression. After the overnight fast, blood samples are collected between 6 am and 7 am. Total cholesterol (TC), triglyceride, high-density lipid levels, and low-density lipid levels were measured on the Cobas c311 machine.
Results: In the current study, a positive correlation was noted in TC (r = 0.488) and low-density lipid (LDL) levels (r = 0.549) in subjects with depression and suicide attempts.
Conclusion: The present study results add to the other studies that support an association between serum cholesterol with depression and suicide. Understanding the significance of lower cholesterol levels is central for future treatments of depressive disorder.
Keywords: Depression, fatty acids, serum cholesterol, suicide
How to cite this URL:
Nukala S, Vinnakota A, Singisetti S, Chilukuri S, Vasireddy N, Garapati VA, Sanapala V, Tata RS, Aneepu YR. Relationship between lipid profile and suicide attempts in first-episode major depressive disorder patients. Arch Ment Health [Epub ahead of print] [cited 2023 Mar 24]. Available from: https://www.amhonline.org/preprintarticle.asp?id=370761 |
| Introduction | |  |
The World Health Organization reports that 7.5% of India's 135-crore population is suffering from some kind of mental health problem, major or minor. The highest rates of suicide in India are between the ages of 15 and 29. Shockingly, every 3 s, there is one suicide attempt in the country.[1] Over and above that, 90% of people who die by suicide suffer from one or more psychiatric disorders, especially major depressive disorder (MDD), which accounts for 59%–87% of all suicides.[2],[3] Literature suggests that factors such as gender, family history of mental illness, depression, and comorbidities contribute to the risk of suicide.[4] In recent decades, many investigators have been trying to find possible biomarkers for taking one's life. The role of cholesterol in depressive disorders and suicide has always been the focus of psychiatric research.[5],[6]
Cholesterol is considered a core component of the central nervous system (CNS), essential for cell membrane stability, and the correct functioning of neurotransmitters.[7] Cholesterol plays a vital role in the brain's second messenger system related to the mechanism of action of antidepressant drugs and mood stabilizers. It may be involved in the etiology and pathogenesis of mood disorders.[8],[9] Many studies have shown that patients with MDD have lower total cholesterol (TC) levels than nondepressed individuals.[10],[11] Furthermore, low high-density lipoprotein (HDL-C) cholesterol concentration and high ratios of TC/high-density lipoprotein (TC/HDL-C) and HDL = high- density lipoprotein, LDL= low -density lipoprotein are noted in patients suffering with MDD.[12],[13] It has been observed that serum cholesterol is considerably associated with suicidal behaviors.[14],[15] Moreover, it is found that adiposity and a high waist-to-hip ratio may be related to an increased risk of suicide.[16]
All considered possible usefulness in evaluating serum cholesterol levels in affective patients may be the prediction of the development of suicidal ideation.[5] However, during the last 2 years, the involvement of serum cholesterol in the pathogenesis of MDD has been questioned based on some recent studies that have not found any correlation between serum cholesterol and depressive symptoms.[17]
Therefore, the present study aims to explicate facts and views about the role of cholesterol levels in depressive disorder and suicidality.
| Materials and Methods | | |
This cross-sectional comparative study started on January 2022 and was carried out until the patient-required numbers were obtained, until August 2022. After getting the necessary permission from the ethics committee, using purposive and convenient sampling, those subjects who were satisfied with inclusion and exclusion criteria were taken as sample size. Subjects were recruited from those visiting department of psychiatry at a tertiary care hospital in Northern Andhra Pradesh, India.
The study subjects were divided into two groups – subjects with a first episode of MDD with a recent suicide attempt and without a suicide attempt. Subjects who are 18 years old or more capable of reading and communicating in the English language and who did not receive any drugs, including antidepressants, anti-anxiety drugs, antipsychotics, and other drugs that affect lipid levels, and having body mass index within normal range and willing to give consent were included in the study. Subjects with alcohol, nicotine use, or other drug abuse issues, pregnancy or lactation, and suffering from any other medical illness were excluded from the study.
During the study period, sixty patients, i.e., 30 from each group who met the inclusion criteria, were subjected to a detailed psychiatric interview, their sociodemographic characteristics and clinical details were noted on a structured pro forma, and MDD diagnosis in the patients was made using the Diagnostic and Statistical Manual of Mental Disorders V.[18] The Hamilton Depression Rating Scale (HAM-D) was used on subjects to determine the patient's level of depression.[19] Although the HAM-D scale consists of 21 items, the scoring is based on the first 17. It generally takes 15–20 min to complete the scale and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe, and nine items are scored from 0 to 2.
Blood sample
After overnight fast, blood samples were collected between 6 am and 7 am. All samples were sent to the laboratory center of the hospital immediately, and measurements were taken before 11 am in the morning of the same day. The TC, total triglyceride (TG), high-density lipid levels (HDL), and low-density lipid (LDL) levels were measured on the Cobas c311 machine. For TC levels, the method used was cholesterol oxidase-peroxidase, and for LDL, TG, and HDL, direct method (enzymatic–colorimetric) was used.
| Results | | |
All statistical analysis was done by using IBM SPSS statistics (Version 16), Chicago, United States ans MS Excel 2007. Qualitative variables were expressed as frequencies and percentages. Quantitative variables were expressed as means and standard deviations. The unpaired student test was used for two-group means comparison. ANOVA was used for more than two-group means comparison. Karl Pearson's correlation coefficient was used to explore the relationship between two variables. For all statistical analyses, P < 0.05 is considered statistically significant.
[Table 1] depicts the demographic characteristics of the study subjects. Majority of patients in the depression with suicide attempt group were females (60%) and married (43.3%). The nature of suicide attempt was planned in 60% of the study population and poisoning (53.4%) was the most common mode of suicide attempt.
[Table 2] depicts that majority of the patients in both the groups were found have very severe HAM-D scores (73% in depression with suicide attempt and 43.3% in depression without suicide attempt).
[Table 3] shows that there was a mean significant difference in TC (P=0.015<0.05), LDL (P=0.000<0.01), and TG (P=0.000<0.01) between depression with suicide attempt and depression without suicide attempt.
[Table 4] depicts that HAM-D score was significantly positively correlated with TC (r = 0.488, P = 0.006 < 0.01) and LDL (r = 0.549, P = 0.002 < 0.01) and inversely correlated with HDL (r =−0.420, P = 0.021 < 0.05) in suicide attempt group, and no significant correlations exist with no suicide attempt group. | Table 4: Correlation between Hamilton Depression Rating Scale and lipid profile
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[Figure 1] depicts that there was a positive correlation between HAM-D score and TC in depression with suicide attempt group. | Figure 1: Correlation between HAM-D and TC. HAM-D: Hamilton Depression Rating Scale, TC: Total cholesterol
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[Figure 2] depicts a positive correlation between HAM-D score and LDL in the depression with suicide attempt group. | Figure 2: Correlation between HAM-D and LDL cholesterol. HAM-D: Hamilton Depression Rating Scale, LDL: Low-density lipoprotein
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[Figure 3] depicts an inverse correlation between HAM-D score and HDL in the depression with suicide attempt group. | Figure 3: Correlation between HAM-D and HDL. HAM-D: Hamilton Depression Rating Scale, HDL: High-density lipoprotein
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[Table 5] depicts a significant mean difference in LDL (P=0.042<0.05) with the duration of illness in the suicide attempt group. And there was a significant mean difference in TC (P=0.044<0.05) in relation to the duration of illness in the no-suicide attempt group. [Table 6] depicts that there was a significant mean difference in LDL (P=0.044<0.05) and HDL (P=0.040<0.05) with age among depression with the suicide attempt group. The present study results did not show any significant association of lipid profile with marital status and gender among the two groups. | Table 5: Association between lipid profile and duration of illness among two groups
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| Discussion | | |
In 1992 Engelberg presented a hypothesis linking cholesterol and the serotonergic system.[20] He hypothesized that low serum cholesterol levels might be accompanied by changes in the density and function of serotonergic receptors and transporters, as well as serotonin precursors that may cause an increase in suicide ideation. Maes et al., studied the haptoglobin phenotype connected with chromosome 16, where the gene encoding lecithin-cholesterol acetyltransferase (LCAT) (enzyme catalyzing cholesterol esterification in the blood) is located.[21] The authors hypothesized that a low concentration of esterified cholesterol could be linked to the defect in chromosome 16, which may increase one's susceptibility to depressive disorder. Considering a possible hypothesis between lipid levels with depression and suicide attempts, we discuss findings from the current study with these.
Serum cholesterol in relationship to suicidal behavior, depressive disorder, and demographic characteristics
With regard to demographic parameters taken into consideration in the current study, the results showed that the risk of a suicide attempt is higher in females [Table 1]. Onuegbu et al.'s study also had similar findings.[22] Sixty percent of the attempts were planned in nature. The most typical method was poisoning with organophosphorus agents or drug overdose, which probably reflects the easy availability of these substances at home and in local markets.
The current study did not find any association between gender and cholesterol levels. However, it has been noted in some studies that the male gender is associated with lower cholesterol levels in various psychiatric disorders.[23] With relation to the duration of illness, depressive disorder patients with suicide attempts have statistically significant higher mean values of LDL with illness (P < 0.05) [Table 5].
In depressive disorder patients with suicide attempts, HAM-D score was found to have a positive correlation with TC and LDL values, depicting that TC and LDL cholesterol levels were found to be increasing with the severity of depression. HAM-D scores were negatively correlated (r= -0.420)with HDL, indicating that low levels of HDL cholesterol correlate with increasing severity of depression [Table 4] and [Figure 1], [Figure 2], [Figure 3].
In the present study, serum cholesterol levels in patients with depressive disorder with suicide attempts were found to have significantly lower mean values of TC and LDL and higher TG levels than those of depressive disorder patients without suicide attempts [Table 3]. On seeing an association between age and lipid profile, low LDL levels and high HDL levels were noted in the 18–30-year age group among depression with suicide attempt group [Table 6].
Low cholesterol levels could cause functional consequences in the lipid raft that are made up of microstructures such as cholesterol, sphingolipids, saturated fatty acids, and gangliosides. These uneven lipid rafts react with other cytokines promoting a process of inflammation through n-3 and Toll-like receptors. When Cholesterol levels decrease, the ratio PUFA N-6:N-3 becomes unbalanced and N-6 increases, leading to production of pro-inflammatory cytokines, namely interleukin 6, increasing the inflammatory process.[24] Many of these pro-inflammatory molecules cross the blood–brain barrier causing psychiatric symptoms and mood disorders.[25] The second theory is about the serotoninergic system. A reduction of cholesterol in the lipid rafts produces a decrease in the viscosity of the neuronal membranes. Low density leads to a failure in the synaptic transmission, causing a reduction in serotonin intake via serotonin receptors (5-HT1A). Additionally, fatty acid deficiency promotes impaired serotonin and dopamine neurotransmission in the frontal cortex.[25]
To summarize, low levels of cholesterol and fatty acids affect the formation of lipid rafts leading to a decrease in serotonin transmission and neuroinflammation in the nervous system, thereby leading to psychiatric disorders, particularly mood disorders.
Studies that had an association between suicide and serum cholesterol
Gallerani et al. published data from a controlled population of 331 parasuicides and found a lower cholesterol level in the suicide group.[26] Sullivan et al. investigated the association between TC and suicidality in a sample of 90 men and women with MDD and found a significant association between lower cholesterol levels and suicide.[27] Kunugi et al. similarly found a relationship between low serum cholesterol and suicide attempts.[28] Papassotiropoulos et al. reported that the risk of acute suicidality decreased with increasing TC levels regardless of age, gender, and nutritional status.[29]
Studies that did not show an association between suicide and serum cholesterol
Huang, who estimated serum lipid profiles, over 2 years, in 168 subjects (109 patients with depression and 59 healthy controls), observed no significant differences in serum lipid profiles between MDD patients with or without suicide attempts.[30] de Leon et al. evaluated 193 current suicide attempters and found no association between cholesterol levels and suicide risk.[31] D'Ambrosio et al.'s study also did not find any association between serum lipid levels and suicide in bipolar disorder patients.[32]
| Conclusion | | |
The current study results add to the other studies that support the association between serum cholesterol with depression and suicide. There is much ongoing research on omega-3 fatty acids in various psychiatric disorders, particularly mood disorders, but serum cholesterol is often overlooked. Wherein reality, these two are closely linked to depressive disorder. Understanding the significance of low cholesterol levels is vital for future treatments for depressive disorder.
Future directions
Considering serum cholesterol's role in the pathogenesis of MDD, we would like to recommend more longitudinal studies on serum cholesterol, depression, and suicide, as there are minimal biomarkers in various psychiatric disorders. In addition, research on how serum cholesterol affects CNS cholesterol metabolism should be conducted to fully establish the role of cholesterol in depression and suicidal behaviors, and studies assessing genes in the synthesis of cholesterol pathways in various mental illnesses are recommended.
Limitations
Some limitations need to be considered in the current study, including the small sample size of the group studied.The abscence of a healthy control group would also limit the conclusions drawn from the subjects in the depressed population.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Archana Vinnakota,
Department of Psychiatry, GSL Medical College, Rajahmundry - 533 296, Andhra Pradesh
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/amh.amh_170_22
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6] |
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