ORIGINAL RESEARCH
Association of Depression With Selenium Deficiency and Nutritional Markers in the Patients with End-Stage Renal Disease on Hemodialysis Maryam Ekramzadeh, PhD,* Zohreh Mazloom, PhD,* and Mohammadmahdi Sagheb, MD† Objective: Depression is considered as the most common psychological problem in hemodialysis (HD) patients. As there is little evidence regarding the association of depression with serum selenium level as an antioxidant in these patients, the current survey investigates the possible relationship between depression and nutritional status including serum selenium levels. Design: Cross-sectional study. Setting and Subjects: A total of 110 HD patients and 40 healthy controls were enrolled in the study. The patients were in the age range of 18 to 85 years, who had been on hemodialysis for at least 3 months without any acute illness. Main Outcome Measure: Beck Depression Inventory was used for assessing the severity of depression. Malnutrition was evaluated through subjective global assessment (SGA) and malnutrition inflammation score (MIS). Serum selenium levels and routine laboratory markers were measured from fasting samples. Results: Sixty-two percent of the patients had some degree of depression based on Beck Depression Inventory score. HD patients were considered to be selenium deficient after comparing the mean value of serum selenium between the patients and controls (P , .001). No significant difference was found in serum selenium levels between depressed HD patients and the rest of patients without depression. The mean level of SGA and MIS in the depressed patients was significantly higher than the rest of patients (P 5 .03 and P 5 .04, respectively). Also lower levels of hemoglobin and serum albumin were significantly seen in depressed patients compared with nondepressed ones (P 5 .004 and P 5 .04, respectively). Conclusions: Although the HD patients in this study were selenium deficient, no significant association was found between depression and selenium. In addition, depression was more prevalent in malnourished HD patients with higher SGA and MIS scores and lower serum albumin and hemoglobin levels. Ó 2015 by the National Kidney Foundation, Inc. All rights reserved.
Introduction
D
EPRESSION IS THE most common psychological problem in the end-stage renal disease (ESRD) patients undergoing hemodialysis (HD).1,2 HD affects the life of patients in different aspects of social, physical, occupational, and personal. Thus, depression may be a normal response to these situations in HD patients.3 A mutual link has been found between depression and chronic disease state in the way that depression could have a great impact on nutrition, appetite, and immune system.1,4 It has been demonstrated that depression is an important predictor of morbidity,5 mortality,6-10 and lower quality of life11 in patients undergoing HD. Depression as an inflammatory disease characterized by accumula* Department of Clinical Nutrition, Shiraz School of Nutrition & Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. † Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Financial Disclosure: See Acknowledgments on page XXX. Address correspondence to Zohreh Mazloom, PhD, Department of Clinical Nutrition, Shiraz School of Nutrition & Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. E-mail: [email protected] Ó 2015 by the National Kidney Foundation, Inc. All rights reserved. 1051-2276/$36.00 http://dx.doi.org/10.1053/j.jrn.2014.12.005
Journal of Renal Nutrition, Vol -, No - (-), 2015: pp 1-7
tion of highly reactive oxygen species12,13 is associated with an increased risk of cardiovascular disease and atherosclerosis.14 Selenium as an essential antioxidant has a modulatory role in brain function and mood stabilization through attenuation of inflammation.12,13,15,16 Previous studies have demonstrated that serum levels of selenium are decreased in HD patients because of insufficient dietary intake or losses through HD membranes.17 Depression is also linked with malnutrition in the way that it is more severe in depressed dialysis patients.18 Despite the high prevalence and importance of depression in HD population, many patients often go unnoticed by the health care professionals.3 The Beck’s Depression Inventory (BDI) is a standard self-administered questionnaire for screening HD patients with depression.1,2 Although there is a large body of literature on depression in chronic kidney disease (CKD), no study evaluated the association of depression with selenium level, nutritional and biochemical markers in HD patients. In addition, a few studies examining the relationship between selenium and depression in healthy population12,15 have yielded inconsistent results, and none of these studies considered the association of selenium with depression in HD patients. The aim of this study was to elucidate the possible relationship between depression and serum 1
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selenium and nutritional and biochemical parameters in a group of patients undergoing HD.
Methods Patient Selection The present study included 110 patients with ESRD on HD from the outpatient clinics of our hospital. Forty healthy control subjects without any endocrine or metabolic disease were also recruited from hospital personnel with the aim of comparing depression score and serum selenium levels between healthy population and HD patients. The data were collected from August 1 to December1, 2013. All the participants gave their informed consent in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The patients were in the age range of 18 to 85 years, who had been on HD for at least 3 months without any acute illness. All enrolled patients were on HD 3 to 3 times a week for 3 hours using low flux dialysis filters with polysulfone/polyamide membranes and reverse osmosis purified water and bicarbonatecontaining dialysis solution. The subjects who took antidepressants, oral iron, vitamin B12, folate, and antioxidant supplements were excluded from the study. Clinical and Nutritional Assessment Demographic data (age, gender, level of education, marital status, employment, and duration of HD) were collected through questionnaires filled by the main investigator. The BDI scoring system1,2,19,20 was used to evaluate the severity of depression in HD patients. The BDI is a standard 21-question multiple choice questionnaire with a self-report inventory which measures the common clinical symptoms of depression like feelings of hopelessness, sadness, anhedonia, guilt, fatigue, and also changes in sleep, weight, appetite, and libido. The value of each component ranges from 0 to 3. At the end, the sum of scores was as follows: 0 to 9: no depression; 10 to 13: borderline; 14 to 19: mild depression; 20 to 28: moderate depression; and 29 to 63: severe depression. Higher scores were indicative of more severe depression. The questions were read and replied by each patient, and the total score was compared with a key to decide whether the patient was categorized as depressed or not. BDI questionnaire was filled for both groups of HD patients and healthy control subjects. Valid nutritional markers such as subjective global assessment (SGA) and malnutrition inflammation score (MIS) were checked in all patients through face-to-face interview. SGA questionnaire was a useful tool for evaluating nutritional status in HD patients. It includes questions on physical examination (muscle and subcutaneous fat wasting, edema), and nutritional history (weight change during the preceding 2 weeks and 6 months, appetite, food intake, and gastrointestinal symptoms). The overall status was interpreted based on the sum of scores as follows (the score for each item from 0 to 5): a score of less than 10 well-
nourished, 10 to 17 mildly to moderately malnourished, and higher than 17 severely malnourished.21 MIS scoring system is more quantitative and complete than SGA. It had all the similar parts explained earlier in SGA. It also included 2 nutritional laboratory markers (albumin and transferrin). Each item scores from 0 to 3. The sum of scores of all 10 components could be a good indicator of nutritional status. The higher the score was, the more severe the malnutrition and inflammation was.22 Serum selenium levels were measured in both groups of healthy controls and HD patients from fasting serum samples using graphite furnace atomic absorption spectrometry method.23 The blood samples were taken from the patient’s arm used for HD cannulae just before the beginning of the HD session. The serum in both groups of healthy and HD patients was obtained by centrifugation at 3000 g/minute for 5 minutes and stored at 270 C in the laboratory of the local hospital for further analysis. Other routine laboratory markers (as listed in Table 3) such as blood urea nitrogen, creatinine, albumin, hemoglobin (Hb), serum iron, ferritin, and lipid profile were assessed for each patient using standard automated techniques in facilities.
Selenium Measurement Settings The wavelength used was 196.0 nm with slit width 1.0 nm and lamp current: 10.0 mA. Calibration mode was standard additions. Adding inorganic selenium to sera before sample reduction yielded valid calibration slopes by standard additions. The final furnace conditions and temperature program for drying of serum for selenium detection are depicted in Table 1. Statistical Analysis Data were analyzed using SPSS 18 (SPSS Inc., Chicago, IL) statistical software package. All the data were assessed for normality of distribution, using the Kolmogorov–Smirnov test. Depression score in 2 groups of HD patients and healthy controls with regard to confounding factors (age, sex, marriage, job, education level) were compared using covariance analysis. To compare variables according to the Beck depression score among HD patients, Table 1. Standard Addition Steps in Measuring Serum Selenium Levels Gas Step Temp Flow Number Degree (C) Time (s) (L/min) 1 2 3 4 5 6 7 8 9
85 95 120 400 1,000 1,000 2,600 2,600 2,600
5.0 40.0 10.0 5.0 1.0 2.0 0.8 2.0 2.0
3.0 3.0 3.0 3.0 3.0 0.0 0.0 0.0 3.0
Gas Type Normal Normal Normal Normal Normal Normal Normal Normal Normal
Read Store No No No No No No Yes Yes No
No No No No No Yes Yes Yes Yes
ASSOCIATION OF DEPRESSION WITH SELENIUM AND NUTRITIONAL MARKERS
independent sample t test, Mann-Whitney U test, and c2 test were used. The correlations were first calculated by the Pearson correlation test and then the variables with significant coefficients were tested again in backward multivariate regression model. P values ,.05 were considered statistically significant.
Results A total of 110 HD patients and 40 healthy controls participated in this cross-sectional study. The demographic characteristics of healthy subjects could be seen in Table 2. The mean age of the HD patients was 47.81 6 14.80 years (mean 6 standard deviation). In our study, 38.9% of the patients were female and 70% were married. Seventy-two percent of them were unemployed, whereas 57.4% of the total patients had education of less than high school. The mean duration on HD and efficacy of dialysis (KT/V) were 34.5 6 3.81 months and 1.36 6 0.02 (mean 6 standard error) respectively. The 2 main causes of renal failure in this population were diabetes (38.9%) and hypertension (37%). Signs of depression were found in 62% of all the patients. Among them 28.7% had mild depression (BDI 5 14–19), 23.1% had moderate depression (BDI 5 20–28), and 10.2% had severe depression (BDI $ 29). The average BDI was 16.81 6 9.27 (range 0–56). Serum selenium levels and depression score based on BDI were compared between HD patients and healthy subjects. As shown in Table 2, serum selenium levels in HD patients were significantly lower than healthy controls (P , .001). Regarding depression, the mean BDI score in HD patients (16.99 6 9.21) was significantly higher than healthy individuals (11.46 6 8.87) (P 5.009) after adjusting for age (P 5.26), gender (P 5.42), marital status (P 5.19), employment (P 5 .09), and education level (P 5 .86) as confounding factors using analysis of covariance. The HD patients were divided into 2 groups based on Beck depression score: those with normal BDI score (nondepressed patients, group 1: BDI ,10, n 5 30) and those with some degrees of depression (borderline to severe) (HD patients with clinical depression, group 2: BDI $ 10, n 5 80). Higher BDI scores in group 2 were indicTable 2. Selenium Levels and Beck Depression Scores of Hemodialysis Patients and Controls Variable
Hemodialysis (n 5 110)
Controls (n 5 40)
P Value
Selenium (mg/L) 94.78 6 10.80 111.007 6 15.93 ,.001* Beck depression 16.99 6 9.21 11.46 6 8.87 .009† score Age (y) 47.81 6 14.80 45.65 6 9.87 .09‡ Female (%) 38.9 50 .22‡ The data are shown as mean 6 standard deviation. *P , .05 by t test. †P , .05 by analysis of covariance. ‡Other 2 insignificant P values by t test.
3
ative of more severe depressive symptoms, whereas the patients in group 1 had no clinical depression. Selenium levels, nutritional markers, and other biochemical factors were compared between the 2 groups. The results have been shown in Table 3. The HD patients with depression in group 2 had significantly higher SGA (P 5 .03) and MIS (P 5 .04) scores. In addition, levels of Hb (P 5 .004) and serum albumin (P 5 .04) were significantly lower in depressed HD patients in group 2. Also rate of employment was significantly lower in HD patients with higher BDI scores (P 5 .03). But no significant difference was found regarding serum selenium levels between 2 groups. As seen in Table 3, other demographic characteristics and biochemical parameters were not significantly different when comparing the 2 groups. The correlations between Beck depression score and measured variables are shown in Table 4. The variables with significant coefficient were age (r 5 20.21, P 5 .02), SGA (r 5 0.32, P 5 .001), MIS (r 5 0.32, P 5 .001), Hb (r 5 20.26, P 5 .007), and albumin (r 5 20.27, P 5 .004). After analyzing these significant variables in regression models, results showed no correlation between BDI score and clinical variables except for age (P 5 .03), SGA (P , .001), and Hb (P 5 .02) (Table 5).
Discussion The results of this study revealed new findings in HD patients regarding the association of selenium status with depression. Our results did not reveal an association between selenium level as a potential novel modifiable factor in the primary prevention of depression and BDI score but rather tested whether there was an association. Although the patients in this study were selenium deficient compared with healthy controls, we found no difference in serum selenium concentration between the HD patients with depression and the normal ones without depression based on Beck depression score. In addition, similar to the results of previous studies18,24 we found that depressed HD patients with greater BDI scores had more severe malnutrition based on SGA, MIS, serum albumin, and Hb levels meaning that HD patients with depression were more malnourished and anemic compared with the ones without depression. Clinical depression is emerging as the most common and significant psychological problem in patients with ESRD undergoing HD.1,2,25 HD patients with clinically significant depression have lower quality of life and higher rates of morbidity and mortality.5,9-11 Depression in HD patients is also related to increased perception of pain which in turn may lead to more discomfort and mortality rate. On the other hand, chronic pain which is a prevalent characteristic in HD patients is associated with increased depression and lower quality of life by altering brain chemistry.26,27As BDI scores of $11 have a sensitivity and specificity of about 90%, this questionnaire
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Table 3. Clinical and Nutritional Parameters in Hemodialysis Patients Based on Beck Depression Scores Parameter Age (y) Duration of dialysis (mo) Gender (female %) Education level of less than high school (%) Rate of marriage (%) Rate of employment (%) Selenium (mg/L) SGA MIS Albumin (g/dL) Hb (g/dL) BMI (kg/m2) Weight (kg) BUN (mg/dL) Creatinine (mg/dL) Kt/V Uric acid (mg/dL) Total protein (g/dL) Calcium (mg/dL) Phosphorus (mg/dL) PTH (pg/dL) Potassium (mg/dL) Sodium (mEq/L) FBS (mg/dL) TG (mg/dL) Total cholesterol (mg/dL) HDL (mg/dL) LDL (mg/dL) AST (IU/L) ALT (IU/L) Alkaline phosphatase (IU/L) Ferritin (ng/mL) Total iron binding capacity (mg/dL) Iron (mcg/dL)
Group 1 (BDI , 10, n 5 30)
Group 2 (BDI $ 10, n 5 80)
52.38 6 2.6 31.44 6 6.13 30.8 46.2
46.41 6 1.69 35.46 6 4.84 40.7 60
81.5 44.4 94.23 6 2.33 11.61 6 0.63 6.52 6 0.68 4.52 6 0.08 13.80 6 0.46 23.93 6 1.15 69.46 6 2.96 48.82 6 3.28 7.07 6 0.45 1.35 6 0.02 5.03 6 0.2 7.11 6 0.2 8.96 6 0.15 5.3 6 0.22 311.97 6 73.71 5.40 6 0.15 139.82 6 0.67 116.47 6 12.66 153.39 6 10.6 168.60 6 7.10 36 6 1.49 104.56 6 6.89 16.69 6 1.47 17.60 6 1.92 282.56 6 28.3 533.16 6 113.42 268.95 6 14.88 82.17 6 8.50
66.7 23.5 94.33 6 1.10 13.36 6 0.41 8.28 6 0.43 4.27 6 0.06 12.25 6 0.25 24.03 6 0.58 65.73 6 1.62 46.65 6 1.94 8.18 6 1.28 1.42 6 0.05 4.73 6 0.11 7.14 6 0.09 8.97 6 0.07 5.12 6 0.15 374.05 6 35.99 5.36 6 0.08 139.87 6 0.35 119.40 6 9.15 169.44 6 10.61 169.15 6 5.01 35.85 6 1.20 95.87 6 4.29 14.02 6 0.86 14.33 6 1.13 417.77 6 48.22 599.16 6 57.30 267.76 6 7.38 73.05 6 3.65
P Value .07 .66 .36 .5 .14 .03 .96 .03* .04* .04* .004* .93 .26 .58 .64 .46 .22 .9 .99 .55 .42 .79 .95 .87 .42 .95 .95 .31 .13 .15 .13 .58 .94 .26
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BDI, Beck Depression Inventory; BMI, body mass index; BUN, blood urea nitrogen; FBS, fasting blood sugar; Hb Hemoglobin; HDL, high-density lipoprotein; LDL low-density lipoprotein; MIS, malnutrition inflammation score; PTH (Parathyroid Hormone); SGA, subjective global assessment; TG, triglyceride. The data are expressed as mean 6 mean standard error. *P values are statistically significant.
is used as a valid screening tool for diagnosing depression in patients with CKD.28 The prevalence of depression in our patients was 62%. This high rate was somehow similar to the reports of the study done by Roozbeh et al1 in which 76% of the HD patients had some degree of depression based on BDI score. In other studies, the prevalence of depression was lower than ours. In the work done by Ossareh et al29, depression was documented in 40.7% of 150 maintenance HD patients according to BDI. In the study by Stasiak et al30, depression was found in 22.6% of 128 HD patients based on BDI. The results of another study showed that depression signs of BDI were found in 49.1% of total 222 patients on HD.31 Teles et al32 also observed that depression based on BDI was 42.7% in 96 HD patients. The different prevalence of depression in our study population compared with other studies could be due to a widely disparate set of
demographic, socioeconomic, and physical health characteristics. The high rate of depression in HD patients is multifactorial and could be explained by several reasons including uremia, underlying anemia, sexual impairment, persistent pain, changes in lifestyle due to dialysis schedules, loss of work and family, restricted diets, fear of disability, hospitalizations, and shortened lifespan.1,3,26,33 As mentioned before, we found that serum selenium levels in HD patients were significantly lower than the healthy controls after considering the age and gender effects in both groups. In a meta-analysis by Tonelli et al, the results of 46 studies from different races were as follow: 37 studies showed decreased selenium levels in HD patients compared with controls, 8 studies found no differences between selenium levels in HD patients and healthy controls, and only 1 study reported higher selenium levels in HD patients than controls.34 Although the results were inconsistent, our
ASSOCIATION OF DEPRESSION WITH SELENIUM AND NUTRITIONAL MARKERS Table 4. Correlations Between Beck Depression Score and Measured Variables in Patients on Hemodialysis Parameter Age, y Duration on HD (mo) SGA MIS Albumin (g/dL) Hb (g/dL) Selenium (mg/L) BMI (kg/m2) Weight (kg) BUN (mg/dL) Creatinine (mg/dL) Uric acid (mg/dL) Total protein (g/dL) FBS (mg/dL) TG (mg/dL) Total cholesterol (mg/dL) HDL (mg/dL) LDL (mg/dL) Ferritin (ng/mL) Total iron binding capacity (mg/dL) Iron (mcg/dL)
Correlation Coefficient
P Value
20.21 20.07 0.32 0.32 20.27 20.26 0.12 20.001 20.08 20.09 20.02 20.07 20.12 0.05 0.10 0.08 0.03 20.02 20.004 20.01 20.10
.02* .46 .001* .001* .004* .007* .19 .99 .38 .32 .80 .43 .25 .59 .31 .42 .70 .83 .96 .89 .28
BMI, body mass index; BUN, blood urea nitrogen; FBS, fasting blood sugar; Hb Hemoglobin; HD, hemodialysis; HDL, high-density lipoprotein; LDL low-density lipoprotein; MIS, malnutrition inflammation score; SGA, subjective global assessment; TG, triglyceride. *P values are statistically significant.
findings were in accordance with the majority of studies in this issue35,36 supporting lower serum selenium levels in HD patients. Wide variations in results might be because of different sample sizes, various methods of selenium measurement, confounding factors such as environmental selenium distribution, and racial differences.37 Selenium deficiency in CKD patients contributes to increased oxidative stress, activated inflammation, accelerated atherosclerosis, immune dysfunction, malnutrition, and poor cardiac function.38 Also low levels of serum selenium in HD patients might be associated with increased risk for morbidity and mortality due to infectious,17 malignant, and atherosclerosis-related cardiovascular diseases.38,39 The decreased levels of selenium in these patients could be attributed to insufficient dietary intake due to restricted food choices and inevitable losses of selenium through HD membranes.17 Table 5. Logistic Regression Models for Identifying the Association Between Depression and Measured Variables in Patients on Hemodialysis Variable
B
SE (B)
P
Age (y) SGA Hb (g/dL)
20.12 0.81 20.85
20.2 0.32 20.21
.03 ,.001 .02
B, beta; Hb, hemoglobin; SE, standard error; SGA, subjective global assessment.
5
To our knowledge, no previous studies have evaluated the association of selenium and depression in HD patients. Available data point to the fact that selenium as an antioxidant is important for normal brain and mood function.15 These results stimulate the interest in clarifying the association of selenium deficiency and depression in HD patients. In contrast to our hypothesis, as mentioned earlier, there was no difference in serum selenium levels comparing HD patients with and without depression. Also we did not find any correlation between serum selenium concentration and depression scores in HD patients. The results of the Chinese cohort of elderly healthy population were similar to our findings meaning that no significant association was found between selenium level and depressive symptoms after adjusting for cognition.15 Although the unique and complicated role of selenium in brain metabolism is demonstrated based on literature review, the impact of selenium deficiency on brain function and depressive symptoms may not be seen in short-term exposure to low serum selenium.15 Maybe the effects will be seen in long-term exposure after the complete depletion of selenium stores in brain.40 It is perhaps not surprising that no significant association was noticed between selenium deficiency and depression in HD patients of this study. The multifactorial nature of depression in HD patients should also be considered.41 Regarding the demographic characteristics, only the rate of unemployment was higher in HD patients with depression which was similar to Roozbeh et al’s report.1 Other factors such as age, sex, marital status, education level, dialysis duration, and adequacy were not significantly related to the presence of depression in HD patients. Furthermore, depressed HD patients were more malnourished with higher SGA and MIS scores and lower serum albumin levels. Similar finding was reported in the study by Li et al done in Chinese peritoneal dialysis patients. They also found a close significant association between depression and malnutrition based on MIS.18 This association could be explained through interrelated mechanisms between malnutrition and inflammation. HD patients with depression seem to have elevated serum levels of proinflammatory cytokines such as interleukin-6.42 Thus, malnourished HD patients with higher levels of inflammation and anorexia in the context of malnutrition inflammation complex syndrome show more severe symptoms of depression.43,44 Based on regression results, a significant negative association was found between depression score and age meaning that patients with greater BDI scores were significantly younger. It might be due to more severe hopelessness and loss of job and family which are among the important factors affecting depression. In addition, we found a significant reverse association between Hb and depression score. These findings were consistent with the results of the study by Kalender et al24 in which ESRD patients with depression had lower Hb and hematocrit levels. In the study by Roozbeh
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et al1 the levels of Hb were similar in both groups of HD patients with and without depression which were different from our results. In another study done by Afsar45 in stable HD patients, depression symptoms were independently related with erythropoiesis stimulating agent hyporesponsiveness index. The similar association between depression and Hb level as seen in our work was also found in earlier researches in anemic subjects other than HD patients such as elderly persons with anemia,46 women with early postpartum anemia,47 and anemic patients with acute coronary syndrome.48 The association between lower Hb levels and depression could be attributed to fatigue, decreased levels of brain oxygen, higher levels of inflammation49 due to resistance to erythropoietin,45 and vitamin B12 deficiency which are all the main features of poor health status in anemia.49 Although it was the first study that revealed the association of depression with selenium deficiency and nutritional markers in HD patients, our work had some limitations. This was a very young cohort of HD patients and results may not be generalizable to other HD populations. Further studies are needed to evaluate the association of depression with inflammatory and oxidative stress markers such as C-reactive protein, interleukin-6, tumor necrosis factor alpha, and malondialdehyde in HD patients. Evaluating quality of life through questionnaires and determining its association with depression could be helpful in future works. Regarding selenium status in HD patients some suggestions could be helpful in better interpretation. These include checking for dietary selenium intake, determining selenium levels in hair and nail samples, assessing selenium concentration in dialysis fluid, and considering selenium content of soil and water in the region of research. Also much remains to be learned about the biological mechanisms of selenium in pathophysiology of depression. Because of the cross-sectional design of this study, no causal relationship between depression and nutritional markers could be investigated. Thus, some longitudinal studies with follow-up researches might be needed.
Practical Application and Conclusions In conclusion, we found that HD patients had lower serum selenium levels compared with healthy controls. Also depression is more seen in malnourished HD patients with lower Hb levels regardless of serum selenium status. High prevalence of depression in this population of HD patients warrants more attention regarding proper treatment of depression in malnourished HD patients with the aim of improving their overall health and survival.
Acknowledgement Authors of this article have no conflict of interest to declare. This study was supported by grant from Shiraz University of Medical Sciences, Shiraz, Iran (Grant number: 93-01-84-8107). The authors would like to thank Mr. Ghasemi the personnel of the toxicology laboratory of the Razavi Hospital in Mashhad for measuring selenium.
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ASSOCIATION OF DEPRESSION WITH SELENIUM AND NUTRITIONAL MARKERS correction and a reduced palladium modifier: age-specific reference ranges. Clin Chem. 1988;34:709-714. 24. Kalender B, Corapcioglu Ozdemir A, Koroglu G. Association of depression with markers of nutrition and inflammation in chronic kidney disease and end-stage renal disease. Nephron Clin Pract. 2005;102: c115-c121. 25. Finkelstein FO, Wuerth D, Finkelstein SH. An approach to addressing depression in patients with chronic kidney disease. Blood Purif. 2010;29:121-124. 26. Santoro D, Satta E, Messina S, Costantino G, Savica V, Bellinghieri G. Pain in end-stage renal disease: a frequent and neglected clinical problem. Clin Nephrol. 2013;79:S2-S11. 27. Harris TJ, Nazir R, Khetpal P, et al. Pain, sleep disturbance and survival in hemodialysis patients. Nephrol Dial Transplant. 2012;27:758-765. 28. Hedayati SS, Minhajuddin AT, Toto RD, Morris DW, Rush AJ. Validation of depression screening scales in patients with CKD. Am J Kidney Dis. 2009;54:433-439. 29. Ossareh S, Tabrizian S, Zebarjadi M, Joodat RS. Prevalence of depression in maintenance hemodialysis patients and its correlation with adherence to medications. Iran J Kidney Dis. 2014;8:467-474. 30. Stasiak CES, Bazan KS, Kuss RS, Schuinski AFM, Baroni G. Prevalence of anxiety and depression and its comorbidities in patients with chronic kidney disease on hemodialysis and peritoneal dialysis. J Bras Nefrol. 2014;36:325-331. 31. Trbojevic-Stankovic J, Stojimirovic B, Bukumiric Z, et al. Depression and quality of sleep in maintenance hemodialysis patients. Srp Arh Celok Lek. 2014;142:437-443. 32. Teles F, Azevedo VF, Miranda CT, Miranda MP, Teixeira Mdc C, Elias RM. Depression in hemodialysis patients: the role of dialysis shift. Clinics. 2014;69:198-202. 33. Feroze U, Martin D, Reina-Patton A, Kalantar-Zadeh K, Kopple JD. Mental health, depression, and anxiety in patients on maintenance dialysis. Iran J Kidney Dis. 2010;4:173-180. 34. Tonelli M, Wiebe N, Hemmelgarn B, et al. Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med. 2009;7:25. 35. Kallistratos G, Evangelou A, Seferiadis K, Vezyraki P, Barboutis K. Selenium and haemodialysis: serum selenium levels in healthy persons, non-cancer and cancer patients with chronic renal failure. Nephron. 1985;41:217-222. 36. Bogye G, Tompos G, Alfthan G. Selenium depletion in hemodialysis patients treated with polysulfone membranes. Nephron. 2000;84:119-123.
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37. Fujishima Y, Ohsawa M, Itai K, et al. Serum selenium levels in hemodialysis patients are significantly lower than those in healthy controls. Blood Purif. 2011;32:43-47. 38. Iglesias P, Selgas R, Romero S, Dıez JJ. Selenium and kidney disease. J Nephrol. 2013;26:266-272. 39. del Moral LM, Agil A, Navarro-Alarc on M, de la Serrana HL-G, Palomares-Bayo M, Oliveras-L opez MJ. Altered serum selenium and uric acid levels and dyslipidemia in hemodialysis patients could be associated with enhanced cardiovascular risk. Biol Trace Elem Res. 2011;144:496-503. 40. Behne D, Hilmert H, Scheid S, Gessner H, Elger W. Evidence for specific selenium target tissues and new biologically important selenoproteins. Biochim Biophys Acta. 1988;966:12-21. 41. Roman A, Kreiner G, Nalepa I. Macrophages and depression–a misalliance or well-arranged marriage? Pharmacol Rep. 2013;65:1663-1672. 42. Taraz M, Taraz S, Dashti-Khavidaki S. Association between depression and inflammatory/anti-inflammatory cytokines in chronic kidney disease and end-stage renal disease patients: a review of literature [published online ahead of print July 15 2014]. Hemodial Int., http://www.ncbi.nlm.nih.gov/ pubmed/25040322. Accessed July 15, 2014. 43. Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis. 2003;42:864-881. 44. Bossola M, Ciciarelli C, Di Stasio E, et al. Relationship between appetite and symptoms of depression and anxiety in patients on chronic hemodialysis. J Ren Nutr. 2012;22:27-33. 45. Afsar B. The relationship between depressive symptoms and erythropoietin resistance in stable hemodialysis patients with adequate iron stores. Int J Artif Organs. 2013;36:314-319. 46. Onder G, Penninx BW, Cesari M, et al. Anemia is associated with depression in older adults: results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2005;60:1168-1172. 47. Corwin EJ, Murray-Kolb LE, Beard JL. Low hemoglobin level is a risk factor for postpartum depression. J Nutr. 2003;133:4139-4142. 48. Steptoe A, Wikman A, Molloy GJ, Kaski JC. Anaemia and the development of depressive symptoms following acute coronary syndrome: longitudinal clinical observational study. BMJ Open. 2012;2:e000551. 49. Lever-van Milligen BA, Vogelzangs N, Smit JH, Penninx BW. Hemoglobin levels in persons with depressive and/or anxiety disorders. J psychosom Res. 2014;76:317-321.
Association of Depression With Selenium Deficiency and Nutritional Markers in the Patients with End-Stage Renal Disease on Hemodialysis Maryam Ekramzadeh, PhD,* Zohreh Mazloom, PhD,* and Mohammadmahdi Sagheb, MD† Objective: Depression is considered as the most common psychological problem in hemodialysis (HD) patients. As there is little evidence regarding the association of depression with serum selenium level as an antioxidant in these patients, the current survey investigates the possible relationship between depression and nutritional status including serum selenium levels. Design: Cross-sectional study. Setting and Subjects: A total of 110 HD patients and 40 healthy controls were enrolled in the study. The patients were in the age range of 18 to 85 years, who had been on hemodialysis for at least 3 months without any acute illness. Main Outcome Measure: Beck Depression Inventory was used for assessing the severity of depression. Malnutrition was evaluated through subjective global assessment (SGA) and malnutrition inflammation score (MIS). Serum selenium levels and routine laboratory markers were measured from fasting samples. Results: Sixty-two percent of the patients had some degree of depression based on Beck Depression Inventory score. HD patients were considered to be selenium deficient after comparing the mean value of serum selenium between the patients and controls (P , .001). No significant difference was found in serum selenium levels between depressed HD patients and the rest of patients without depression. The mean level of SGA and MIS in the depressed patients was significantly higher than the rest of patients (P 5 .03 and P 5 .04, respectively). Also lower levels of hemoglobin and serum albumin were significantly seen in depressed patients compared with nondepressed ones (P 5 .004 and P 5 .04, respectively). Conclusions: Although the HD patients in this study were selenium deficient, no significant association was found between depression and selenium. In addition, depression was more prevalent in malnourished HD patients with higher SGA and MIS scores and lower serum albumin and hemoglobin levels. Ó 2015 by the National Kidney Foundation, Inc. All rights reserved.
Introduction
D
EPRESSION IS THE most common psychological problem in the end-stage renal disease (ESRD) patients undergoing hemodialysis (HD).1,2 HD affects the life of patients in different aspects of social, physical, occupational, and personal. Thus, depression may be a normal response to these situations in HD patients.3 A mutual link has been found between depression and chronic disease state in the way that depression could have a great impact on nutrition, appetite, and immune system.1,4 It has been demonstrated that depression is an important predictor of morbidity,5 mortality,6-10 and lower quality of life11 in patients undergoing HD. Depression as an inflammatory disease characterized by accumula* Department of Clinical Nutrition, Shiraz School of Nutrition & Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. † Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Financial Disclosure: See Acknowledgments on page XXX. Address correspondence to Zohreh Mazloom, PhD, Department of Clinical Nutrition, Shiraz School of Nutrition & Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. E-mail: [email protected] Ó 2015 by the National Kidney Foundation, Inc. All rights reserved. 1051-2276/$36.00 http://dx.doi.org/10.1053/j.jrn.2014.12.005
Journal of Renal Nutrition, Vol -, No - (-), 2015: pp 1-7
tion of highly reactive oxygen species12,13 is associated with an increased risk of cardiovascular disease and atherosclerosis.14 Selenium as an essential antioxidant has a modulatory role in brain function and mood stabilization through attenuation of inflammation.12,13,15,16 Previous studies have demonstrated that serum levels of selenium are decreased in HD patients because of insufficient dietary intake or losses through HD membranes.17 Depression is also linked with malnutrition in the way that it is more severe in depressed dialysis patients.18 Despite the high prevalence and importance of depression in HD population, many patients often go unnoticed by the health care professionals.3 The Beck’s Depression Inventory (BDI) is a standard self-administered questionnaire for screening HD patients with depression.1,2 Although there is a large body of literature on depression in chronic kidney disease (CKD), no study evaluated the association of depression with selenium level, nutritional and biochemical markers in HD patients. In addition, a few studies examining the relationship between selenium and depression in healthy population12,15 have yielded inconsistent results, and none of these studies considered the association of selenium with depression in HD patients. The aim of this study was to elucidate the possible relationship between depression and serum 1
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EKRAMZADEH ET AL
selenium and nutritional and biochemical parameters in a group of patients undergoing HD.
Methods Patient Selection The present study included 110 patients with ESRD on HD from the outpatient clinics of our hospital. Forty healthy control subjects without any endocrine or metabolic disease were also recruited from hospital personnel with the aim of comparing depression score and serum selenium levels between healthy population and HD patients. The data were collected from August 1 to December1, 2013. All the participants gave their informed consent in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The patients were in the age range of 18 to 85 years, who had been on HD for at least 3 months without any acute illness. All enrolled patients were on HD 3 to 3 times a week for 3 hours using low flux dialysis filters with polysulfone/polyamide membranes and reverse osmosis purified water and bicarbonatecontaining dialysis solution. The subjects who took antidepressants, oral iron, vitamin B12, folate, and antioxidant supplements were excluded from the study. Clinical and Nutritional Assessment Demographic data (age, gender, level of education, marital status, employment, and duration of HD) were collected through questionnaires filled by the main investigator. The BDI scoring system1,2,19,20 was used to evaluate the severity of depression in HD patients. The BDI is a standard 21-question multiple choice questionnaire with a self-report inventory which measures the common clinical symptoms of depression like feelings of hopelessness, sadness, anhedonia, guilt, fatigue, and also changes in sleep, weight, appetite, and libido. The value of each component ranges from 0 to 3. At the end, the sum of scores was as follows: 0 to 9: no depression; 10 to 13: borderline; 14 to 19: mild depression; 20 to 28: moderate depression; and 29 to 63: severe depression. Higher scores were indicative of more severe depression. The questions were read and replied by each patient, and the total score was compared with a key to decide whether the patient was categorized as depressed or not. BDI questionnaire was filled for both groups of HD patients and healthy control subjects. Valid nutritional markers such as subjective global assessment (SGA) and malnutrition inflammation score (MIS) were checked in all patients through face-to-face interview. SGA questionnaire was a useful tool for evaluating nutritional status in HD patients. It includes questions on physical examination (muscle and subcutaneous fat wasting, edema), and nutritional history (weight change during the preceding 2 weeks and 6 months, appetite, food intake, and gastrointestinal symptoms). The overall status was interpreted based on the sum of scores as follows (the score for each item from 0 to 5): a score of less than 10 well-
nourished, 10 to 17 mildly to moderately malnourished, and higher than 17 severely malnourished.21 MIS scoring system is more quantitative and complete than SGA. It had all the similar parts explained earlier in SGA. It also included 2 nutritional laboratory markers (albumin and transferrin). Each item scores from 0 to 3. The sum of scores of all 10 components could be a good indicator of nutritional status. The higher the score was, the more severe the malnutrition and inflammation was.22 Serum selenium levels were measured in both groups of healthy controls and HD patients from fasting serum samples using graphite furnace atomic absorption spectrometry method.23 The blood samples were taken from the patient’s arm used for HD cannulae just before the beginning of the HD session. The serum in both groups of healthy and HD patients was obtained by centrifugation at 3000 g/minute for 5 minutes and stored at 270 C in the laboratory of the local hospital for further analysis. Other routine laboratory markers (as listed in Table 3) such as blood urea nitrogen, creatinine, albumin, hemoglobin (Hb), serum iron, ferritin, and lipid profile were assessed for each patient using standard automated techniques in facilities.
Selenium Measurement Settings The wavelength used was 196.0 nm with slit width 1.0 nm and lamp current: 10.0 mA. Calibration mode was standard additions. Adding inorganic selenium to sera before sample reduction yielded valid calibration slopes by standard additions. The final furnace conditions and temperature program for drying of serum for selenium detection are depicted in Table 1. Statistical Analysis Data were analyzed using SPSS 18 (SPSS Inc., Chicago, IL) statistical software package. All the data were assessed for normality of distribution, using the Kolmogorov–Smirnov test. Depression score in 2 groups of HD patients and healthy controls with regard to confounding factors (age, sex, marriage, job, education level) were compared using covariance analysis. To compare variables according to the Beck depression score among HD patients, Table 1. Standard Addition Steps in Measuring Serum Selenium Levels Gas Step Temp Flow Number Degree (C) Time (s) (L/min) 1 2 3 4 5 6 7 8 9
85 95 120 400 1,000 1,000 2,600 2,600 2,600
5.0 40.0 10.0 5.0 1.0 2.0 0.8 2.0 2.0
3.0 3.0 3.0 3.0 3.0 0.0 0.0 0.0 3.0
Gas Type Normal Normal Normal Normal Normal Normal Normal Normal Normal
Read Store No No No No No No Yes Yes No
No No No No No Yes Yes Yes Yes
ASSOCIATION OF DEPRESSION WITH SELENIUM AND NUTRITIONAL MARKERS
independent sample t test, Mann-Whitney U test, and c2 test were used. The correlations were first calculated by the Pearson correlation test and then the variables with significant coefficients were tested again in backward multivariate regression model. P values ,.05 were considered statistically significant.
Results A total of 110 HD patients and 40 healthy controls participated in this cross-sectional study. The demographic characteristics of healthy subjects could be seen in Table 2. The mean age of the HD patients was 47.81 6 14.80 years (mean 6 standard deviation). In our study, 38.9% of the patients were female and 70% were married. Seventy-two percent of them were unemployed, whereas 57.4% of the total patients had education of less than high school. The mean duration on HD and efficacy of dialysis (KT/V) were 34.5 6 3.81 months and 1.36 6 0.02 (mean 6 standard error) respectively. The 2 main causes of renal failure in this population were diabetes (38.9%) and hypertension (37%). Signs of depression were found in 62% of all the patients. Among them 28.7% had mild depression (BDI 5 14–19), 23.1% had moderate depression (BDI 5 20–28), and 10.2% had severe depression (BDI $ 29). The average BDI was 16.81 6 9.27 (range 0–56). Serum selenium levels and depression score based on BDI were compared between HD patients and healthy subjects. As shown in Table 2, serum selenium levels in HD patients were significantly lower than healthy controls (P , .001). Regarding depression, the mean BDI score in HD patients (16.99 6 9.21) was significantly higher than healthy individuals (11.46 6 8.87) (P 5.009) after adjusting for age (P 5.26), gender (P 5.42), marital status (P 5.19), employment (P 5 .09), and education level (P 5 .86) as confounding factors using analysis of covariance. The HD patients were divided into 2 groups based on Beck depression score: those with normal BDI score (nondepressed patients, group 1: BDI ,10, n 5 30) and those with some degrees of depression (borderline to severe) (HD patients with clinical depression, group 2: BDI $ 10, n 5 80). Higher BDI scores in group 2 were indicTable 2. Selenium Levels and Beck Depression Scores of Hemodialysis Patients and Controls Variable
Hemodialysis (n 5 110)
Controls (n 5 40)
P Value
Selenium (mg/L) 94.78 6 10.80 111.007 6 15.93 ,.001* Beck depression 16.99 6 9.21 11.46 6 8.87 .009† score Age (y) 47.81 6 14.80 45.65 6 9.87 .09‡ Female (%) 38.9 50 .22‡ The data are shown as mean 6 standard deviation. *P , .05 by t test. †P , .05 by analysis of covariance. ‡Other 2 insignificant P values by t test.
3
ative of more severe depressive symptoms, whereas the patients in group 1 had no clinical depression. Selenium levels, nutritional markers, and other biochemical factors were compared between the 2 groups. The results have been shown in Table 3. The HD patients with depression in group 2 had significantly higher SGA (P 5 .03) and MIS (P 5 .04) scores. In addition, levels of Hb (P 5 .004) and serum albumin (P 5 .04) were significantly lower in depressed HD patients in group 2. Also rate of employment was significantly lower in HD patients with higher BDI scores (P 5 .03). But no significant difference was found regarding serum selenium levels between 2 groups. As seen in Table 3, other demographic characteristics and biochemical parameters were not significantly different when comparing the 2 groups. The correlations between Beck depression score and measured variables are shown in Table 4. The variables with significant coefficient were age (r 5 20.21, P 5 .02), SGA (r 5 0.32, P 5 .001), MIS (r 5 0.32, P 5 .001), Hb (r 5 20.26, P 5 .007), and albumin (r 5 20.27, P 5 .004). After analyzing these significant variables in regression models, results showed no correlation between BDI score and clinical variables except for age (P 5 .03), SGA (P , .001), and Hb (P 5 .02) (Table 5).
Discussion The results of this study revealed new findings in HD patients regarding the association of selenium status with depression. Our results did not reveal an association between selenium level as a potential novel modifiable factor in the primary prevention of depression and BDI score but rather tested whether there was an association. Although the patients in this study were selenium deficient compared with healthy controls, we found no difference in serum selenium concentration between the HD patients with depression and the normal ones without depression based on Beck depression score. In addition, similar to the results of previous studies18,24 we found that depressed HD patients with greater BDI scores had more severe malnutrition based on SGA, MIS, serum albumin, and Hb levels meaning that HD patients with depression were more malnourished and anemic compared with the ones without depression. Clinical depression is emerging as the most common and significant psychological problem in patients with ESRD undergoing HD.1,2,25 HD patients with clinically significant depression have lower quality of life and higher rates of morbidity and mortality.5,9-11 Depression in HD patients is also related to increased perception of pain which in turn may lead to more discomfort and mortality rate. On the other hand, chronic pain which is a prevalent characteristic in HD patients is associated with increased depression and lower quality of life by altering brain chemistry.26,27As BDI scores of $11 have a sensitivity and specificity of about 90%, this questionnaire
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EKRAMZADEH ET AL
Table 3. Clinical and Nutritional Parameters in Hemodialysis Patients Based on Beck Depression Scores Parameter Age (y) Duration of dialysis (mo) Gender (female %) Education level of less than high school (%) Rate of marriage (%) Rate of employment (%) Selenium (mg/L) SGA MIS Albumin (g/dL) Hb (g/dL) BMI (kg/m2) Weight (kg) BUN (mg/dL) Creatinine (mg/dL) Kt/V Uric acid (mg/dL) Total protein (g/dL) Calcium (mg/dL) Phosphorus (mg/dL) PTH (pg/dL) Potassium (mg/dL) Sodium (mEq/L) FBS (mg/dL) TG (mg/dL) Total cholesterol (mg/dL) HDL (mg/dL) LDL (mg/dL) AST (IU/L) ALT (IU/L) Alkaline phosphatase (IU/L) Ferritin (ng/mL) Total iron binding capacity (mg/dL) Iron (mcg/dL)
Group 1 (BDI , 10, n 5 30)
Group 2 (BDI $ 10, n 5 80)
52.38 6 2.6 31.44 6 6.13 30.8 46.2
46.41 6 1.69 35.46 6 4.84 40.7 60
81.5 44.4 94.23 6 2.33 11.61 6 0.63 6.52 6 0.68 4.52 6 0.08 13.80 6 0.46 23.93 6 1.15 69.46 6 2.96 48.82 6 3.28 7.07 6 0.45 1.35 6 0.02 5.03 6 0.2 7.11 6 0.2 8.96 6 0.15 5.3 6 0.22 311.97 6 73.71 5.40 6 0.15 139.82 6 0.67 116.47 6 12.66 153.39 6 10.6 168.60 6 7.10 36 6 1.49 104.56 6 6.89 16.69 6 1.47 17.60 6 1.92 282.56 6 28.3 533.16 6 113.42 268.95 6 14.88 82.17 6 8.50
66.7 23.5 94.33 6 1.10 13.36 6 0.41 8.28 6 0.43 4.27 6 0.06 12.25 6 0.25 24.03 6 0.58 65.73 6 1.62 46.65 6 1.94 8.18 6 1.28 1.42 6 0.05 4.73 6 0.11 7.14 6 0.09 8.97 6 0.07 5.12 6 0.15 374.05 6 35.99 5.36 6 0.08 139.87 6 0.35 119.40 6 9.15 169.44 6 10.61 169.15 6 5.01 35.85 6 1.20 95.87 6 4.29 14.02 6 0.86 14.33 6 1.13 417.77 6 48.22 599.16 6 57.30 267.76 6 7.38 73.05 6 3.65
P Value .07 .66 .36 .5 .14 .03 .96 .03* .04* .04* .004* .93 .26 .58 .64 .46 .22 .9 .99 .55 .42 .79 .95 .87 .42 .95 .95 .31 .13 .15 .13 .58 .94 .26
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BDI, Beck Depression Inventory; BMI, body mass index; BUN, blood urea nitrogen; FBS, fasting blood sugar; Hb Hemoglobin; HDL, high-density lipoprotein; LDL low-density lipoprotein; MIS, malnutrition inflammation score; PTH (Parathyroid Hormone); SGA, subjective global assessment; TG, triglyceride. The data are expressed as mean 6 mean standard error. *P values are statistically significant.
is used as a valid screening tool for diagnosing depression in patients with CKD.28 The prevalence of depression in our patients was 62%. This high rate was somehow similar to the reports of the study done by Roozbeh et al1 in which 76% of the HD patients had some degree of depression based on BDI score. In other studies, the prevalence of depression was lower than ours. In the work done by Ossareh et al29, depression was documented in 40.7% of 150 maintenance HD patients according to BDI. In the study by Stasiak et al30, depression was found in 22.6% of 128 HD patients based on BDI. The results of another study showed that depression signs of BDI were found in 49.1% of total 222 patients on HD.31 Teles et al32 also observed that depression based on BDI was 42.7% in 96 HD patients. The different prevalence of depression in our study population compared with other studies could be due to a widely disparate set of
demographic, socioeconomic, and physical health characteristics. The high rate of depression in HD patients is multifactorial and could be explained by several reasons including uremia, underlying anemia, sexual impairment, persistent pain, changes in lifestyle due to dialysis schedules, loss of work and family, restricted diets, fear of disability, hospitalizations, and shortened lifespan.1,3,26,33 As mentioned before, we found that serum selenium levels in HD patients were significantly lower than the healthy controls after considering the age and gender effects in both groups. In a meta-analysis by Tonelli et al, the results of 46 studies from different races were as follow: 37 studies showed decreased selenium levels in HD patients compared with controls, 8 studies found no differences between selenium levels in HD patients and healthy controls, and only 1 study reported higher selenium levels in HD patients than controls.34 Although the results were inconsistent, our
ASSOCIATION OF DEPRESSION WITH SELENIUM AND NUTRITIONAL MARKERS Table 4. Correlations Between Beck Depression Score and Measured Variables in Patients on Hemodialysis Parameter Age, y Duration on HD (mo) SGA MIS Albumin (g/dL) Hb (g/dL) Selenium (mg/L) BMI (kg/m2) Weight (kg) BUN (mg/dL) Creatinine (mg/dL) Uric acid (mg/dL) Total protein (g/dL) FBS (mg/dL) TG (mg/dL) Total cholesterol (mg/dL) HDL (mg/dL) LDL (mg/dL) Ferritin (ng/mL) Total iron binding capacity (mg/dL) Iron (mcg/dL)
Correlation Coefficient
P Value
20.21 20.07 0.32 0.32 20.27 20.26 0.12 20.001 20.08 20.09 20.02 20.07 20.12 0.05 0.10 0.08 0.03 20.02 20.004 20.01 20.10
.02* .46 .001* .001* .004* .007* .19 .99 .38 .32 .80 .43 .25 .59 .31 .42 .70 .83 .96 .89 .28
BMI, body mass index; BUN, blood urea nitrogen; FBS, fasting blood sugar; Hb Hemoglobin; HD, hemodialysis; HDL, high-density lipoprotein; LDL low-density lipoprotein; MIS, malnutrition inflammation score; SGA, subjective global assessment; TG, triglyceride. *P values are statistically significant.
findings were in accordance with the majority of studies in this issue35,36 supporting lower serum selenium levels in HD patients. Wide variations in results might be because of different sample sizes, various methods of selenium measurement, confounding factors such as environmental selenium distribution, and racial differences.37 Selenium deficiency in CKD patients contributes to increased oxidative stress, activated inflammation, accelerated atherosclerosis, immune dysfunction, malnutrition, and poor cardiac function.38 Also low levels of serum selenium in HD patients might be associated with increased risk for morbidity and mortality due to infectious,17 malignant, and atherosclerosis-related cardiovascular diseases.38,39 The decreased levels of selenium in these patients could be attributed to insufficient dietary intake due to restricted food choices and inevitable losses of selenium through HD membranes.17 Table 5. Logistic Regression Models for Identifying the Association Between Depression and Measured Variables in Patients on Hemodialysis Variable
B
SE (B)
P
Age (y) SGA Hb (g/dL)
20.12 0.81 20.85
20.2 0.32 20.21
.03 ,.001 .02
B, beta; Hb, hemoglobin; SE, standard error; SGA, subjective global assessment.
5
To our knowledge, no previous studies have evaluated the association of selenium and depression in HD patients. Available data point to the fact that selenium as an antioxidant is important for normal brain and mood function.15 These results stimulate the interest in clarifying the association of selenium deficiency and depression in HD patients. In contrast to our hypothesis, as mentioned earlier, there was no difference in serum selenium levels comparing HD patients with and without depression. Also we did not find any correlation between serum selenium concentration and depression scores in HD patients. The results of the Chinese cohort of elderly healthy population were similar to our findings meaning that no significant association was found between selenium level and depressive symptoms after adjusting for cognition.15 Although the unique and complicated role of selenium in brain metabolism is demonstrated based on literature review, the impact of selenium deficiency on brain function and depressive symptoms may not be seen in short-term exposure to low serum selenium.15 Maybe the effects will be seen in long-term exposure after the complete depletion of selenium stores in brain.40 It is perhaps not surprising that no significant association was noticed between selenium deficiency and depression in HD patients of this study. The multifactorial nature of depression in HD patients should also be considered.41 Regarding the demographic characteristics, only the rate of unemployment was higher in HD patients with depression which was similar to Roozbeh et al’s report.1 Other factors such as age, sex, marital status, education level, dialysis duration, and adequacy were not significantly related to the presence of depression in HD patients. Furthermore, depressed HD patients were more malnourished with higher SGA and MIS scores and lower serum albumin levels. Similar finding was reported in the study by Li et al done in Chinese peritoneal dialysis patients. They also found a close significant association between depression and malnutrition based on MIS.18 This association could be explained through interrelated mechanisms between malnutrition and inflammation. HD patients with depression seem to have elevated serum levels of proinflammatory cytokines such as interleukin-6.42 Thus, malnourished HD patients with higher levels of inflammation and anorexia in the context of malnutrition inflammation complex syndrome show more severe symptoms of depression.43,44 Based on regression results, a significant negative association was found between depression score and age meaning that patients with greater BDI scores were significantly younger. It might be due to more severe hopelessness and loss of job and family which are among the important factors affecting depression. In addition, we found a significant reverse association between Hb and depression score. These findings were consistent with the results of the study by Kalender et al24 in which ESRD patients with depression had lower Hb and hematocrit levels. In the study by Roozbeh
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et al1 the levels of Hb were similar in both groups of HD patients with and without depression which were different from our results. In another study done by Afsar45 in stable HD patients, depression symptoms were independently related with erythropoiesis stimulating agent hyporesponsiveness index. The similar association between depression and Hb level as seen in our work was also found in earlier researches in anemic subjects other than HD patients such as elderly persons with anemia,46 women with early postpartum anemia,47 and anemic patients with acute coronary syndrome.48 The association between lower Hb levels and depression could be attributed to fatigue, decreased levels of brain oxygen, higher levels of inflammation49 due to resistance to erythropoietin,45 and vitamin B12 deficiency which are all the main features of poor health status in anemia.49 Although it was the first study that revealed the association of depression with selenium deficiency and nutritional markers in HD patients, our work had some limitations. This was a very young cohort of HD patients and results may not be generalizable to other HD populations. Further studies are needed to evaluate the association of depression with inflammatory and oxidative stress markers such as C-reactive protein, interleukin-6, tumor necrosis factor alpha, and malondialdehyde in HD patients. Evaluating quality of life through questionnaires and determining its association with depression could be helpful in future works. Regarding selenium status in HD patients some suggestions could be helpful in better interpretation. These include checking for dietary selenium intake, determining selenium levels in hair and nail samples, assessing selenium concentration in dialysis fluid, and considering selenium content of soil and water in the region of research. Also much remains to be learned about the biological mechanisms of selenium in pathophysiology of depression. Because of the cross-sectional design of this study, no causal relationship between depression and nutritional markers could be investigated. Thus, some longitudinal studies with follow-up researches might be needed.
Practical Application and Conclusions In conclusion, we found that HD patients had lower serum selenium levels compared with healthy controls. Also depression is more seen in malnourished HD patients with lower Hb levels regardless of serum selenium status. High prevalence of depression in this population of HD patients warrants more attention regarding proper treatment of depression in malnourished HD patients with the aim of improving their overall health and survival.
Acknowledgement Authors of this article have no conflict of interest to declare. This study was supported by grant from Shiraz University of Medical Sciences, Shiraz, Iran (Grant number: 93-01-84-8107). The authors would like to thank Mr. Ghasemi the personnel of the toxicology laboratory of the Razavi Hospital in Mashhad for measuring selenium.
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