jurnal lengkap : Depresi Dengan Defisiensi Selenium dan Gizi Pasien dengan ESRD yang mnejalni Hemodialisis

1. 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
DEPRESSION IS THE most common psychological
problem in the end-stage renal disease (ESRD) pa-
tients 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 sys-
tem.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. Depres-
sion as an inflammatory disease characterized by accumula-
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
Depres-
sion 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 pop-
ulation, 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
*
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: zhmazloom@gmail.com
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 1

2. 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 meta-
bolic disease were also recruited from hospital personnel
with the aim of comparing depression score and serum se-
lenium 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 bicarbonate-
containing dialysis solution. The subjects who took antide-
pressants, 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 investi-
gator. 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 clin-
ical 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 fol-
lows: 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 assess-
ment (SGA) and malnutrition inflammation score (MIS)
were checked in all patients through face-to-face interview.
SGA questionnaire was a useful tool for evaluating nutri-
tional status in HD patients. It includes questions on phys-
ical 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 in-
terpreted 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 (al-
bumin and transferrin). Each item scores from 0 to 3. The
sum of scores of all 10 components could be a good indica-
tor 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 sam-
ples 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 labora-
tory markers (as listed in Table 3) such as blood urea nitro-
gen, 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
Step
Number
Temp
Degree (C) Time (s)
Gas
Flow
(L/min)
Gas
Type Read Store
1 85 5.0 3.0 Normal No No
2 95 40.0 3.0 Normal No No
3 120 10.0 3.0 Normal No No
4 400 5.0 3.0 Normal No No
5 1,000 1.0 3.0 Normal No No
6 1,000 2.0 0.0 Normal No Yes
7 2,600 0.8 0.0 Normal Yes Yes
8 2,600 2.0 0.0 Normal Yes Yes
9 2,600 2.0 3.0 Normal No Yes
EKRAMZADEH ET AL2

3. 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 sig-
nificant coefficients were tested again in backward multi-
variate 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 pa-
tients 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 sub-
jects. As shown in Table 2, serum selenium levels in HD pa-
tients 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 se-
vere) (HD patients with clinical depression, group 2: BDI
$ 10, n 5 80). Higher BDI scores in group 2 were indic-
ative of more severe depressive symptoms, whereas the pa-
tients 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 pa-
tients regarding the association of selenium status with
depression. Our results did not reveal an association be-
tween 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.26,27
As BDI scores of $11 have a
sensitivity and specificity of about 90%, this questionnaire
Table 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
score
16.99 6 9.21 11.46 6 8.87 .009†
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.
ASSOCIATION OF DEPRESSION WITH SELENIUM AND NUTRITIONAL MARKERS 3

4. 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 pa-
tients 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 ac-
cording 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 charac-
teristics. 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 sele-
nium 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
Table 3. Clinical and Nutritional Parameters in Hemodialysis Patients Based on Beck Depression Scores
Parameter Group 1 (BDI , 10, n 5 30) Group 2 (BDI $ 10, n 5 80) P Value
Age (y) 52.38 6 2.6 46.41 6 1.69 .07
Duration of dialysis (mo) 31.44 6 6.13 35.46 6 4.84 .66
Gender (female %) 30.8 40.7 .36
Education level of less than high school
(%)
46.2 60 .5
Rate of marriage (%) 81.5 66.7 .14
Rate of employment (%) 44.4 23.5 .03
Selenium (mg/L) 94.23 6 2.33 94.33 6 1.10 .96
SGA 11.61 6 0.63 13.36 6 0.41 .03*
MIS 6.52 6 0.68 8.28 6 0.43 .04*
Albumin (g/dL) 4.52 6 0.08 4.27 6 0.06 .04*
Hb (g/dL) 13.80 6 0.46 12.25 6 0.25 .004*
BMI (kg/m2
) 23.93 6 1.15 24.03 6 0.58 .93
Weight (kg) 69.46 6 2.96 65.73 6 1.62 .26
BUN (mg/dL) 48.82 6 3.28 46.65 6 1.94 .58
Creatinine (mg/dL) 7.07 6 0.45 8.18 6 1.28 .64
Kt/V 1.35 6 0.02 1.42 6 0.05 .46
Uric acid (mg/dL) 5.03 6 0.2 4.73 6 0.11 .22
Total protein (g/dL) 7.11 6 0.2 7.14 6 0.09 .9
Calcium (mg/dL) 8.96 6 0.15 8.97 6 0.07 .99
Phosphorus (mg/dL) 5.3 6 0.22 5.12 6 0.15 .55
PTH (pg/dL) 311.97 6 73.71 374.05 6 35.99 .42
Potassium (mg/dL) 5.40 6 0.15 5.36 6 0.08 .79
Sodium (mEq/L) 139.82 6 0.67 139.87 6 0.35 .95
FBS (mg/dL) 116.47 6 12.66 119.40 6 9.15 .87
TG (mg/dL) 153.39 6 10.6 169.44 6 10.61 .42
Total cholesterol (mg/dL) 168.60 6 7.10 169.15 6 5.01 .95
HDL (mg/dL) 36 6 1.49 35.85 6 1.20 .95
LDL (mg/dL) 104.56 6 6.89 95.87 6 4.29 .31
AST (IU/L) 16.69 6 1.47 14.02 6 0.86 .13
ALT (IU/L) 17.60 6 1.92 14.33 6 1.13 .15
Alkaline phosphatase (IU/L) 282.56 6 28.3 417.77 6 48.22 .13
Ferritin (ng/mL) 533.16 6 113.42 599.16 6 57.30 .58
Total iron binding capacity (mg/dL) 268.95 6 14.88 267.76 6 7.38 .94
Iron (mcg/dL) 82.17 6 8.50 73.05 6 3.65 .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.
EKRAMZADEH ET AL4

5. 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 oxida-
tive stress, activated inflammation, accelerated atheroscle-
rosis, 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
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 antiox-
idant is important for normal brain and mood function.15
These results stimulate the interest in clarifying the associ-
ation 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 concen-
tration 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 associa-
tion was found between selenium level and depressive
symptoms after adjusting for cognition.15
Although the
unique and complicated role of selenium in brain meta-
bolism is demonstrated based on literature review, the
impact of selenium deficiency on brain function and
depressive symptoms may not be seen in short-term expo-
sure 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 sele-
nium deficiency and depression in HD patients of this
study. The multifactorial nature of depression in HD pa-
tients should also be considered.41
Regarding the demographic characteristics, only the rate
of unemployment was higher in HD patients with depres-
sion which was similar to Roozbeh et al’s report.1
Other fac-
tors 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 associa-
tion 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 Ka-
lender et al24
in which ESRD patients with depression had
lower Hb and hematocrit levels. In the study by Roozbeh
Table 4. Correlations Between Beck Depression Score and
Measured Variables in Patients on Hemodialysis
Parameter
Correlation
Coefficient P Value
Age, y 20.21 .02*
Duration on HD (mo) 20.07 .46
SGA 0.32 .001*
MIS 0.32 .001*
Albumin (g/dL) 20.27 .004*
Hb (g/dL) 20.26 .007*
Selenium (mg/L) 0.12 .19
BMI (kg/m2
) 20.001 .99
Weight (kg) 20.08 .38
BUN (mg/dL) 20.09 .32
Creatinine (mg/dL) 20.02 .80
Uric acid (mg/dL) 20.07 .43
Total protein (g/dL) 20.12 .25
FBS (mg/dL) 0.05 .59
TG (mg/dL) 0.10 .31
Total cholesterol (mg/dL) 0.08 .42
HDL (mg/dL) 0.03 .70
LDL (mg/dL) 20.02 .83
Ferritin (ng/mL) 20.004 .96
Total iron binding capacity (mg/dL) 20.01 .89
Iron (mcg/dL) 20.10 .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 inflamma-
tion score; SGA, subjective global assessment; TG, triglyceride.
*P values are statistically significant.
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) 20.12 20.2 .03
SGA 0.81 0.32 ,.001
Hb (g/dL) 20.85 20.21 .02
B, beta; Hb, hemoglobin; SE, standard error; SGA, subjective
global assessment.
ASSOCIATION OF DEPRESSION WITH SELENIUM AND NUTRITIONAL MARKERS 5

6. et al1
the levels of Hb were similar in both groups of HD pa-
tients 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 hyporespon-
siveness index. The similar association between depression
and Hb level as seen in our work was also found in earlier re-
searches in anemic subjects other than HD patients such as
elderly persons with anemia,46
women with early post-
partum 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 resis-
tance 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 associa-
tion 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 sug-
gestions 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 mecha-
nisms 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 pa-
tients 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 labo-
ratory of the Razavi Hospital in Mashhad for measuring selenium.
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