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Optimal Serum Selenium Concentrations Are Associated With Lower Depressive Symptoms and Negative Mood Among Young Adults
Optimal Serum Selenium Concentrations Are Associated With Lower Depressive Symptoms and Negative Mood Among Young Adults
Optimal Serum Selenium Concentrations Are Associated With Lower Depressive Symptoms and Negative Mood Among Young Adults
Abstract
Background: There is evidence that low, and possibly high, selenium status is associated with depressed mood. More
evidence is needed to determine whether this pattern occurs in young adults with a wide range of serum concentrations of
selenium.
Objective: The aim of this study was to determine if serum selenium concentration is associated with depressive
symptoms and daily mood states in young adults.
Methods: A total of 978 young adults (aged 1725 y) completed the Center for Epidemiological StudiesDepression scale and
reported their negative and positive mood daily for 13 d using an Internet diary. Serum selenium concentration was determined
by inductively coupled plasma mass spectrometry. ANCOVA and regression models tested the linear and curvilinear
associations between decile of serum selenium concentration and mood outcomes, controlling for age, gender, ethnicity, BMI,
and weekly alcohol intake. Smoking and childhood socioeconomic status were further controlled in a subset of participants.
Results: The mean 6 SD serum selenium concentration was 82 6 18 mg/L and ranged from 49 to 450 mg/L. Participants
with the lowest serum selenium concentration (62 6 4 mg/L; decile 1) and, to a lesser extent, those with the highest serum
selenium concentration (110 6 38 mg/L; decile 10) had significantly greater adjusted depressive symptoms than did
participants with midrange serum selenium concentrations (82 6 1 to 85 6 1 mg/L; deciles 6 and 7). Depressive
symptomatology was lowest at a selenium concentration of ;85 mg/L. Patterns for negative mood were similar but more
U-shaped. Positive mood showed an inverse U-shaped association with selenium, but this pattern was less consistent
than depressive symptoms or negative mood.
Conclusions: In young adults, an optimal range of serum selenium between ;82 and 85 mg/L was associated with reduced risk
of depressive symptomatology. This range approximates the values at which glutathione peroxidase is maximal, suggesting that
future research should investigate antioxidant pathways linking selenium to mood. This trial was registered with the Australian
New Zealand Clinical Trials Registry as ACTRN12613000773730. J Nutr 2015;145:5965.
Keywords:
Introduction
There is growing evidence for the role of micronutrients in
mental health, although the links between multivitamin-mineral
supplements, specific micronutrients, and mood remain inconclusive (1, 2). In a recent review, 4 of 8 trials demonstrated
decreases in depressed mood after supplementation with
1
Supported by a Health Research Council Emerging Researcher First Grant
(12/709) and a University of Otago Research Grant to TS Conner.
2
Author disclosures: TS Conner, AC Richardson, and JC Miller, no conflicts of
interest.
3
Supplemental Tables 13 are available from the Online Supporting Material
link in the online posting of the article and from the same link in the online table of
contents at http://jn.nutrition.org.
* To whom correspondence should be addressed. E-mail: tconner@psy.otago.
ac.nz.
59
Methods
Participants and inclusion/exclusion criteria. Participants were
recruited as part of the Daily Life Study, a large cross-sectional study
of the biological and genetic markers of well-being in a population of
young adults living in Dunedin, New Zealand. Participants were
recruited through flyers, an on-campus employment agency, or human
nutrition classes and reimbursed with a small payment, or through the
University of Otago Psychology Departments experimental participation program and reimbursed with course credit. The data were collected
in the fall months of March to May in 2011, 2012, and 2013 and in the
winter months of July and August 2013.
Participants were eligible to participate in the Daily Life Study if
they were at least part-time students at the University of Otago, were
aged #25 y, and had regular access to the Internet (n = 1061). We
excluded from analysis any study participants who reported current
antidepressant medication use (n = 36) or who failed to provide
sufficient data (no blood sample, n = 17; <1 wk of daily diaries, n = 30).
No other inclusion or exclusion criteria were applied due to the broad
focus of the Daily Life Study. Participants taking selenium supplements
60
Conner et al.
978
19.6 6 1.6
36.5
80.0
23.8 6 4.1
8.9 6 10.8
7.1
4.4 6 1.9
21.5
82 6 18
13.7 6 8.5
1.68 6 0.47
3.00 6 0.49
1
Values are means 6 SDs unless otherwise indicated. CES-D, Center for Epidemiological StudiesDepression; SES, socioeconomic status.
2
Smoking and SES data available for only a subset of participants: n = 379 for smoking
and n = 352 for SES.
3
SES rating of 4.4 corresponded to an average childhood household income of
$72,500 in New Zealand dollars.
4
Average mood scores ranged from 1 (not at all) to 5 (extremely). A midpoint score of
3 indicated moderately intense negative or positive mood.
Values are means 6 SDs unless otherwise indicated. *P , 0.05, **P , 0.01. B, unstandardized regression coefficient.
Only significant patterns are reported. Blinear and Bcurve reflect the linear and curvilinear patterns in the descriptive characteristics across selenium decile groups. The coefficients were obtained by entering selenium decile (110) and selenium
decile squared (1100) simultaneously to predict each characteristic. Nonsignificant curvilinear coefficients were dropped from the final models. Categorical variables were tested by using chi-square statistics.
3
Gender x2 (9, 978) = 31.11, P , 0.001; Ethnicity x2 (9, 978) = 93.5, P , 0.001.
4
Number of standard drinks of alcohol consumed per week.
5
Smoking and socioeconomic status data were available for only a subset of participants, which yielded 2842 participants per decile.
2
62 6 4
49 to ,67
19.5 6 1.5
19.6
93.8
25.6 6 6.3
7.4 6 9.4
12.5
4.3 6 1.8
73 6 1
72 to ,75
19.4 6 1.6
32.0
94.8
23.6 6 3.1
8.1 6 8.0
5.6
4.5 6 1.7
77 6 1
75 to ,78
19.4 6 1.6
30.6
89.8
23.4 6 3.4
9.5 6 11.6
10.0
5.0 6 1.7
79 6 1
78 to ,81
19.5 6 1.5
35.7
82.7
24.2 6 5.0
9.0 6 10.8
2.6
5.2 6 1.8
82 6 1
81 to ,84
19.4 6 1.6
34.3
77.8
23.5 6 3.7
9.7 6 12.1
12.5
4.3 6 1.8
89 6 1
87 to ,91
19.7 6 1.5
37.8
74.5
23.7 6 3.9
9.7 6 10.8
5.1
4.3 6 2.0
94 6 2
9197
20.0 6 1.7
42.9
68.4
23.3 6 3.5
9.5 6 11.9
4.8
4.1 6 2.2
110 6 38
98450
20.2 6 1.5
54.6
56.7
23.5 6 3.5
8.3 6 10.6
2.9
4.1 6 1.9
4 (n = 98)
3 (n = 97)
2 (n = 99)
1 (n = 97)
TABLE 2 Characteristics of the young adult participants (n = 978) categorized by decile of serum selenium concentration1
my life had been a failure and I felt that I could not shake off the blues
even with the help of my family or friends. Items were answered in
reference to the past week, and after reverse scoring of 4 items responses
were summed to give a total score. In community samples, a cutoff total
score of 16 is usually used to indicate significant levels of depressive
symptomatology (18).
Daily mood was measured each day for 13 d by using an 18-item
scale (19). The scale contained 9 adjectives assessing negative mood
(irritable, hostile, angry, nervous, tense, anxious, dejected, sad, unhappy)
and 9 adjectives assessing positive mood (excited, energetic, enthusiastic,
pleasant, happy, cheerful, content, calm, relaxed). Mood adjectives were
based on the affective circumplex and captured a range of high-,
medium-, and low-activation states (19). Participants were required to
rate each adjective on the basis of how they felt today on a 5-point
Likert scale: 1 (not at all), 2 (slightly), 3 (moderately), 4 (very much), 5
(extremely). Scores across the 9 adjectives were averaged each day to
obtain measures of daily negative mood (a = 0.780) and positive mood
(a = 0.820), which were averaged across days for analysis (a reliabilities
for nested data were computed by using recommended guidelines from
Nezlek; 20).
Serum selenium status. Serum selenium concentrations were measured by using an Agilent 7500ce quadrupole inductively coupled plasma
mass spectrometer in the Trace Element Centre, Chemistry Department,
University of Otago. National Institute of Standards and Technology
traceable calibration standards (High Purity Standards) and serum
samples were diluted 1:20 with a diluent containing 0.7 nmol/L
ammonia, 0.01 mmol/L EDTA, 0.07% Triton X-100, and butan-1-ol
1.5% vol:vol. The instrument was tuned according to the manufacturers
recommendations for a hydrogen reaction gas mode. Accuracy was
assessed by using an external certified reference material (UTAK
Laboratories) with a mean certified selenium value of 108 mg/L. Our
analysis gave a mean 6 SD of 112 6 3 mg/L, with a CV of 2.4% (n = 31).
In addition, multiple aliquots of pooled serum were analyzed during
each batch to determine the interassay CV, which was 1.2% (n = 82) at
72 mg/L.
Covariates. Demographic covariates were age (1725 y), gender (0 =
male, 1 = female), and self-reported ethnicity (0 = European ethnicity, 1 =
other ethnicity). Health covariates were BMI computed from measured
height and weight and weekly alcohol intake computed from a selfreported alcohol intake question included in the daily diary [number of
standard drinks of alcohol consumed the previous night, where
1 standard drink = 10 g of pure ethanol in a 330-mL can or bottle of
normal strength (4%) beer/cider, 1 very small (100 mL) glass of wine, or
1 small shot (30 mL) of liquor/spirits, straight or in a mixed drink]. Selfreported physical activity and cold symptoms were measured in the daily
diary but not included as covariates because neither was related to
selenium. The month of data collection and multivitamin use were tested
as covariates but dropped from analyses because they did not change the
results. For a subset of participants who completed the study in 2013,
smoking status (n = 379) and childhood SES (n = 352) were additionally
measured. Participants were defined as nonsmokers if they smoked
cigarettes once per month or less and as smokers if they smoked at least
once per week (nonsmokers = 0, smokers = 1). Childhood SES was
measured by self-reported household income while growing up (in New
Zealand dollars): 0 = <$15,000; 1 = $15,001$25,000; 2 = $25,001
$35,000; 3 = $35,001$50,000; 4 = $50,001$75,000; 5 = $75,001
$100,000; 6 = $100,001$150,000; and 7 = >$150,000.
Data analysis. Before analysis, serum selenium values were categorized
into deciles ranging from 1 to 10, from the lowest to highest 10% of
values. The use of deciles mitigated the influence of outliers and afforded
greater sensitivity than quintiles for detecting curvilinear patterns. An
ANCOVA general linear model was constructed to test the association
between serum selenium decile as the classification variable (predictor)
and depressive symptoms as the dependent variable, adjusting for age,
gender, ethnicity, BMI, and mean weekly alcohol intake as covariates.
This analysis yielded the adjusted least-squares mean CES-D (or mood)
scores for participants in each serum selenium decile. Assumptions of
Selenium and depressive symptoms in young adults
61
Conner et al.
Values are least-squares means (95% CIs) adjusted for age, gender, ethnicity, BMI, and alcohol intake unless otherwise indicated. ***P , 0.001. B, unstandardized regression coefficient.
Blinear and Bcurve reflect the linear and curvilinear effect of serum selenium decile on the predicted depressive symptoms or mood scores saved from ANCOVA. The coefficients were obtained by entering selenium decile (110) and selenium
decile squared (1100) simultaneously to predict the predicted depressive symptoms (Center for Epidemiological StudiesDepression) or mood scores. Least-squares means and predicted scores were nearly identical.
2
Depressive 15.9 (14.2, 17.6) 13.0 (11.3, 14.7) 15.1 (13.4, 16.8) 13.9 (12.3, 15.6) 13.3 (11.7, 15.0) 12.7 (11.0, 14.4) 12.5 (10.9, 14.2) 13.1 (11.4, 14.7) 13.0 (11.3, 14.7) 14.3 (12.6, 16.0) 21.15*** (21.29, 21.01)
0.087*** (0.075, 0.100)
symptoms
Negative
1.74 (1.64, 1.84) 1.67 (1.57, 1.76) 1.73 (1.64, 1.83) 1.68 (1.59, 1.78) 1.65 (1.55, 1.74) 1.69 (1.60, 1.78) 1.56 (1.46, 1.65) 1.67 (1.57, 1.76) 1.71 (1.62, 1.84) 1.75 (1.62, 1.81) 20.052*** (20.057, 20.047) 0.005*** (0.004, 0.005)
mood
Positive
2.93 (2.83, 3.03) 3.02 (2.92, 3.12) 2.95 (2.85, 3.05) 2.99 (2.89, 3.09) 3.07 (2.97, 3.16) 3.02 (2.92, 3.12) 2.97 (2.88, 3.07) 3.02 (2.92, 3.11) 3.01 (2.92, 3.11) 3.00 (2.90, 3.09)
0.034*** (0.023, 0.044)
20.003*** (20.004, 20.002)
mood
TABLE 3 Mean ANCOVA-adjusted depressive symptoms, negative mood, and positive mood for the young adult participants (n = 978) categorized by decile of serum selenium
concentration1
62
Results
Table 1 presents the participant characteristics and descriptive
statistics for the measured variables. Serum selenium concentrations ranged from 49 to 450 mg/L with the majority of cases
(99%) ranging from 49 to 158 mg/L. Depressive symptoms
ranged from 0.0 to 50.0, with 33.8% (n = 331) of our sample
reporting CES-D scores of $16.0, indicating significant levels of
depressive symptoms. Depressive symptoms correlated with
higher negative mood (r = 0.46, P < 0.001) and lower positive
mood (r = 20.41, P < 0.001). Negative mood and positive mood
were inversely correlated (r = 20.32, P < 0.001). Table 2
presents serum selenium concentrations and participant characteristics across the selenium deciles. Participants in the higher
selenium deciles were more likely to be older, male, nonEuropean, and of lower BMI. Participants in the middle
selenium deciles reported higher childhood SES than did
participants in the lower or higher selenium deciles. Table 3
presents the adjusted least-squares means of depressive symptoms, negative mood, and positive mood for each serum
selenium decile. There were significant linear and curvilinear
patterns across the serum selenium deciles in all 3 outcomes (all
P < 0.001).
Figure 1 shows the relations between selenium decile and
depressive symptoms (panel A), negative mood (panel B), and
positive mood (panel C) for the full sample, adjusted for the
primary covariates. For depressive symptoms, the pattern was a
reverse J-shaped curve, with the lowest depressive symptoms
among participants in selenium deciles 6 and 7 (82 6 1 and 85 6
1 mg/L serum selenium, respectively). Below and above this
range, depressive symptoms increased, particularly at the lowest
decile (decile 1; 62 6 4 mg/L serum selenium). For negative
mood, the pattern was a U-shaped curve with the lowest
negative mood among participants in selenium decile 7 (85 6
1 mg/L) and the highest negative mood among participants in
deciles 1 and 10 (62 6 4 and 110 6 38 mg/L, respectively).
However, the means for negative mood were all <2.00,
suggesting that negative mood did not increase above the
mild range. For positive mood, the pattern was an inverted
U-shaped curve with the highest positive mood among participants in selenium decile 5 (79 6 1 mg/L). Below and above this
range, positive mood decreased. This association between serum
selenium decile and adjusted positive mood was not due simply
to negative mood. Results from another ANCOVA entering
These relations between serum selenium decile and depressive symptoms, negative mood, and positive mood continued to
be significant when including smoking status and childhood SES
as additional covariates in the restricted sample of participants
(Supplemental Table 1). These relations were also significant
when including quadratic terms for both age and SES to control
for their curvilinear relations with serum selenium decile.
Hierarchical multiple regression analyses controlling for age,
gender, ethnicity, BMI, and alcohol intake confirmed these
significant negative linear and curvilinear relations between
serum selenium decile and depressive symptoms (linear B:
21.071; 95% CI: 21.898, 20.024; P = 0.011; curvilinear B:
0.082; 95% CI: 0.008, 0.155; P = 0.029) and negative mood
(linear B: 20.052; 95% CI: 20.098, 20.005; P = 0.029;
curvilinear B: 0.005; 95% CI: 0.001, 0.009; P = 0.029) but not
positive mood (linear B: 0.029; 95% CI: 20.19, 0.076; P = 0.24;
curvilinear B: 20.002; 95% CI: 20.006, 0.002; P = 0.31)
(Supplemental Table 2). Similar regression results were found
when controlling for age and SES as additional covariates
(Supplemental Table 3).
Discussion
63
Conner et al.
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