Association of Mood Disorders with Serum Zinc Concentrations in Adolescent Female Students
Among various factors influencing mood disorders, the impact of micronutrient deficiencies has attracted a great attention. Zinc deficiency is considered to play a crucial role in the onset and progression of mood disorders in different stages of life. The main objective of this study was to assess the correlation between serum zinc levels and mood disorders in high school female students. This cross-sectional study was conducted on a random sample of 100 representative high school female students. The participants completed 24-h food recall questionnaires to assess the daily zinc intakes. Serum zinc status was assessed using flame atomic absorption spectrometry, and zinc deficiency was defined accordingly. Mood disorders were estimated by calculating the sum of two test scores including Beck’s depression inventory (BDI) and hospital anxiety depression scale (HADS) tests. General linear model (GLM) and Pearson’s regression test were applied to show the correlation of serum zinc levels and mood disorder scores and the correlation between zinc serum levels and BDI scores, respectively. Dietary zinc intake was higher in subjects with normal zinc concentrations than that of zinc-deficient group (p = 0.001). Serum zinc levels were inversely correlated with BDI and HADS scores (p < 0.05). Each 10 μg/dL increment in serum zinc levels led to 0.3 and 0.01 decrease in depression and anxiety scores, respectively (p < 0.05). Serum zinc levels were inversely correlated with mood disorders including depression and anxiety in adolescent female students. Increasing serum levels of zinc in female students could improve their mood disorders.
KeywordsFemale Mood disorders Serum zinc levels Students Zinc
The burden of mental health disorders is considerably greater than what previously assumed . It is estimated that mood disorders are responsible for almost half of the total burden of diseases among young adults all over the world .
Depression is a common mood disorder which is associated with impaired function, significant disability, morbidity, and mortality . As a psychiatric disorder, depression is the cause of 50–70% of suicides . According to the report of the World Health Organization by 2020, depression will be the second most important cause of human disability . The lifetime risk for depression is 10 to 25% and 5 to 12% in women and men, respectively .
Among other mood disorders, anxiety is described as an emotional state that includes feeling apprehension, tension, and nervousness which is accompanied by physiological arousal . Anxiety disorders are the most prevalent psychiatric illnesses in the general community, present in 15–20% of all patients .
There is increasing body of evidence revealing the role of nutrition in depression and anxiety [8, 9]. Among nutritional factors, trace element deficiencies have been the subject of considerable interest. Biologically, zinc has three roles as follows: regulatory, catalytic, and construction. As an important trace element, zinc is essential for proper function of over 300 metalloenzymes in the body . Moreover, zinc plays an important role in the DNA replication, transcription, and protein synthesis, influencing cell division and differentiation . In addition, the human genes encode about 3000 zinc proteins. Furthermore, zinc acts as a signaling ion in the human brain . Considering the highest levels of zinc in areas of the brain known to be important in manifestation of depression and anxiety, including cerebral cortical regions, hippocampus, and lateral septum compared to the other parts of the central nervous system (CNS), low levels of zinc have been linked to mood disorders. The association of zinc with prevalence of neurologic and mood disorders has been considered for different age groups [12, 13, 14, 15]. Maes M. and colleagues reported a significant decrease in serum zinc concentration in patients with depression . Sawada, T. and colleagues evaluated the effect of 7-mg zinc supplementation for 10 weeks on mood states in young women and observed a significant reduction in anger and depression . Despite the growing evidence indicating the role of zinc in mood disorders, scarce studies have investigated the relationship between zinc status and prevalence of anxiety and depression. The higher risk of zinc deficiency has been observed among adolescents that might be due to their unhealthy food habits and poor bioavailability of zinc from plant-based diets . This study was, therefore, designed to evaluate the association between serum zinc concentration and mood states including depression and anxiety in female adolescent students.
Study protocol was approved by the Medical Ethics Committee at Jundishapur University of Medical Sciences and was registered under the number U-90276. The main researcher (KT) obtained written informed consent from all parents and the subjects assented to participate in our study. Furthermore, the subjects were allowed to refuse to participate and were free to leave the study by any reason. In addition, the subjects’ anonymity was reserved in all levels of the study from data gathering to manuscript publication.
Material and Methods
The data were collected from a random sample of high school girls (15–20 years) living in Izeh city, Khuzestan province, southwest of Iran. There was one vocational female high school in the city that was selected for this study (the other one was a high school boy). About 25% of the student population was randomly selected yielding 105 students. The first author (KT) performed the randomization from the list of all the students by means of a random number table. Five students were unable to follow the course due to unwillingness of their parents; totally, 100 students remained to finish the study. They were interviewed by the first author (KT), and their medical record sheets were evaluated by the high school health instructor. The study protocol was described to them, and all the parents gave the written consent and the subjects assented to participate. Inclusion criteria were being healthy student and willing to participate. Exclusion criteria consisted of being on medications for any chronic diseases such as mental/congenital or metabolic diseases; and any abnormalities in hematology, liver, renal, and thyroid function confirmed by screening laboratory reports. Those taking vitamin/mineral supplements were also excluded.
Participants’ History and Demographic Data
Basic characteristics of the female students based on their serum zinc status
Zinc deficient (n = 17)
Normal zinc status (n = 83)
17.92 ± 1.21
17.53 ± 1.03
158 ± 5.44
159 ± 4.91
55.9 ± 12.14
53.4 ± 10.61
22.38 ± 4.43
20.99 ± 4.11
Dietary intake (mg/day)
7.61 ± 1.19
9.88 ± 2.03
Serum levels (μg/dL)
62.23 ± 4.34
114.38 ± 27.40
14.9 ± 7.3
17.4 ± 6.5
10.6 ± 2.6
10.9 ± 3.4
1.4 ± 0.35
1.5 ± 0.4
483 ± 206
506 ± 218
Physical activity level (min/day)
- Less than 10
- 10 to 20
- More than 20
Sleeping patterns (hours/day)
- Less than 4
- 4 to 6
- 6 to 8
- More than 8
Monthly income of family
- Low (<300 USD)
- Usual (300–700 USD)
- High (>700 USD)
- 3–4 times/week
- Once a week
- 3–4 times/week
- Once a week
Socioeconomic status (SES) was assessed by parental education levels and family income status. The SES questions were adapted from a modified Ethiopia demographic and health survey 2005 report .
Dietary and Anthropometric Measurement
The participants completed 24-h food recall questionnaires to assess the daily zinc intakes. Height and weight were measured by a trained dietitian in the same and standard situations. Student’s weight was measured on a digital scale (Seca; Hamburg, Germany) and recorded to the nearest 100 g. The scale was calibrated before measurements using the calibration weights. The students wore light clothing, with no shoes and heavy outer wears (e.g., sweaters) before the measurements. Height was measured using a non-stretched Seca wall height scale (Seca 206, Seca GMBH & Co.; Hamburg, Germany) to the nearest 0.1 cm.
The subjects were asked to remove any hair ornaments, jewelry, buns, or braids from the top of the head. Also, the examiner checked that the subjects stand straight without shoes, and the “back of the head, shoulder blades, buttocks, and heels made contact with the backboard at time of measurement” .
A venous blood sample (5 mL) was collected from each participant in a sitting position after 8- to 10-h overnight fast (between 8:00 am and 10:00 am) done by an experienced laboratory technician. Supernatant serums were separated using 3000-rpm centrifuge for 10 min and were then stored at −80 C for further analyses. No hemolysis sample was observed in the specimens.
Serum zinc levels were measured using atomic absorption spectrometer (Chemtech, model CTA 3000; England) by setting wavelength 213.9 nm and slit width 0.7 nm. Serum zinc concentrations lower than 70 μg/dL were regarded as deficiency .
Mood Disorder Tests
A 21-item Beck’s depression inventory (BDI) questionnaire was applied to assess depression symptoms and severity in the students. Scores below 15, 15–19, 20–29, and 30–63 were regarded as normal, mild, moderate, and severe depression, respectively . This instrument is a self-scoring tool for reporting severity of the symptoms of depression. Reliability and validity of the Persian version of 21-item BDI was acceptable with satisfactory test-retest reliability (r = 0.74) and a high internal consistency with Cronbach’s alpha = 0.87 .
The hospital anxiety and depression scale (HADS) was applied to measure both anxiety and depression in out-patient populations. Each sub-scale comprised seven items which were rated on a four-point scale and scored from 0 to 3 with total scores, therefore, ranging from 0 to 21 for each sub-scale. Scores between 0 and 7 represent “no case,” 8 to 10 indicate “possible case,” and 11 to 21 suggest a “probable case of anxiety/depression” . This instrument had been validated in Persian society, before. Its internal consistency was acceptable with Cronbach’s alpha coefficient of 0.78 for the HADS anxiety sub-scale and 0.86 for the HADS depression sub-scale. Also, discriminate validity of this instrument for both anxiety and depression sub-scales has been confirmed by diagnosing between sub-groups of patients differing in clinical status as defined by their disease stage . Mood disorder score was calculated as the sum of the two disorders mentioned above. The abovementioned tests were performed in a comfortable condition while the subjects were seating on a comfortable chair in a private room without any tensions.
Data were exported to SPSS® (version 18) and were analyzed using selected descriptive and analytical statistical measures. Pearson’s regression test was used to show the correlation between serum zinc levels and depression/anxiety. General linear model (GLM) was used to determine the correlation between serum zinc levels and mood disorder scores.
A total sample of 100 participants was recruited to the study. Table 1 indicates the baseline characteristics of the participants. Accordingly, the mean scores for depression and anxiety tests were 18.2 ± 10.42 and 9.7 ± 4.3, respectively. Of all, 46% were non-depressed, 11% were affected with mild depression, 27% with moderate depression, and 16% with severe depression; 21% were affected with mild anxiety, 30% with moderate anxiety, and 15% with severe anxiety, and 34% were not affected with anxiety.
Results on meat consumption in Table 1 indicate that there were no significant differences between the groups regarding the consumption of two types of meats as the main dietary zinc sources in local nutritional pattern.
Correlation between serum zinc concentrations and mood disorder scores of the female students
%95 confidence interval
Decrease in scores
Decrease in scores
Decrease in scores
To our best knowledge, this is the first study in which the relation of serum zinc levels with depression and anxiety in young girls is investigated. A significant inverse correlation between serum zinc concentrations and depression and anxiety scores was observed. Each 10-μg/dL increase in serum zinc levels led to 0.1 and 0.03 mark decreases in depression and anxiety scores, respectively (Table 2).
Among the proposed mechanisms for the role of zinc in attenuating mood disorders, modulating n-methyl diaspartate (NMDA) function, inhibiting chronic over production of cortisol, and neuroproducing role of zinc in the brain are considered crucial [25, 26, 27].
The finding of our study was in agreement with other studies conducted by Islam et al., Yary et al., and Jacka et al. on subjects with depression [28, 29, 30]. In a cross-sectional study conducted by Amani et al., significant lower levels of serum zinc were observed in depressed female students in comparison with healthy matched subjects. Moreover, in their study, inverse correlation was seen between both dietary zinc intake and serum zinc levels with depression scores . In another study on pregnant women, it was shown that lower zinc intake, higher stress, and social disadvantage were associated with the occurrence of depressive symptoms, which were, in turn, attenuated by higher zinc intake . Moreover, Siwek et al. found that treatment-resistant depressed patients exhibit much lower-serum zinc concentrations than their non-treatment-resistant depressed counterparts . The latter finding might provide more evidence in favor of zinc deficiency on mood disorders in developing countries, where mild to moderate zinc deficiency is common . Ranjbar E. and colleagues conducted a 12-week double-blind clinical trial to investigate the effects of 25-mg zinc augmentation to selective serotonin reuptake inhibitors (SSRIs), in the treatment of depression. The results of this study indicate that zinc supplementation together with SSRI antidepressant medication significantly improved major depressive disorders . Ranjbar E. et al. proposed that zinc supplementation may reduce the inflammatory cytokines and elevate the brain-derived neurotrophic factor (BDNF) and, accordingly, plays a role in reducing the severity of major depression .
On the other hand, limited studies have shown no relation between zinc status and mood disorders [13, 37]. Considering the limitations indicated in the previous studies [28, 29, 37, 38], and in order to modulate the impact of confounding factors such as socioeconomic status (SES), a complete information of the SES were obtained from our participants and then were adjusted in data analysis.
Furthermore, some concerns exist about hidden zinc deficiency  which may have minimal effect on our results since false negatives make our results more conservative. Also, here, zinc deficiency pathology in adolescent girls is worthy of attention; Yokoi found simple food frequency and menorrhagia predicted low-zinc status measure . Zinc absorption and hence serum zinc concentration can be predicted from dietary zinc intake. Bioavailability of dietary zinc increases in zinc-deficient subjects. In fact, they absorb dietary zinc more efficiently from low-zinc diets at least for more than a few weeks . Paying attention to the zinc kinetics and its bioavailability and adaptation is critical for interpretation of the results of zinc deficiency studies. Zinc bioavailability depends on the amount of zinc stored in the body, dietary zinc content, and inhibitors of zinc absorption. Zinc from animal sources absorbs more efficiently; phytate in the plant sources, such as whole grain and legumes, binds tightly to zinc in the gastrointestinal tract and decreases zinc bioavailability. Since phytate is the main inhibitor of zinc absorption, dietary phytate:zinc molar ratio is used to estimate the efficiency of zinc absorption . Furthermore, interaction with other cations in the intestinal lumen may also affect the bioavailability of zinc. As mentioned before, the main objective of this study was to assess the correlation between serum zinc levels and mood disorders in high school female students. Hence, we did not intend to assess the bioavailability of dietary zinc. However, to show that zinc bioavailability has not affected our results, we compared the mean intake of common inhibitors of zinc absorption (including fiber, iron, calcium, and copper; Table 1) and observed no significant difference between zinc-deficient and normal-serum zinc groups.
As a strong point of our study, it should be mentioned that each test was applied separately on a particular day. Moreover, the tests were performed in comfortable conditions. Besides, the surrounding environment was totally prepared while administering the mood tests. As the limitation of this study, we can name the importance of zinc absorption inhibitors such as phytates that should be taken into account in local dietary pattern.
Considering the suggested mechanisms for the potent role of zinc in the brain and maintaining its function, this study could be regarded as a preliminary evidence for the key role of zinc status in mood disorders in young girls at pilot scale . Based on this study, we would suggest that further studies are needed to focus on the bioavailability of dietary zinc in the region. At this point, controlled randomized trials are required in order to precisely investigate the effects of zinc status on mood disorders in different ages and physiological conditions. Longitudinal studies that include performance in school would be useful as well.
We wish to thank all the participants and their parents and also the colleagues at the high school who kindly co-operated with us.
Compliance with Ethical Standards
This study was a part of Ms. Kobra Tahmasebi’s MSc thesis, and the laboratory costs were covered by a grant of Vice-chancellor for Research at the Jundishapur University of Medical Sciences.
Conflict of Interest
The authors declare that they have no conflict of interest.
“All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from parents of all subjects and assent was obtained from all individual participants included in the study.”
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