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 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 35  |  Issue : 1  |  Page : 65-70

A study on 25-OH cholecalciferol levels in children and adolescents with major depressive disorder


1 Department of Psychiatry, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Clinical Pathology Department, Zagazig University Hospitals, Zagazig, Egypt

Date of Submission20-Apr-2013
Date of Acceptance08-Aug-2013
Date of Web Publication18-Feb-2014

Correspondence Address:
Saber Abdel Azim Mohamed
Department of Psychiatry, Faculty of Medicine, Zagazig University, Zagazig
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-1105.127286

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  Abstract 

Background
Low vitamin D levels are associated with schizophrenia, depression, and seasonal affective disorder in adults. The relationship between vitamin D and depression in pediatric population is little investigated.
Aim of the study
The aim of the study was to determine the association between depression severity and serum levels of 25-OH cholecalciferol in children and adolescents.
Patients and methods
A total of 82 depressed children and adolescents and 21 age-matched and sex-matched healthy controls were enrolled in the study. All participants were subjected to sociodemographic variables, medical and psychiatric examination, psychometric evaluation by the semistructured clinical interview and Hamilton Depression Rating Scale, routine laboratory investigations, and serum 25-OH cholecalciferol levels measurement.
Results
There was no significant difference between the groups with respect to age, sex distribution, BMI, family income, and residency. Children of joint paternal family type and with positive psychiatric family history have statistically significant increase in the severity of depression compared with those of other family types and with negative psychiatric family history. Vitamin D levels and severity of depression were inversely correlated; the more severe the depression was, the lower was the level of vitamin D.
Conclusion
25-OH cholecalciferol deficiency is more prevalent in depressed children and adolescent patients than in normal children. Vitamin D supplementation in depressed children might be further investigated in the future.

Keywords: 25-OH cholecalciferol, adolescent, children, depression, vitamin D


How to cite this article:
Mohamed SA, Khalil DM, El Melegy AM, Raya YM. A study on 25-OH cholecalciferol levels in children and adolescents with major depressive disorder. Egypt J Psychiatr 2014;35:65-70

How to cite this URL:
Mohamed SA, Khalil DM, El Melegy AM, Raya YM. A study on 25-OH cholecalciferol levels in children and adolescents with major depressive disorder. Egypt J Psychiatr [serial online] 2014 [cited 2021 Jun 19];35:65-70. Available from: http://new.ejpsy.eg.net/text.asp?2014/35/1/65/127286


  Introduction Top


Since the dawn of human history, the sun, springtime, warm weather, and open, lightly shaded landscapes have been associated with happiness and positive feelings, in the literature, visual art, and religion (Humble, 2010). Vitamin D deficiency has been documented to be associated with significant medical and psychological consequences. Low vitamin D levels are associated with schizophrenia, depression, and seasonal affective disorder in adults. The relationship between vitamin D and depression in pediatric population is little investigated. Vitamin D deficiency might be caused by lack of sunlight exposure, insufficient dietary intake, dark skin, and diets poor in dairy products.

The importance of vitamin D to the central nervous system in both healthy and psychiatric populations is less well appreciated and is vastly understudied compared with its known impact on bone health. Vitamin D receptors are present throughout the brain, and vitamin D deficiency is associated with negative central nervous system effects in animal studies (McCann and Ames, 2008).

However, recent literature studying vitamin D deficiency in depression have had conflicting results. Furthermore, relationship between vitamin D in children and adolescent depression is more unclear and less studied. In a large cohort study (Milaneschi et al., 2013), low levels of 25-hydroxyvitamin D [25(OH)D] were associated with the presence and severity of depressive disorder, suggesting that hypovitaminosis D may represent an underlying biological vulnerability for depression.

Vitamin D concentrations have been shown to be low in patients suffering from mood disorders and have been associated with cognitive function (Wilkins et al., 2006; Przybelski and Binkley, 2007). Leading theories as to how vitamin D may play a role in depression include promoting genes coding for brain derived neurotrophic factor (BDNF) (Naveilhan et al., 1996) leading to the development of dopaminergic neurons and promoting genes coding for tyrosine hydroxylase (Puchacz et al., 1996), which catalyzes the production of catecholamines.

The Third National Health and Nutrition Examination Survey, which used a sample of 7970 noninstitutionalized US residents aged 15-39, demonstrated that individuals with serum vitamin D of 50 nmol/l or less are at a significantly higher risk of developing depression than those with vitamin D of at least 75 nmol/l (Ganji et al., 2010). A study on 1282 adults aged 65-95 in the Netherlands found that 25(OH)D levels were 14% lower in depressed patients compared with controls (Hoogendijk et al., 2008). However, a large epidemiologic study in China did not detect a relationship between vitamin D and depression in 3262 men and women aged 50-70 (Pan et al., 2009). After researchers adjusted for geography, BMI, physical activity, and smoking, 25(OH)D levels did not correlate significantly with the presence or severity of depression.

In a case series (Högberg et al., 2012), after 48 vitamin D-deficient depressed adolescents were given vitamin D 3 over 3 months, there was a significant improvement in well-being, depressive symptoms, irritability, and fatigue.

Other small, cross-sectional studies have examined the associations between vitamin D status and depression with divergent results, which may reflect the differences in population and methodology (Högberg et al., 2012).

Kjζrgaard et al. (2012) systematically examined vitamin D levels in a case-control study followed by a randomized controlled trial on vitamin D supplementation. In the case-control phase, participants with low 25(OH)D levels at baseline were significantly more depressed than participants with high 25(OH)D levels. Participants with low 25(OH)D levels were randomized to placebo or 40 000 IU vitamin D 3 per week for 6 months. Low levels of vitamin D were strongly associated with depressive symptoms, but vitamin D supplementation did not have a significant effect on the depressive symptom scores.


  Aim of the study Top


This study was conducted to determine the association between severity of major depressive disorder and vitamin D serum levels in children and adolescents.


  Patients and methods Top


Patients

Eighty-two depressed children and adolescent patients and 21 age-matched and sex-matched healthy controls were recruited for this cross-sectional study. Depressed patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revised (DSM-IV-TR) diagnostic criteria (APA, 2000). The study was conducted at child psychiatry outpatient clinic in Al Amal Mental Hospital, Riyadh, Kingdom of Saudi Arabia. Written informed consent was obtained from caregivers after approval from the ethical committee. Patients aged 7-18 years old and fulfilling the DSM-IV-TR diagnostic criteria for major depression were included. However, those with known metabolic or endocrinal disorder, malnutrition, hematological liver or kidney disease or other chronic medical disease, neurological disorder, psychotic disorder, alcohol or illicit substance abuse disorder, developmental disorder, learning disability disorder, or other axis I psychiatric diagnoses were excluded from participation in the study.

Materials and methods

Selected participants were subjected to full medical examination including BMI and thorough psychiatric evaluation. They were further subjected to psychometric evaluation and laboratory investigations. BMI was calculated as body weight (kg) divided by the square of height (m 2 ). The controls were selected from staff relatives.

Psychometric measures

Semistructured clinical interview was conducted. It is a standardized form derived from clinical case assessment sheet at Al Amal Mental Hospital, containing sociodemographic variables including age, sex, education, family income and type, residence, number of siblings, and psychiatric family history.

Family income was determined according to 2011 gross national income per capita, calculated using the World Bank  Atlas More Details method. The groups were classified into low income $1025 or less; middle income $1026-$12 475; and high income $12 476 or more (http://kff.org/global-indicator/country-income-classification/).

Family type was classified into three types: (a) joint family (http://dictionary.reference.com/browse/187580), a type of extended family composed of parents, their children, and the children's spouses and offspring in one household; (b) joint paternal as above but parents are related to the husband; (c) joint maternal as above but parents are related to the wife; and (d) nuclear family (http://dictionary.reference.com/browse/194550), a social unit composed of two parents and one or more children.

Hamilton Depression Rating Scale (HDRS) (Hamilton, 1960) is a widely used and reliable scale for depression severity. The score range for mild depression in this scale is 11-13, moderate depression is 14-18, and severe depression is 19-21. However, item number 14 was excluded at those young ages, as it is concerned with sexual dysfunction and libido.

Laboratory investigations including complete blood count, serum electrolytes, liver function tests, kidney function tests, chest radiography, and 25-OH cholecalciferol levels were performed by Elecsys vitamin D testing method (Hollis and Horst, 2007).

The Elecsys vitamin D assay is an electrochemiluminescence competitive protein binding assay that uses vitamin D binding protein instead of monoclonal antibodies for detection of 25(OH)D.

  1. The total duration of the assay is 27 min. The sample is treated with pretreatment reagent during the first incubation period. This releases any vitamin D from the endogenous vitamin D binding protein present in the patient's sample.
  2. In the next incubation, vitamin D binding protein labeled with ruthenium is added and a complex is formed between 25(OH)D and ruthenylated vitamin D binding protein.
  3. In the third and final incubation, streptavidin-coated microparticles are added along with 25(OH)D labeled with biotin.
  4. Any unbound ruthenium-labeled vitamin D binding proteins become occupied with biotin-labeled 25(OH)D. The complex consisting of the ruthenylated vitamin D binding protein and the biotinylated 25(OH)D becomes bound to the solid phase through interaction of the biotin and streptavidin.
  5. The reaction mixture is aspirated into the measuring cell where the electrochemiluminescence emission is detected. Results are determined using a calibration curve that is generated specifically on each instrument by a two-point calibration provided with the reagent bar code.


Data management and statistical analysis

The data have been coded and entered on an IBM compatible personal computer using the statistical package SPSS version 16. The data were summarized using mean and SD for continuous type, whereas percentage was used for the qualitative type. The differences between the groups were tested using the Student t-test. The χ2 -test was used for qualitative data. The correlation between the two continuous groups was assessed using Pearson's correlation test. The level of significance for all above-mentioned tests was at P-value less than 0.05 (Dawson-Saunders and Trapp, 1990).


  Results Top


General characteristics of the sample

A total of 82 depressed and 21 normal healthy control children and adolescents participated in our study. We found no statistically significant difference in age distribution between the four studied groups: controls 14.86 ± 4.55 years with range 11-18, mild 13.33 ± 3.09 years with range 10-18, moderate 13.26 ± 3.54 years with range 7-18, and severe 11.96 ± 4.96 years with range 6-18 [Table 1]. We found no significant sex distribution using the χ2 -test (controls 43% male individuals and 57% female individuals, mild depressed 52% male individuals and 48% female individuals, moderate depressed 53% male individuals and 47% female individuals, and severely depressed patients 24% male individuals and 76% female individuals) [Table 2]. We found no statistically significant differences with respect to BMI in all study groups (control 20.29 ± 4.35, mild depressed 23.04 ± 4.97, moderate depressed 22.76 ± 6.26, and the severely depressed group 21.7 ± 7.5) [Table 3].
Table 1: Age distribution among the study groups

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Table 2: Sex distribution among the study groups

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Table 3: BMI in the study groups

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Sociodemographic variables

We found a high statistically significant difference between the severity of depression, family type, family history, and smoking in which the moderate and severe degree of depression were significantly higher among joint paternal family and among those with the presence of family history of psychiatric illness (P < 0.05); in addition, mild and moderate depression was significantly higher among smokers as compared with controls. Meanwhile, there was no statistically significant difference between the severity of depression, family income, residence, and BMI (P > 0.05) [Table 4].
Table 4: Comparison between the four study groups with respect to family type, family income, residency, family history, and smoking

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Hamilton depression rating scale and vitamin D

We found that there was high statistically significant difference in the severity of depression and both HDRS and vitamin D; the higher the level of HDRS, the more severe the degree of depression and conversely, the lower the level of vitamin D, the more severe the degree of depression (P < 0.05) [Table 5]. With respect to the correlation between HDRS and vitamin D (pg/ml), studied patient showed negative correlation between vitamin D severity and HDRS, where vitamin D levels tend to be lower with an increase in the severity of depression [Figure 1].
Figure 1:

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Table 5: Comparison of the study groups with respect to hamilton depression rating scale and vitamin D

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{Figure 1}

The following parameters were analyzed:

  1. Age distribution in the four groups.
  2. Sex distribution.
  3. BMI.
  4. Sociodemographic variables in all groups.
  5. HDRS and vitamin D comparisons in the study groups.
  6. Correlation between vitamin D levels and HDRS.



  Discussion Top


The major finding in our study was the low serum levels of vitamin D in more severely depressed children and adolescents and its inverse relationship with the degree of depression severity. We also found high prevalence of depression among both participants with positive family history of psychiatric illness and of the joint paternal family type compared with those with negative family history and of other family types, respectively.

Basic and preclinical animal research provides clues as to how vitamin D deficiency may increase the risk for depression. Several mechanisms of action have been proposed to explain the association between vitamin D and depression. The role of calcitriol or 1, 25-dihydroxy cholecalciferol, the bioactive form of vitamin D, in the brain tissue has been confirmed by the presence of vitamin D receptors and hydroxylases in various brain regions (Pruefer et al., 1999; Eyles et al., 2005). One area where vitamin D receptors and hydroxylases have been found is the amygdala, which is the center of the limbic system, where behavior and emotions are regulated (Walbert et al., 2001). Vitamin D has been reported to exert a neuroprotective function through several mechanisms. Calcitriol regulates calcium concentrations intracellularly and extracellularly in the neurons, consequently reducing the toxicity caused by excess calcium (Shinpo et al., 2000; Garcion et al., 2002; Kalueff et al., 2004).

Ganji et al. (2010) found higher prevalence of vitamin D deficiency in women, non-Hispanic blacks, people with higher BMI, people with lower income, people living in urban areas, and people living in the south compared with their counterparts.

Excitingly, we found that low levels of vitamin D were associated with an increase in the severity of depression, which is in agreement with Jorde et al. (2008), Lee et al. (2009), and Ganji et al. (2010). They found that the prevalence of depression increased as serum 25-OH cholecalciferol decreased. However, Nanri et al. and Zhao et al. in cross-sectional separate studies found no association between vitamin D deficiency and the presence of major depression, minor depression, and moderate to severe depression. This contradiction between our results and their might be attributed to the methodological and sampling differences, for example the high age of participants in both studies in comparison with our sample age range in addition to the sampling time.

However, we found no statistically significant association between BMI and the severity of depression. It is in contrast with the study by Ganji et al. (2010) who found low levels of vitamin D in people with higher BMI. However, they conducted their work on a large US population sample and young adults. It is well known that vitamin D levels decrease with aging, which might explain the difference between our studies.

In addition, we found a significant increase in the depression severity in those children and young adolescents who have positive family history of depression. This finding was in agreement with the well-known clinical fact that there is an increased prevalence of depression in families with positive history of psychiatric illness.

Finally, we found an inverse correlation between vitamin D serum levels and the severity of depression by HDRS. However, it is not known which is cause and which is effect.

Limitations

Our study was limited by the relatively small sample size, the cross-sectional design, outpatient sampling basis, absence of seasonal vitamin D measurements, absence of study on sun exposure of participants, absence of study on the skin color of patients, and lack of parathyroid hormone levels measurement.


  Conclusion and summary Top


Vitamin D deficiency is more prevalent in depressed children and adolescent patients than in normal controls. Our study might be considered a leading one in measuring 25-OH cholecalciferol in depressed children and adolescents. It confirms the relationship between vitamin D deficiency and depression in children and in adult population. However, it is still unknown which is cause and which is effect. Vitamin D supplementation in depressed children might be raised up and further investigated in future studies.

Recommendation

More attention must be paid to the nutritional status of children and adolescents. Vitamin D supplementation should be further investigated as a nutritional supplement for depressed children and adolescents.[26]


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.APA. Diagnostic and statistical manual of mental disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association; 2000.  Back to cited text no. 1
    
2.B Dawson-Saunders, RG Trapp. Basic and clinical biostatistics. : Appleton & Lange; 1990.  Back to cited text no. 2
    
3.Eyles D, Smith S, Kinobe R, Hewison M, McGrath J (2005). Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29:21-30.  Back to cited text no. 3
    
4.Ganji V, Milone C, Cody MM (2010). Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey. Int Arch Med 3:29.  Back to cited text no. 4
    
5.Garcion E, Wion-Barbot N, Montero-Menei C, Berger F, Wion D (2002). New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 13:100-105.  Back to cited text no. 5
    
6.Hamilton A. A rating scale for depression (1960). J Neurol Neurosurg Psychiatry 23:56-62.  Back to cited text no. 6
    
7.Högberg G, Gustafsson SA, Hällström T (2012). Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation. Acta Paediatr 101:779-783.  Back to cited text no. 7
    
8.Hollis BW, Horst RI (2007). The assessment of circulating 25(OH)D and 1,25(OH)2D: where are we and where are we going. J Steroid Biochem Mol Biol 103:473-476.  Back to cited text no. 8
    
9.Hoogendijk WJ, Lips P, Dik MG (2008). Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry 65:508-512.  Back to cited text no. 9
    
10.Humble M (2010). Vitamin D, light and mental health. J Photochem Photobiol B 101:142-149.  Back to cited text no. 10
    
11.Jorde R, Sneve M, [Figureenschau Y (2008). Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med 264:599-609.  Back to cited text no. 11
    
12.Kalueff A, Eremin K, Tuohimaa P (2004). Mechanisms of neuroprotective action of vitamin D 3 . Biochemistry (Mosc) 69:738-741.  Back to cited text no. 12
    
13.Kjærgaard M, Waterloo K, Wang CE (2012). Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. Br J Psychiatry 201:360-368.  Back to cited text no. 13
    
14.Lee DM, Tajar A, Ulubaev A (2009). Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men. J Neurol Neurosurg Psychiatry 80:722-729.  Back to cited text no. 14
    
15.McCann J, Ames B (2008). Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J 22:982-1001.  Back to cited text no. 15
    
16.Milaneschi Y, Hoogendijk W, Lips P, Heijboer AC, Schoevers R, van Hemert AM, et al (2013). The association between low vitamin D and depressive disorders. Mol Psychiatr, 9 April 2013; doi:10.1038/mp.2013.36.  Back to cited text no. 16
    
17.Nanri A, Mizoue T, Matsushita Y, et al. (2009). Association between 25-hydroxyvitamin D and depressive symptoms in Japanese: analyses by survey season. European Journal of Clinical Nutrition 63:1444-1447.  Back to cited text no. 17
    
18.Naveilhan P, Neveu I, Wion D (1996). 1,25-dihydroxyvitamin D 3 , an inducer of glial cell line derived neurotrophic factor. Neuroreport 2171-2175.  Back to cited text no. 18
    
19.Pan A, Lu L, Franco OH (2009). Association between depressive symptoms and 25-hydroxyvitamin D in middle aged and elderly Chinese. J Affect Disord 118:240-243.  Back to cited text no. 19
    
20.Pruefer K, Veenstra T, Jirikowski G, Kumar R (1999). Distribution of 1,25 dihydroxyvitamin D 3 receptor immunoreactivity in the rat brain and spinal cord. J Chem Neuroanat 16:135-145.  Back to cited text no. 20
    
21.Przybelski R, Binkley N (2007). Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys 460:202-205.  Back to cited text no. 21
    
22.Puchacz E, Stumpf W, Stachowiak E (1996). Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. Mol Brain Res 36:193-196.  Back to cited text no. 22
    
23.Shinpo K, Kikuchi S, Sasaki H, Moriwaka F, Tashiro K (2000). Effect of 1,25 dihydroxyvitamin D 3 on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by buthionine sulfoximine and 1-methyl-4-phenylpyridine. J Neurosci Res 62:374-382.  Back to cited text no. 23
    
24.Walbert T, Jirikowski GF, Prüefer K (2001). Distribution of 1,25 dihydroxyvitamin D 3 receptor immunoreactivity in the limbic system of the rat. Horm Metab Res 33:525-531.  Back to cited text no. 24
    
25.Wilkins C, Sheline Y, Roe C, Birge S, Morris J (2006). Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry 14:1032-1040.  Back to cited text no. 25
    
26.Zhao G, Ford E, Li C, et al. (2010). No associations between serum concentrations of 25-hydroxyvitamin D and parathyroid hormone and depression among US adults. British Journal of Nutrition 104:1696-1702.  Back to cited text no. 26
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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