Skip to main content
Egyptian Liver Journal
Download PDF

Association between vitamin D status and depression in children with chronic liver disease

Egyptian Liver Journal volume 10, Article number: 34 (2020) Cite this article

Abstract

Background

Deficiency of vitamin D and depression are commonly occurring in patients with chronic liver diseases. This study aimed to determine the association between 25-OH-vitamin D status and depressive symptoms among children with chronic liver diseases. Eighty children were enrolled and divided into 2 groups: the patients’ group (60 children with chronic hepatitis) and the control group (20 healthy children). All children have been analyzed for their clinical, biochemical features, histological profile, serum 25-OH-vitamin D levels, and assessment of childhood depression using Arabic form based on Kovacs Children’s Depression Inventory.

Results

Serum level of 25(OH) D was significantly lower in the hepatic group than the control group [17 (5–52) ng/ml, 45 (13–95) ng/ml, p = <0001 respectively]. Depression score was significantly higher in the hepatic group as 30% of the control group had mild depression, while 36.7% of the hepatic group had mild depression, 16.7% had moderate depression, and 10% had severe depression. There was a statistically significant difference between children with depressive symptoms and non-depressive symptoms as regards the level of serum vitamin D as it was lower in children with depressive symptoms [median (range) 17 (5–40) ng/ml, 27.5 (8–52) ng/ml, p = 0.04 respectively]. There were statistically significant differences between the serum level of 25(OH) D and depression as it decreases with increasing severity of depression.

Conclusion

Children with chronic liver disease who had depressive symptoms showed significantly lower levels of vitamin D when compared with those without depressive symptoms; also, vitamin D had an inverse correlation with depression scores in these children.

Background

Chronic liver disease (CLD) is a progressive liver parenchyma destruction and regeneration which leading to fibrosis and cirrhosis (normally lasts 6 months). CLD’s etiological agents include hepatotropic viruses (HCV and HBV), fatty liver, and autoimmune hepatitis [1].

Depression, also known as major depressive disorder (MDD), major depressive episode (MDE), or clinical depression, is a mental disorder marked by pervasive and persistent low mood, followed by low self-esteem and loss of interest or enjoyment in usually pleasurable activities. CLD was long known and associated with depression [2,3,4].

Liver diseases may interfere with the development of the active vitamin D metabolites leading to abnormal calcium and bone metabolism [5, 6]. Vitamin D also had several other roles, including cell growth and control of the neuromuscular and immune system. Vitamin D deficiency is highly prevalent globally and is believed to be associated with an increased risk of major depressive disorder and anxiety disorders [7]. So this work aimed to investigate the association between vitamin D status and depressive symptoms among children with CLD.

Subject and methods

This case-controlled study was conducted on children diagnosed with CLD who attending the outpatient hepatology clinic after obtaining informed written consent from each parent of enrolled children in the period from October 2018 to July 2019 and apparently healthy children of matched age and sex acted as the control group. Children with comorbidity like renal diseases, heart diseases or parathyroid disease, prior parathyroid surgery, concurrent anticonvulsant treatment metabolized by cytochrome P450 activity, psychiatric disorders (psychosis or dementia), hepatic encephalopathy, and liver transplantation were excluded from this study, and the number of each category of the excluded patients was not recorded. The study was approved by Ethical Scientific Committee according to guidelines of the Helsinki Declaration [8].

❖ All the following were collected based on medical records and anamnesis: sociodemographic, clinical examination, abdominal ultrasonography, result of hepatic needle biopsy, laboratory parameters: hematological (complete blood picture (CBC), biochemical (liver function tests: [aspartate aminotransferase (AST), alanine aminotransferase (ALT)), alkaline phosphatase(ALP), gamma-glutamyl transpeptidase(GGT), total and direct bilirubin, serum protein and albumin] and serum creatinine) autoantibodies (anti-nuclear antibodies (ANA), smooth muscle antibodies (ASMA), liver-kidney microsome antibodies (LKM-1) and anti-mitochondrial antibodies(AMA)), and viral hepatitis profile.

❖ The severity of liver disease was quantified using Child-Pugh score [9], model for end-stage liver disease (MELD) score [10] for teens older than 12 years of age, and pediatric-related end-stage liver disease (PELD) score [11] for participants younger than 12 years of age.

❖ All the participants were evaluated for depression level based on Children’s Depression Inventory (CDI), a commonly used scale that tests depression symptoms in children and adolescents ages 7 to 17 years within the last 2 weeks [12] with the use of Arabic-translated form [13]. It measures negative mood (irrational thinking about people or events which means focusing on the negative and not seeing the positive in life), negative self-esteem (lack of confidence and feeling badly about oneself), anhedonia (loss of the capacity to experience pleasure), ineffectiveness (low capability of producing the desired result or the inability to produce desired output), and indecisiveness (not decisive or conclusive). The scale includes 27 items; each item consists of three choices of answers and the patient should choose one. Those 3 choices represent 3 degrees of severity of symptoms. According to the severity, the degree ranges from 0 to 2 as follows: no symptom, 0; mild to moderate, 1; and severe symptoms, 2. The score for both male and female ranging from 0 to 9 was considered normal, while mild depression in males was considered at 9–14 and in females at score 9–16, moderate depression in males at 15–18 and in females at 17–22, and severe depression in males at score > 18 and in females at score > 22. The questionnaire was administered by the same interviewer.

❖ Laboratory investigations: 3-ml venous blood was drawn by aseptic venipuncture using a disposable sterile syringe. Blood was used for the assessment of serum levels of 25-hydroxyvitamin D by enzyme-linked immunosorbent assay (ELISA). Quantitative measurement of bioactive Vit D was carried out using sensitive competitive ELISA kits supplied from WKEA Med Supplies Corporation, China. The normal level of vitamin D is defined as a 25-OH Vit D concentration greater than 20 ng/ml (> 50 nmol/L). Vitamin D insufficiency is defined as a 25-OH-Vit D concentration of 12–20 ng/ml (30–50 nmol/L). Vitamin D deficiency is defined as a 25-OH-Vit D level less than 12 ng/ml (< 30 nmol/L) [14] for all the participants.

Statistical analysis

Data were tabulated, coded, and then analyzed using the computer program SPSS (statistical package for social science) version 16. Quantitative data were presented as mean ± SD. The χ2 test and Fisher exact test were used to compare proportions as appropriate. The Student’s t test and the Mann–Whitney (Z) test were used to test differences between the two groups regarding parametric and non-parametric data, respectively. Spearman’s correlation coefficient was used to test the correlation between variables. For all analyses, the level of significance was set at p < 0.05.

Results

Study population characteristics

The mean age of the studied 60 children suffering from chronic liver disease of different etiologies is 12 ± 3 years; they were 33 (55%) male and 27 (45%) female. Twenty-one (35%) of them had positive consanguinity, while the 20 control children were 10 females (50%) and 10 males (50%) with mean age 12 ± 4 years with 4 (20%) of them had positive consanguinity with no statistically significant difference between both groups as regards age, gender, and consanguinity. Regarding diagnosis of chronic liver disease group, 25% had metabolic and genetic liver diseases (3.3% Dubin Johnson syndrome, 15% glycogen storage disease, and 6.7% Wilson disease), 43.4% were diagnosed with chronic hepatitis [autoimmune hepatitis 20%, chronic hepatitis of unknown etiology 11.7%, steatohepatitis 6.7%, and congenital hepatic fibrosis 5%], 21.6% had infective hepatitis (18.3% HCV and 3.3% HBV), and 10% had cholestatic liver disease (5% Alagille syndrome and 5% progressive familial intrahepatic cholestasis). The studied CLD patients were presented clinically with jaundice (66.6%), abdominal pain (20%), abdominal distention (58.4%), fever (15%), faltering of growth (24.5%), and pallor (16.6%). Abdominal ultrasonography of patients revealed hepatomegaly (80%), splenomegaly (50%), and ascites (6.6%).

All the patients had increased levels of liver enzymes and regard histopathological evaluation of liver biopsy according to the Ishak score revealed that the majority of the studied patients (80%) showed mild disease activity. Regarding the degree of fibrosis, 45% had mild fibrosis (F1), 33.3% had moderate fibrosis (F2), and severe fibrosis (F3) was present in 16.7% of patients (Table 1).

Table 1 Laboratory and histological characteristics of the hepatic group
Full size table

Vitamin D and depression score in CLD patients and controls

There was a statistically significant difference between the studied groups regarding the level of serum 25-OH-vitamin D as it was lower in the hepatic group (Fig. 1 and Table 2). There was a statistically significant difference between studied groups regarding depression score as all degrees of depression (mild, moderate, and severe) were statistically higher in the hepatic group (Table 2).

Fig. 1
figure 1

Serum 25-OH-vitamin D levels in both groups

Full size image
Table 2 Serum 25-OH-vitamin D and depression score among studied groups
Full size table

Regarding liver biopsy, there was a statistically significant association between the serum level of 25-OH-vitamin D and degree of fibrosis (FI) and histological activity index (HAI) as it decreases with increasing degree of fibrosis and HAI. Also, there was a statistically significant association between depression score and degree of fibrosis and HAI as it increases with increasing degree of fibrosis and HAI (Table 3).

Table 3 Relation between both serum 25-OH-vitamin D and depression score and liver biopsy findings
Full size table

There was a statistically significant difference between children with depressive symptoms (38 cases) and non-depressive symptoms (22 cases) regarding the level of serum 25-OH-vitamin D as it was lower in children with depressive symptoms [median (range) 17 (5–40), 27.5 (8–52, p = 0.04) respectively]. There were statistically significant differences between both normal and different degrees of depression regarding the serum level of 25-OH-vitamin D as it decreased with increasing severity of depression (Table 4).

Table 4 Relation between serum 25-OH-vitamin D level and depression score
Full size table

There was a statistically significant negative correlation between 25-OH-vitamin D and ALT, AST, FI, HAI, and depression score, but there were no statistically significant correlations between 25-OH-vitamin D and other clinical and laboratory measures (Table 5).

Table 5 Correlation between 25-OH-vitamin D and degree of depression score and clinical and laboratory measures
Full size table

There was a statistically significant positive correlation between the degree of depression score and ALT, AST, FI, and HAI, while there was a statistically significant negative correlation between the degree of depression score and hemoglobin and albumin. There were no statistically significant differences between the degree of depression score and other variables (Table 5).

Discussion

The present study shows that there was a statistically significant difference between the studied groups as regards the level of serum 25-OH-vitamin D as it was statistically lower in the hepatic group. Seventy-five percent of the control group had sufficient, and 25% had insufficiency of 25-OH-vitamin D. While in the hepatic group, 38.3% had sufficient 25-OH-vitamin D, 41.7% insufficiency, and 20% had deficient 25-OH-vitamin D. Such findings are consistent with Lee et al. [15] who found that vitamin D deficiency was prevalent in children with CLD despite supplementation of vitamin D. Overall, 28% of the subjects were either vitamin D deficient or insufficient. Also, Jamil et al. [16] found that 88% had either insufficient (patients, 52.8% vs. controls, 27%) or deficient levels (patients, 34.4% vs. controls, 26%) of vitamin D, while only 12% had sufficient levels of vitamin D (patients, 12% vs. controls, 47%). Likewise, Arteh et al. [17] reported that the global prevalence of vitamin D deficiency (VDD) in the general population has been reported to effect all age groups ranging from 20 to 100% for serum 25(OH) vitamin D concentrations < 20 ng/ml. The prevalence of vitamin D levels < 20 ng/ml in CLD has been reported to range from 64 to 92% and is generally inversely linked to the progression of the disease.

There are many possible reasons for the reported inverse relationship between liver disease severity and falling vitamin D status. The underlying mechanisms are almost definitely multifactorial in nature and likely to vary between different liver pathologies. Important possible mechanisms to consider are as follows: reduced exogenous exposure of patients to vitamin D sources (e.g., dietary, sunlight), deficiency of bile salts needed for gastrointestinal absorption of vitamin D, reduced endogenous production of vitamin D and albumin which impaired by cirrhosis, impaired hepatic hydroxylation of vitamin D to 25(OH) D, and increased catabolic removal of 25(OH) D [18].

In the current study, there was a statistically significant difference between the studied groups as regards depression score as 30% of the control group had mild depression, while 36% of the hepatic group had mild depression, 16.7% had moderate depression, and 10% had severe depression. Such results follow Akram et al. [19] who recorded that patients suffering from depression were 59.3%, anxiety was 17.4%, and both anxiety and depression were 30.7%. Also, Kerkar et al. [20] found that children with NAFLD have higher levels of depression than those with obese controls, while Arslan et al. [21] found that the mean depression and anxiety scores between children with chronic hepatitis B and control group were not significantly different (p > 0.05).

Relative to many studies of depression prevalence in CLD patients, mechanistic depression research was incomplete. Generally, the main reasons for this include the following aspects: (i) the disease itself: the long-term discomfort caused by illness and treatment, feeling of guilt, and anxiety about the progression of the disease, etc. and (ii) social and economic strain, including basic research and working conditions, social discrimination, and high medical treatment costs. Emerging evidence supported reduced serotonin and dopamine transporter binding in chronic hepatitis patients with cognitive impairment, which could be associated with depression [1].

In the present study, there was statistically significant positive correlation between the degree of depression score and ALT, AST, FI, and HAI; there are many studies run in line with our results and reported that depression was associated with more severe fibrosis and HAI [22,23,24].

In this study, there were statistically significant differences between both normal and different degrees of depression regarding serum level of 25-OH-vitamin D as it decreased with increasing severity of depression; also, there was a statistically significant negative correlation between 25-OH-vitamin D and ALT, AST, FI, HAI and depression score. These findings are supported by Skaaby et al. [25] who reported a statistically significant inverse association between vitamin D status and incident liver disease with a hazard ratio = 0.88 (95% confidence interval 0.79–0.99) per 10 nmol/L higher vitamin D status at baseline. The risk of having a high level of ALT, AST, or GGT appeared to be higher for lower vitamin D levels, but not statistically significant, and they stated that vitamin D status was inversely related to incident liver disease. Also, many studies had reported an inverse association between vitamin D status and degree of liver fibrosis [26, 27], while Yodoshi et al. [28] found that the majority were either vitamin D insufficient (50%) or deficient (32%) within 3 months of their liver biopsy and recorded no association between serum 25(OH)-vitamin D concentrations and serum aminotransferases or histological scores, and they claimed that vitamin D deficiency and insufficiency are common in children with nonalcoholic fatty liver disease (NAFLD), but not consistently linked to severity of histological disease.

Concerning the effect of vitamin D on liver fibrosis, vitamin D has an anti-fibrotic effect on hepatic stellate cells through different signal transduction pathways mediated by receptor vitamin D, which in turn inhibits the expression of pro-fibrogenic genes. Also, some studies showed a significant correlation between low vitamin D levels and an increased risk of hepatic fibrosis. Additionally, the high prevalence of vitamin D deficiency was observed in patients with liver fibrosis, suggesting the use of vitamin D status as a biochemical marker that reflects the progression of liver fibrosis [29].

With regard to the inverse correlation between vitamin D and depression score, these results are consistent with Smith et al. [30] who found that serum 25(OH) vitamin D was negatively associated with Children Depression Inventory (CDI) scores (r = − 0.55, p < 0.001), and the group of patients with insufficient level 25(OH) vitamin D levels did show significantly more depressive symptoms (p < 0.001). Also, many researchers who reported significant improvement in depression and well-being with vitamin D supplementation suggest a link between vitamin D status and depression [31, 32]. Likewise, Sarris et al. [33] have confirmed that vitamin D is recommended for use with antidepressant drugs in successful depression treatment.

Region-specific expression of vitamin D receptors (VDR) in the cingulate cortex, thalamus, cerebellum, substantia nigra, amygdala, and hippocampus suggests the possibility of a function of vitamin D in psychiatric disorders. Many of these regions also express 1α-hydroxylase enzymes capable of metabolizing 25(OH) D to 1,25(OH)2D3, suggesting that vitamin D may play an autocrine or paracrine action in the brain [34]. Indeed, vitamin D may play a key role in the pathophysiology of depression and several studies have shown the existence of vitamin D, its receptors (VDR) and associated enzymes (CYP 24A1, CYP 27B1) in several brain regions, pointing to the importance of vitamin D as a neuroactive/neurosteroid hormone involved in key functions such as neuroprotection, neuroimmunomodulation, regular brain function, and brain development [34, 35]. Also, evidence of possible neuroprotective roles is emerging that vitamin D may play through its effects on inflammation. Certainly, increasing data suggest that the upregulation of proinflammatory cytokines in the brain can be linked with depression [36] and vitamin D may will be one of the modulators in the association between depression and inflammatory response by its impact on the immune system [37].

Strength and limitations

25-OH-vitamin D represents the first step to prove the pivotal role of 25-OH-vitamin D as a marker of depression in chronic liver diseases.

Limitations in our study

Include a small number of cases which make us unable to rebost regression model by sufficient number of predictors and this is from statistical point of view.

Conclusion

Children with chronic liver disease who had depressive symptoms showed a significantly lower level of 25-OH-vitamin D when compared with those without depressive symptoms; also, 25-OH-vitamin D had an inverse correlation with depression score in these children.

Availability of data and materials

All data and materials are available.

Abbreviations

CLD:

Chronic liver diseases

MDD:

Major depressive disorder

FI:

Degree of fibrosis

HAI:

Histological activity index

References

  1. Huang X, Liu X, Yu Y (2017) Depression and chronic liver diseases: are there shared underlying mechanisms? Front Mol Neurosci 10(134):1–11

    Google Scholar 

  2. Gutteling JJ, de Man RA, van der Plas SM, Schalm SW, Busschbach JJ, Darlington AS (2006) Determinants of quality of life in chronic liver patients. Aliment Pharmacol Ther 23:1629–1635

    CAS  PubMed  Article  Google Scholar 

  3. Patten SB, Williams JV, Lavorato DH, Modgill G, Jette N, Eliasziw M (2008) Major depression as a risk factor for chronic disease incidence: longitudinal analyses in a general population cohort. Gen Hosp Psychiatry 30:407–413

    PubMed  Article  Google Scholar 

  4. Mullish BH, Kabir MS, Thursz MR, Dhar A (2014) Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation. Aliment Pharmacol Ther 40:880–892

    CAS  PubMed  Article  Google Scholar 

  5. De Luca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80:1689Se96S

    Google Scholar 

  6. Hogler W, Baumann U, Kelly D (2012) Endocrine and bone metabolic complications in chronic liver disease and after liver transplantation in children. J Pediatr Gastroenterol Nutr 54:313e21

    Article  Google Scholar 

  7. Casseb GAS, Kaster MP, Rodrigues ALS (2019) Potential role of vitamin D for the management of depression and anxiety. CNS Drugs 33:619–637

    CAS  PubMed  Article  Google Scholar 

  8. World Medical Association (2009) Declaration of Helsinki. Ethical principles for medical research involving human subjects. Jahrbuch Für Wissenschaft Und Ethik 14:233–238

    Google Scholar 

  9. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the esophagus for bleeding oesophageal varices. Br J Surg 60:646–649

    CAS  PubMed  Article  Google Scholar 

  10. Kamath PS, Wiesner RH, Malinchoc M et al (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33:464–470

    CAS  PubMed  Article  Google Scholar 

  11. McDiarmid SV, Anand R, Lindblad AS (2002) Development of a pediatric end-stage liver disease score to predict poor outcome in children awaiting liver transplantation. Transplantation 74:173–181

    PubMed  Article  Google Scholar 

  12. Kovacs M. Children’s Depression Inventory (CDI) (1992). North Tonawanda, NY: Multi-Health Systems Inc.

  13. Ghareeb GA, Beshai JA (1989) Arabic version of Children’s Depression Inventory reliability and validity. Journal of clinical child psychology 18(4):322–326

    Google Scholar 

  14. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K et al (2016) Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab 101(2):394–415

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Lee WS, Jalaludin MY, Wong SY, Ong SY, Foo HW, Ng RT (2019) Vitamin D non-sufficiency is prevalent in children with chronic liver disease in a tropical country. Pediatr Neonatol 60(1):12–18

    PubMed  Article  Google Scholar 

  16. Jamil Z, Arif S, Khan A, Durrani AA, Yaqoob N (2018) Vitamin D deficiency and its relationship with Child-Pugh class in patients with chronic liver disease. Journal of clinical and translational hepatology 6(2):135

    PubMed  PubMed Central  Article  Google Scholar 

  17. Arteh J, Narra S, Nair S (2010) Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci 55:2624–2628

    CAS  PubMed  Article  Google Scholar 

  18. Stokes CS, Volmer DA, Grunhage F, Lammert F (2013) Vitamin D in chronic liver disease. Liver Int 33(3):338–352

    CAS  PubMed  Article  Google Scholar 

  19. Akram A, Anwar L, Naeem MT (2017) Evaluation of anxiety and depression in chronic liver disease patients. Journal of Muhammad Medical College, Mirpurkhas 8(2):31–33

    Google Scholar 

  20. Kerkar N, D’Urso C, Van Nostrand K et al (2013) Psychosocial outcomes for children with non-alcoholic fatty liver disease over time and compared with obese controls. J PediatrGastroenterolNutr 56:77–82

    Google Scholar 

  21. Arslan N, Buyukgebiz B, Ozturk Y, Pekcanlar-Akay A (2003) Depression and anxiety in chronic hepatitis B: effect of hepatitis B virus infection on psychological state in childhood. Turk J Pediatr 45(1):26–28

    PubMed  Google Scholar 

  22. Russ TC, Kivimaki M, Morling JR, Starr JM, Stamatakis E, Batty GD (2015) Association between psychological distress and liver disease mortality: a meta-analysis of individual study participants. Gastroenterology 148:958–966.e4. https://doi.org/10.1053/j.gastro.2015.02.004

    PubMed  Article  Google Scholar 

  23. Tomeno W, Kawashima K, Yoneda M, Saito S, Ogawa Y, Honda Y et al (2015) Non-alcoholic fatty liver disease comorbid with major depressive disorder: the pathological features and poor therapeutic efficacy. J GastroenterolHepatol 30:1009–1014. https://doi.org/10.1111/jgh.12897

    Article  Google Scholar 

  24. Youssef NA, Abdelmalek MF, Binks M, Guy CD, Omenetti A, Smith AD et al (2013) Associations of depression, anxiety and antidepressants with histological severity of nonalcoholic fatty liver disease. Liver Int 33:1062–1070

    CAS  PubMed  Article  Google Scholar 

  25. Skaaby T, Husemoen LLN, Borglykke A, Jørgensen T, Thuesen BH, Pisinger C et al (2014) Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine 47(1):213–220

    CAS  PubMed  Article  Google Scholar 

  26. Peng CH, Lee HC, Jiang CB, Hsu CK, Yeung CY, Chan WT et al (2019) Serum vitamin D level is inversely associated with liver fibrosis in post Kasai’s portoenterostomy biliary atresia patients living with native liver. PLoS One 14(6):e0218896

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. Nobili V, Giorgio V, Liccardo D, Bedogni G, Morino G, Alisi A, Cianfarani S (2014) Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease. Eur J Endocrinol 170(4):547–553

    CAS  PubMed  Article  Google Scholar 

  28. Yodoshi T, Orkin S, Arce-Clachar AC, Bramlage K, Liu C, Fei L et al (2019) Vitamin D deficiency: prevalence and association with liver disease severity in pediatric nonalcoholic fatty liver disease. Eur J Clin Nutr:1–9

  29. Udomsinprasert W, Jittikoon J (2019) Vitamin D and liver fibrosis: molecular mechanisms and clinical studies. Biomed Pharmacother 109:1351–1360

    CAS  PubMed  Article  Google Scholar 

  30. Smith BA, Cogswell A, Garcia G (2014) Vitamin D and depressive symptoms in children with cystic fibrosis. Psychosomatics 55(1):76–81

    PubMed  Article  Google Scholar 

  31. Bahrami A, Mazloum SR, Maghsoudi S, Soleimani D, Khayyatzadeh SS, Arekhi S et al (2018) High dose vitamin D supplementation is associated with a reduction in depression score among adolescent girls: a nine-week follow-up study. Journal of dietary supplements 15(2):173–182

    CAS  PubMed  Article  Google Scholar 

  32. Högberg G, Gustafsson SA, Hällström T, Gustafsson T, Klawitter B, Petersson M (2012) Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation. ActaPaediatrica 101(7):779–783

    Google Scholar 

  33. Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, Ng CH (2018) Adjunctive nutraceuticals for depression: a systematic review and meta-analyses. Focus 16(3):328–340

    PubMed  Article  Google Scholar 

  34. Eyles DW, Smith S, Kinobe R et al (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29(1):21–30

    CAS  PubMed  Article  Google Scholar 

  35. Kalueff AV, Tuohimaa P (2007) Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutrit MetabCare 10(1):12–19

    CAS  Article  Google Scholar 

  36. Song C, Wang H (2011) Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog Neuro-Psychopharmacol Biol Psychiatry 35(3):760–768

    CAS  Article  Google Scholar 

  37. van Etten E, Stoffels K, Gysemans C et al (2008) Regulation of vitamin D homeostasis: implications for the immune system. Nutr 66(10 Suppl 2):125–134

    Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

No funding—no grants.

Author information

Affiliations

  1. Pediatrics Department, Faculty of Medicine, Benha University, Benha, Qualiopia, Egypt

    Ola G. Behairy, Al Rawhaa A. Abo Amer & Karim I. Mohamed

  2. Clinical Pathology Department, Faculty of Medicine, Benha University, Benha, Egypt

    Amira I. Mansour

Authors
  1. Ola G. Behairy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Al Rawhaa A. Abo Amer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amira I. Mansour
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karim I. Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

1- O B: contributed to the design and implementation of the research, aided in choosing the patients and helped shape the research, supervised the findings of this work, discussed the results, writing of the manuscript, and read and approved the final manuscript. 2- A A: contributed to the design and implementation of the research, contributed to the revision of the work and the acceptance of the final form of the manuscript, and read and approved the final manuscript. 3- A M: contributed to the design and implementation of the research, performed the laboratory work, and read and approved the final manuscript. 4- K M: contributed to the design and implementation of the research, contributed in the collection of the data and in performing the statistical part of the work, and read and approved the final manuscript.

Corresponding author

Correspondence to Ola G. Behairy.

Ethics declarations

Ethics approval and consent to participate

The study was performed according to the ethical guidelines of the 1975 Declaration of Helsinki. The current study was approved by the Medical Research Ethical Committee of the Faculty of Medicine, Benha University. All subjects were informed about the procedures and the aim of the study, and informed written consent was obtained from the parents or caregivers of enrolled children. The committee’s reference number is not applicable and/or not available.

Consent for publication

Not applicable

Competing interests

None of the authors have any conflicts of interest or financial disclosures related to this work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Behairy, O.G., Abo Amer, A.R.A., Mansour, A.I. et al. Association between vitamin D status and depression in children with chronic liver disease. Egypt Liver Journal 10, 34 (2020). https://doi.org/10.1186/s43066-020-00042-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s43066-020-00042-y

Keywords

  • Children
  • Depression
  • Chronic liver diseases
  • 25-OH-vitamin D