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Do children with mental disorders have higher prevalence of hypovitaminosis D?

[version 1; peer review: 1 approved, 2 approved with reservations]
PUBLISHED 17 Jul 2013
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Abstract

Inadequate vitamin D level is associated with various adverse medical outcomes. There is a growing concern that insufficient vitamin D may play a role in the development of psychiatric symptoms. This study aims to answer the question: do children with mental disorders have a higher prevalence of hypovitaminosis D? A retrospective chart review examined 25 hydroxyvitamin D (25(OH)D) levels in youth ages 7 to 17 (n=67) at two Oregon psychiatric residential facilities. Vitamin D deficiency is defined as <20 ng/ml and insufficiency as <30 ng/ml. Diagnoses were organized into six categories. 25(OH)D levels were compared across genders and diagnostic groups using a two-sample t-test and ANOVA, respectively. Statistical differences in prevalence across diagnostic categories were calculated using a Pearson chi-square test. Using the data from Saintonge’s NHANES III study on healthy US children for comparison, 21% of our cohorts were found to be vitamin D deficient and 64% insufficient, in contrast to 14% and 48%, respectively. While our results are not statistically significant, mainly because of small sample size, the overall mean 25(OH)D level in our cohort was insufficient (27.59 ± 9.35 ng/ml), compared to a sufficient mean value of 32.1 ng/ml in the general population. No statistical significant difference was found in the prevalence across diagnostic categories. This study found that children with psychiatric disorders might have a higher prevalence of hypovitaminosis D than the general pediatric population. Although a causal relationship between hypovitaminosis D and psychiatric disorders cannot be derived based on the study design, our study provides initial descriptive data on the prevalence of hypovitaminosis D in children with psychiatric disorders, which has not been previously reported to our knowledge. Prospective studies with a larger sample size and controlled variables would allow more precise analysis of the relationship between hypovitaminosis D and childhood mental disorders.

Keywords

Vitamin D, mental illness, psychoses, autism, mood, insufficiency, deficiency, 25(OH)D, paediatric

Introduction

An inadequate vitamin D level is increasingly being linked to diverse disease states. Beyond its importance in endocrine and bone health, there is a growing concern that vitamin D insufficiency may affect brain function and mental health.

Studies have linked hypovitaminosis D to various psychiatric disorders such as depressed mood1 and schizophrenia2,3. In children, emerging evidence suggests that vitamin D plays a role in brain development46. A Finnish study found that vitamin D supplementation in infancy reduced the risk of schizophrenia later in life among males7. A Swedish study found that patients diagnosed with schizophrenia and autism had the lowest 25-hydroxyvitamin D (25(OH)D) levels among psychiatric diagnoses, and proposed that low 25(OH)D may not only be a predisposing developmental factor, but may also affect mental health in adulthood3. Therefore, prevention of hypovitaminosis D in early life may be associated with reduced risk of developing certain psychiatric disorders.

The optimal level of vitamin D is controversial. The cutoff serum levels range from 20 to 50 ng/ml8. The American Academy of Pediatrics (AAP) recommends a minimal level of 20 ng/ml in children. Using the same cut-off value, the US Institute of Medicine (IOM) reports that the majority of North Americans have sufficient vitamin D required for bone health8. However, some subgroups, particularly those who are older, those living in institutions, or those with darker skin, may be at increased risk for hypovitaminosis D8.

Vitamin D insufficiency in the general population was estimated to range from 1% to 78% among different studies9. Using the Third National Health and Nutrient Examination Survey (NHANES III, 1988–94) data, Saintonge et al. estimated that 14% of healthy children had 25(OH)D levels below 20 ng/ml, and 48% had levels below 30 ng/ml10. The prevalence of hypovitaminosis D among children with mental disorders remains unclear.

This study attempts to ascertain whether children with mental illness have a higher prevalence of hypovitaminosis D and whether there is a difference in prevalence across various disorders.

Methods

A retrospective chart review was conducted at two residential psychiatric treatment programs in Oregon, USA, (latitude 45°N). There were 67 patients aged from 7 to 17 years, whose serum 25(OH)D levels were measured between October 2009 and 2010. Patients had one to four co-morbid psychiatric diagnoses. There were no exclusion criteria. Given the retrospective nature and lack of identifiable health data used in the study, no institutional review board approval was needed.

Deficiency was defined as <20 ng/ml, based on the AAP recommended value. Insufficiency was defined as <30 ng/ml, by the local laboratory standard used in Oregon. For the 14 patients who had multiple 25(OH)D levels recorded, we used the lowest 25(OH)D level in our analyses. We felt this method was justified clinically if any period with this degree of hypovitaminosis D during childhood is correlated to developmental differences. The diagnoses were organized into six categories shown in Table 1. For patients with multiple diagnoses, their 25(OH)D level was counted individually in each diagnostic category to calculate the mean and prevalence.

Table 1. Diagnostic categories.

CategoryDiagnoses included
Anxiety disorder• Anxiety Post traumatic stress disorder
• Obsessive compulsive disorder
• Post traumatic stress disorder
Autism spectrum disorders (ASD)• Autism
• Asperger's syndrome
• Pervasive developmental disorder
Disruptive disorders• Attention deficit/hyperactive disorder (ADD/ADHD)
• Conduct disorder
• Disruptive disorder not otherwise specified (NOS)
• Intermittent explosive disorder
• Oppositional defiant disorder
Mood disorders• Bipolar disorder I and II
• Cyclothymia
• Major depression
Psychotic disorders• Psychotic disorder NOS
• Schizoaffective disorder
• Schizophrenia
Other disorders• Acculturation problem
• Cognitive disorder
• Eating disorder
• Enuresis
• Language/communication disorder
• Learning disorder
• Relational problem
• Sleep disorder
• Substance abuse and dependence

25(OH)D levels were compared across genders and diagnostic groups using a two-sample t-test and ANOVA, respectively. Statistical differences in prevalence across diagnostic groups were calculated using a Pearson chi-square test. The analysis was performed using STATA IC (version 11) from StataCorp LP, College Station, Texas.

Results

A total of 67 patients with 168 diagnoses were included in this study. Using the NHANES III study10 for comparison, 21% of our cohort were vitamin D deficient (<20 ng/ml), compared to 14% reported in the general US population. If a cut-off value of 30 ng/ml was used, 64% of the children in our study population were classified as being insufficient, compared to 48% of healthy US children.

The overall mean 25(OH)D level in our study cohort was 27.59 ± 9.35 ng/ml (i.e. insufficient), compared to a mean value of 32.1 ng/ml (i.e. sufficient) in the general US population10. Females in our study (n=29) had a mean level of 27.4 ± 9.1 ng/ml, comparable to the mean of 27.74 ± 9.66 ng/ml amongst males (n=38). The gender difference was non-significant (p=0.89). The mean 25(OH)D levels by diagnostic category are shown in Table 2. No statistical significant differences could be concluded in the mean level (p=0.80) across diagnostic categories.

Table 2. Percent and mean 25(OH)D level by diagnostic categories.

CategoryPercent of study cohort
(n=168)
Mean 25(OHD) level
(ng/ml)
Std. dev. (ng/ml)
Anxiety disorder18% (n=30)27.8910.58
Autism spectrum disorders
(ASD)
9% (n=15)29.7211.58
Disruptive disorders27% (n=46)27.276.74
Mood disorders27% (n=45)28.9610.11
Psychotic disorders4% (n=7)26.4712.42
Other disorders15% (n=25)26.0210.85

The prevalence of patients with hypovitaminosis D across diagnostic groups using both cutoff values are shown in Figure 1. There was no statistical significance found in the prevalence across diagnostic groups, perhaps due to the small sample size. It is interesting to note that psychotic disorder had the highest prevalence of deficiency and insufficiency among specific diagnostic groups: 43% and 71%, respectively.

23cc1b3f-4d74-42a5-a0e4-d54232df2621_figure1.gif

Figure 1. Prevalence of 25(OH)D deficiency (p=0.28) and insufficiency (p=0.72) across diagnostic categories in a pediatric population with mental disorders.

Values are given as percentages. See Table 1 for a list of ‘Other Disorders’.

Discussion

Beyond its importance in endocrine function, there is growing awareness of the role that vitamin D plays in brain function. However, the prevalence of hypovitaminosis D in children with mental illnesses is uncertain. This study found that children with serious psychiatric disorders may have a higher prevalence of hypovitaminosis D and a lower mean 25(OH)D level, compared to the general US population10. Although no statistical significance can be concluded, it is noteworthy that psychotic disorders had the highest prevalence of hypovitaminosis D among the specific diagnostic categories, which supports previous studies2,3,7. We suggest using a cut-off value of 20 ng/ml for clinical interventions, as recommended by the AAP and IOM10. Clinicians should discuss the costs and benefits of treatment with patients when levels are between 20 and 30 ng/ml.

The primary limitation of this study was its small sample size. Due to its retrospective design, we were limited by the availability of 25(OH)D studies without specific clinical indications. Other limitations include not controlling for the length of inpatient stay, ethnicity, age, nutritional status, sun exposure, or skin pigmentation. For the patients with multiple diagnoses, their 25(OH)D was counted in each diagnostic category, which might overestimate the prevalence of hypovitaminosis D. The study utilized the lowest level of 25(OH)D for patients with multiple measurements, which might result in lower mean level and higher prevalence. Although a causal relationship between hypovitaminosis D and psychiatric disorders cannot be derived based on the study design, our study provides important initial descriptive data on the prevalence of hypovitaminosis D in a pediatric population with psychiatric disorders which has not, to our knowledge, been previously reported.

Conclusion

As research continues on the impact of vitamin D in medicine, its implication for psychiatric disorders may be clarified. While no robust statistical conclusions can be made mainly due to small sample size, this study provides initial data suggesting that children with mental illnesses might have lower vitamin D levels and a higher prevalence of hypovitaminosis D than the general population.

Given the high prevalence of hypovitaminosis D and its profound impact on overall health, clinicians should have a higher suspicion of hypovitaminosis D in the pediatric psychiatric population.

Important future steps include the design of a larger prospective study with more controlled variables would allow more precise analysis to establish the prevalence of hypovitaminosis D, as well as to infer any correlation between hypovitaminosis D and childhood mental illness. Preventative and ameliorative measures might subsequently be instigated to assess causation and affect the development and treatment of certain mental disorders.

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Zhang M, Cheng K, Rope R et al. Do children with mental disorders have higher prevalence of hypovitaminosis D? [version 1; peer review: 1 approved, 2 approved with reservations]. F1000Research 2013, 2:159 (https://doi.org/10.12688/f1000research.2-159.v1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 17 Jul 2013
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Reviewer Report 31 Jul 2013
Hans-Peter Volz, School for Psychiatry and Psychotherapy, Hospital for Psychiatry, Psychotherapy and Psychosomatic Medicine Schloss Werneck, Bavaria, Germany 
Approved with Reservations
VIEWS 15
  • The authors should clearly state whether they included all patients of this age group or whether the included patients represent a sub-sample; if yes, according to which inclusion criteria?

  • Since patients with multiple diagnoses have been counted in each diagnostic category
... Continue reading
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CITE
HOW TO CITE THIS REPORT
Volz HP. Reviewer Report For: Do children with mental disorders have higher prevalence of hypovitaminosis D? [version 1; peer review: 1 approved, 2 approved with reservations]. F1000Research 2013, 2:159 (https://doi.org/10.5256/f1000research.1765.r1112)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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16
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Reviewer Report 25 Jul 2013
Linda Mayes, Yale University, New Haven CT, USA 
Approved with Reservations
VIEWS 16
While the report offers an interesting hypothesis, the sample is under-powered and the findings are not significant. There are also many biases in why vitamin D levels were or were not measured in psychiatric samples. The authors note limitation of ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Mayes L. Reviewer Report For: Do children with mental disorders have higher prevalence of hypovitaminosis D? [version 1; peer review: 1 approved, 2 approved with reservations]. F1000Research 2013, 2:159 (https://doi.org/10.5256/f1000research.1765.r1117)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 29 Jul 2013
    Mini Zhang, Department of Psychiatry, Oregon Health and Science University, Portland OR, 97239, USA
    29 Jul 2013
    Author Response
    Dear Dr. Mayes, 

    Thank you for your comments and suggestions. We are aware of several limitations of our study including the sample size and the method of vitamin D measurement, as ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 29 Jul 2013
    Mini Zhang, Department of Psychiatry, Oregon Health and Science University, Portland OR, 97239, USA
    29 Jul 2013
    Author Response
    Dear Dr. Mayes, 

    Thank you for your comments and suggestions. We are aware of several limitations of our study including the sample size and the method of vitamin D measurement, as ... Continue reading
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11
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Reviewer Report 23 Jul 2013
Shailesh Jain, Texas Tech University, Lubbock TX, USA 
Approved
VIEWS 11
The title of the article is appropriate to the content of the article.  

The abstract is able to summarize the key elements of the research including the brief overview of the study design, statistical methods used and the key conclusion. 

The article ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Jain S. Reviewer Report For: Do children with mental disorders have higher prevalence of hypovitaminosis D? [version 1; peer review: 1 approved, 2 approved with reservations]. F1000Research 2013, 2:159 (https://doi.org/10.5256/f1000research.1765.r1188)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 25 Jul 2013
    Mini Zhang, Department of Psychiatry, Oregon Health and Science University, Portland OR, 97239, USA
    25 Jul 2013
    Author Response
    Dear Dr. Jain, 

    Thank you very much for your nice words and comments! We appreciate your time and expertise in reviewing our article. 

    Please feel free to contact me if you have ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 25 Jul 2013
    Mini Zhang, Department of Psychiatry, Oregon Health and Science University, Portland OR, 97239, USA
    25 Jul 2013
    Author Response
    Dear Dr. Jain, 

    Thank you very much for your nice words and comments! We appreciate your time and expertise in reviewing our article. 

    Please feel free to contact me if you have ... Continue reading

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 17 Jul 2013
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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