Vitamin D Blog: Low D Levels in Schizophrenia

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Vitamin D-deficient individuals are more than twice as likely to be diagnosed with schizophrenia compared with people with levels normally considered sufficient, a meta-analysis found.

The research, which analyzed 19 observational studies, is the first comprehensive systematic review and meta-analysis investigating vitamin D levels (usually the active compound 25-hydroxyvitamin D or 25-OH-D) and schizophrenia, the authors said.

"Although the role of vitamin D in schizophrenia has been investigated in several epidemiological studies, data are conflicting," according to Ahmad Esmaillzadeh, PhD, and colleagues from the Isfahan University of Medical Sciences in Iran, writing online in the Journal of Clinical Endocrinology & Metabolism.

The meta-analysis included eight cross-sectional studies, 10 case-control studies, and one nested case-control study. Sample sizes of the studies ranged from 17 to 848 people, with a total of 2,804 participants 18 to 65 years old. Papers were published between 1988 and 2013, and 11 of them were reported from European countries.

Although most studies reported lower serum vitamin D levels in schizophrenic patients, the associations did not reach statistical significance in some cases.

Meta-analysis findings on means of serum levels of vitamin D between schizophrenic patients and controls revealed an overall mean difference of -5.91 ng/mL (95% CI minus 10.68-minus 1.14).

Significant mean differences were seen in case-control studies, European and non-European studies, and studies that included inpatients.

But differences in cross-sectional studies and those that included outpatients did not reach significance.

The overall prevalence of vitamin D deficiency in schizophrenic patients was 65.3% (95% CI 46.4-84.2%). Prevalence of vitamin D deficiency in healthy individuals around the world is upwards of 30% to 50%.

Meta-analysis on odd ratios showed that vitamin D-deficient individuals were 2.16 times (95% CI 1.32-3.56) more likely to be diagnosed with schizophrenia than those who were vitamin D-sufficient.

However, a major limitation of the analysis was that the individual studies used different definitions of "deficiency" and "insufficiency"; some reported mean values for 25-OH-D levels whereas others merely gave prevalences of deficiency and insufficiency, according to the individual studies' criteria. "Normal" was typically defined as a 25-OH-D level of 30 ng/mL.

Why vitamin D deficiency might be associated with schizophrenia is unclear, write the study's authors.

Earlier ecological findings have reported the higher prevalence of schizophrenia in higher latitudes, colder climates, and dark-skinned people, Esmaillzadeh told MedPage Today. These populations may have reduced cutaneous synthesis of vitamin D from sun exposure.

The findings do not imply causation, warned Esmaillzadeh.

Indeed, there appear to be relevant variables for which the group did not control.

They included comorbidities, psychiatric medications, and overall nutritional status. Schizophrenic patients tend to gain substantial weight from antipsychotic medications, which can lead to decreased vitamin D levels. Many anti-seizure medications are also associated with vitamin D deficiencies, the authors wrote.

It is also possible that inpatients were vitamin D-deficient from lack of exposure to sunlight.

Other limitations came from significant between-study heterogeneity. Results were from subgroup analyses and based on study design, location, type of biomarker assessed, patient hospitalization status, and study quality.

The control groups were different: in case-control studies controls were healthy subjects with no history of psychiatric disorders, but in cross-sectional studies, controls were psychiatric patients other than those with schizophrenia.

Also, researchers were unable to access some studies' full text so they used abstracts instead, the researchers noted.
