Evidence-Based Reviews

Vitamin D deficiency and psychiatric illness

Current Psychiatry. 2013 April;12(4):18-27

References

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Psychotic disorders

Several epidemiologic studies have linked low vitamin D levels to schizophrenia and other psychotic disorders. Researchers in Norway who used a structured clinical interview to identify psychosis consistently found low levels of 25(OH)D among immigrants and native Norwegians with psychotic symptoms.²⁰ A study of 8,411 Swedish women found low vitamin D levels were associated with psychotic symptoms.²¹ The Finnish birth cohort study found that use of vitamin D supplementation during the first year of life reduced the incidence of schizophrenia.²² In another pilot study, researchers measured third-trimester serum 25(OH)D levels and found that low levels of maternal vitamin D may be associated with an increased risk of schizophrenia.²³ These studies suggest that low prenatal vitamin D levels may adversely impact the developing brain, increasing the risk for adult-onset schizophrenia.

Clinical Point

Epidemiologic studies have linked low vitamin D levels to schizophrenia and other psychotic disorders

Cognitive dysfunction

Low vitamin D concentrations have been associated with impairments in cognitive functions such as memory and orientation,²⁴ executive function impairments,²⁵ and Alzheimer’s disease (AD).²⁶ A large study conducted from 1998 to 2006 in Italy concluded that persons with severe vitamin D deficiency (<25 nmol/L) had a higher risk of substantial decline on Mini-Mental State Examination than those with sufficient levels (≥75 nmol/L).²⁷ Other studies have linked low vitamin D levels to poor cognitive performance in depressed older adults.²⁸ Low vitamin D levels in older women have been associated with risk of AD, but not with other dementias.²⁹ Polymorphisms of VDR have been associated with depression and poor cognitive performance.³⁰

Depression

Epidemiologic studies evaluating vitamin D deficiency have had conflicting results. The Third National Health and Nutrition Examination Survey, which used a sample of 7,970 non-institutionalized U.S. residents age 15 to 39, demonstrated that individuals with serum vitamin D ≤50 nmol/L are at a significantly higher risk of developing depression than those with vitamin D ≥75 nmol/L.³¹ A study of 1,282 adults age 65 to 95 in the Netherlands found that 25(OH)D levels were 14% lower in depressed patients compared with controls.³² However, a large epidemiologic study in China did not detect a relationship between vitamin D and depression in 3,262 men and women age 50 to 70.³³ After researchers adjusted for geography, body mass index, physical activity, and smoking, 25(OH)D levels did not correlate significantly with the presence or severity of depression. In a case series,³⁴ after 48 vitamin D-deficient depressed adolescents were given vitamin D₃ over 3 months, there was a significant improvement in well-being, depressive symptoms, irritability, and fatigue.³⁴ Other small, cross-sectional studies have examined associations between vitamin D status and depression with divergent results, which may reflect differences in population and methodology.

Clinical Point

Supplemental vitamin D significantly improved depressive symptoms in 1 RCT but not in another

Prospective interventional studies. Although direct causal relationships are difficult to establish, several prospective studies have tested the hypothesis that treating vitamin D deficiency can improve depressive symptoms.

In a double-blind, controlled trial, Jorde et al³⁵ randomized 441 individuals age 21 to 70 to vitamin D, 20,000 IU per week; vitamin D, 40,000 IU per week; or placebo for 1 year. Individuals with serum 25(OH)D levels <40 nmol/L scored significantly higher on depression rating scales than those with serum 25(OH)D levels ≥40 nmol/L at the end of the study. There was no significant improvement in depression ratings in the placebo group (Table 2).³⁵ These results must be interpreted with care because depressive symptoms were secondary endpoints in this study.

Table 2

Effect of vitamin D supplementation on depressive symptoms in a controlled trial

Vitamin D Supplementation	Serum 25(OH)D levels at baseline	BDI total score, Median and range at end of study	After 1 year of vitamin D supplementation
20,000 IU/week	<40 nmol/L	Significantly higher (more depressive traits), 6.0 (0 to 23)	Significantly improved BDI score
40,000 IU/week	≥40 nmol/L	4.5 (0 to 28)	Significantly improved BDI score
Placebo	-	-	No improvement in BDI score
25(OH)D: 25-hydroxyvitamin D; BDI: Beck Depression Inventory Source: Reference 35

Kjærgaard et al³⁶ systematically examined vitamin D levels in a case-control study followed by a randomized controlled trial (RCT) of 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 D₃ 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 depressive symptom scores.

Clinical Point

Seasonal variation in vitamin D levels suggests that supplementation may help patients who have seasonal mood disturbances