The understanding of the basic physiology of vitamin D functions in the brain is steadily increasing. Studies suggest an association between low levels of vitamin D and the expression of MDD as well as schizophrenia [37, 40]. However, the questions—whether there is a certain cut-off point that could predict the risk for psychiatric disorders, and if vitamin D level is disease specific—are still not answered yet.
Vitamin D status in the patient groups and healthy controls
During the assessment of the current sample, we found vitamin D serum level to be highly significantly lower in patients with MDD compared to controls, where 75% of the MDD patients had vitamin D deficiency/severe deficiency.
In agreement with our results, two studies found that more than half of their samples of depressed patients had low vitamin D levels [32, 37, 43,44,45]. Other studies had equivocal results [44, 46]. For example, one study found no difference in serum vitamin D level between depression and healthy controls [47], which could be attributed to different study design; while we used standardized tool for psychiatric diagnoses, they used register-based diagnoses.
The pathology underlying vitamin D association with depression is a multifactorial one. One psychological proposition suggests that depression is associated with behavioral withdrawal, which would typically reduce outdoor activities and therefore sun exposure potentially leading to vitamin D deficiency [48]. Alternatively, the somatic effects of vitamin D deficiency (fatigue, vague aches) might contribute to a general lowering of mood, which could be viewed as the “psychologization” of somatic symptoms [48].
Additionally, the identification of vitamin D receptors on neurons and glia in various regions of the brain (e.g., hippocampus, cingulate cortex), further support speculations about vitamin D’s relationships with neurotransmitters and psychopathological processes underlying depression [1].
In schizophrenia group, results showed their vitamin D serum level to be statistically significantly lower compared with controls with 55% of the schizophrenia patients had vitamin D deficiency/severe deficiency.
Many studies came in line with our results, linking hypovitaminosis D to psychosis [16, 49,50,51,52,53,54], especially during acute exacerbation of psychotic episodes [55]. Studies also found lower vitamin D levels among schizophrenia patients as compared with those in healthy controls [40, 55,56,57]. However, other research failed to reproduce these findings [58]. For example, in a recent study, although serum vitamin D tended to be lower in the group with schizophrenia than in the control group, this difference did not reach statistical significance. However, this study used a non-clinical sample drawn from the general population, which is more likely to have less severity of psychotic symptoms [47].
In agreement with our results, two studies showed that nearly 65% of patients with schizophrenia had vitamin D deficiency [40, 59].
However, in contrast, a study concluded that the odds of schizophrenia were not different for insufficient versus sufficient subjects [60]. Yet, this study included different ethnic groups, which may have caused this study to give different results from ours.
Like depression, schizophrenia patients are less likely to adopt a healthy lifestyle, with unhealthy dietary patterns which increases the risk for inadequate vitamin D intake. Moreover, they tend to be more sedentary and physically less active than general population, which predisposes them to inadequate ultraviolet-B radiation for vitamin D synthesis [61].
Vitamin D status in the depression group vs. schizophrenia group
The current study showed that patients with schizophrenia had a lower level of vitamin D level when compared with healthy controls; yet, a higher level when compared to patients with MDD. This result is worth noting given that patients with schizophrenia had longer duration of illness and higher number of episodes compared to the MDD group.
Studies comparing vitamin D level between patients with MDD and schizophrenia are scarce. Contrary to our results, a study has concluded that serum vitamin D levels were lower in patients with schizophrenia compared to patients with MDD and to healthy controls [57]. In another study, no differences were found in vitamin D level between schizophrenia and non-psychotic depression [47]. This finding warrants further investigation and needs to be replicated on a wider scale to be confirmed.
Association of low vitamin D levels with demographic and clinical characteristics of the study groups
Results showed that none of the patients’ demographic or clinical variables (the age of presentation, age of onset, duration of illness or the number of previous episodes) were found to be associated with low level of serum vitamin D.
However, the current study revealed that vitamin D serum level was higher in men than in their female counterparts with MDD, schizophrenia, and even controls; yet, it did not reach statistical significance, which may not be detected due to small sample size. These results should be analyzed with caution due to involvement of other cultural and religious factors. For example, the Islamic uniform covering most of the female’ bodies may interfere with their exposure to sunlight which is essential for vitamin D synthesis. This needs further evaluations in future studies.
Like our study, a cohort study found that only women, not men, with low vitamin D levels had significantly higher risk of developing depressed mood during 6 years of follow-up [45]. And it agrees with reports of high rates of vitamin D deficiency in women in general [33].
It is worth noting that the lack of correlation with any of the demographic or clinical variables may indicate that hypovitaminosis D may be a comorbidity rather than a cause or a complication to these diseases. This observation warrants further future investigation.
Diagnostic performance of vitamin D in MDD and schizophrenia
We found that patients with hypovitaminosis D (< 14 ng/ml) are most likely to have MDD or schizophrenia; yet, it cannot be used as a diagnostic test as multiple trials needed to confirm its diagnostic value.
A recent study showed that vitamin D deficiency was an independent predictor for the presence of depression even after adjustment for multiple confounding factors in patients [62].
Another study showed that among women, there was an elevated risk for depression over a broader range of vitamin D deficiency of less or equal to 20 ng/ml in women. For men, however, an elevated risk for depression was true only for a deficiency of lower than 12 ng/ml [63].
In addition, there was non-significant diagnostic performance for vitamin D level in differentiating MDD group from schizophrenia group. Some studies agreed that vitamin D concentration did not differ between schizophrenia or depression [47, 64].
Yet, there is little published evidence directly connecting vitamin D diagnostic value in patients with MDD or schizophrenia.
The contribution of vitamin deficiencies to these processes is not fully understood. Vitamin D deficiency may set the stage for both the onset and the progression of MDD and/or schizophrenia by acting synergistically with other factors as genetics and environmental stressors [21]. Potential aggravation of these processes due to vitamin deficiencies should not be overlooked. Therefore, patient groups at risk for specific vitamin deficiencies should be identified to implement timely and appropriate interventions.
The present study has several limitations; the small sample size and non-random method of sampling suggest that it may not be representative of all patients with MDD or schizophrenia in Egypt. In addition, the cross-sectional nature of the study limits our ability to draw causal inferences. Longitudinal studies are required to determine whether hypovitaminosis D is the cause or the effect. Despite these limitations, the current findings are important in clarifying the relation between MDD, schizophrenia, and vitamin D, which will provide guidance for future research. Moreover, it is one of the few studies to compare between vitamin D level in MDD and schizophrenia.