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Vitamin D and folate deficiency are considered risk factors for schizophrenia and bipolar disorders, but it is unknown how vitamin D and folate influence the growing brain, cranium or the clinical phenotype. Serum vitamin D and folate levels are in part genetically regulated. We investigated whether adult vitamin D and folate levels are associated with the intracranial volume (ICV) under the hypothesis that developmental vitamin D or folate levels influence neurodevelopment and that current levels are associated with ICV.

Ninety patients with severe mental disorders and 91 healthy controls underwent 3 T magnetic resonance imaging and serum sampling. Multiple linear regression was used to assess the contribution of serum vitamin D, folate and patient-control status on ICV. We show that vitamin D levels were within lower range for patients and controls (48.8 ± 22.1 nmol/l and 53.4 ± 20.0 nmol/l, respectively). A significant positive association was found between vitamin D and ICV (p = 0.003, r = 0.22), folate was trend-significantly associated with ICV. Folate and vitamin D were significantly associated (p = 0.0001, r = 0.28). There were nonsignificant patient-control differences and no interaction effects. The results suggest that Vitamin D is associated with ICV as detected in the adult.

Further studies are warranted for replication and to investigate possible mechanisms and genetic associations. The size of the intracranial volume (ICV) depends on the developing brain and is considered fully grown by early adolescence. Severe mental disorders such as schizophrenia and bipolar disorders have been hypothesized to be part of a neurodevelopmental continuum. Recent meta-analyses indicate significantly smaller ICV in schizophrenia when compared to controls,, but this has not been demonstrated for bipolar disorder. Smaller ICV in schizophrenia could suggest abnormal brain development prenatally, in childhood or in early adolescence, i.e. Prior to psychosis onset in the majority of patients. Although the causal reason for smaller ICV is unknown, one hypothesis relates it to developmental nutritional deficiencies during gestation, childhood or adolescence.

A small study supports this notion by indicating smaller ICV in schizophrenia patients exposed to prenatal famine. There is less evidence of aberrant neurodevelopment for bipolar disorder. Schizophrenia and bipolar disorder have been suggested to be part of a heterogeneous schizophrenia-bipolar spectrum. Epidemiological studies indicate that developmental nutritional deficiencies e.g.

Due to maternal famine or winter-spring births are associated with increased risk for offspring with schizophrenia, and bipolar disorder. This was supported by a Swedish register study where inadequate gestational weight gain, a proxy for inadequate maternal nutrition, was associated with higher risk for offspring with non-affective psychosis. Developmental serum vitamin D and serum folate (S-folate) deficiencies are considered risk factors for the development of schizophrenia.

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