LOW LEVELS OF VITAMIN D ARE ASSOCIATED WITH REDUCED CORTICAL THICKNESS AND SURFACE AREA IN FRONTAL, TEMPORAL AND OCCIPITAL REGIONS IN FIRST-EPISODE PSYCHOSIS PATIENTS

Abstract Background Vitamin D is a neuro-steroid hormone important in brain development, maturation and function as it modulates the production of numerous brain growth factors. Indeed insufficient levels seem to compromise brain development and confer an increased risk of developing schizophrenia later on in life. Finally patients with first-episode psychosis tend to have lower levels of vitamin D than healthy controls. We aimed to explore: 1) The association between vitamin levels and brain structure (i.e. cortical thickness and surface area) in FEP individuals; 2) Differences in brain structure (i.e. cortical thickness and surface area) between FEP individuals with optimal and sub-optimal levels of Vitamin D. Methods Sample: 49 patients with first episode of psychosis (mean age: 27.8 SD ± 9.1 years) part of the BRC Psychosis Theme study on Genetics and Psychosis (GAP). Vitamin D: Vitamin D (serum 25-hydroxyvitamin D) levels were determined by immunoassay. Patients were considered to have sub-optimal levels if vitamin D concentration was below 20 ng/ml, with higher concentrations deemed optimal. Twenty patients had sub-optimal levels of Vitamin D whereas 29 had optimal Vitamin D concentration. Brain Structure: 3T MRI scan were used to evaluate the cortical thickness and the surface area in 49 FEP patients. FreeSurfer 5.3.0 was used to correlate Vitamin D levels with both cortical thickness and surface area in a vertex-by-vertex analysis. afterwards differences in cortical thickness and surface area between FEP participants with both optimal and sub-optimal Vitamin D levels were examined using a vertex-by-vertex General Linear Model analysis in FreeSurfer 5.3.0. Results were corrected for multiples comparison with Montecarlo simulation. Results Vitamin D levels positively correlated with cortical thickness in the left superior-frontal gyrus and surface area in the right peri-calcarine and right inferior-parietal gyrus (all p<0.05 FWE corrected). FEP patients with sub-optimal levels of Vitamin D (below 20 ng/ml) had reduced cortical thickness in the right medial-orbitofrontal gyrus and lingual gyrus compared to those with optimal levels of Vitamin D (all p<0.05 FWE corrected). Additionally, FEP patients with sub-optimal levels of Vitamin D had smaller surface areas in the cuneus, latero-orbitofrontal gyrus, pre- and post central gyri, superio-frontal gyrus, and inferio parietal gyrus in the right hemisphere than those with optimal levels (all p<0.05 FWE corrected). Discussion Vitamin D levels are associated with reduced cortical thickness and smaller surface area in frontal, temporal, parietal and occipital brain regions in individuals with FEP. Interestingly, these areas complete their maturation well into late adolescence, thus potentially being exposed to low Vitamin D levels over a long period of time may contribute to specific brain structure in adulthood. The identification of a specific brain conformation associated to low levels of Vitamin D would promote greater understanding of the interface between physical and mental illness fostering the development of precision psychiatry.