Abstract
Background: Schizophrenia and bipolar spectrum disorders (SZBD) are devastating mental disorders with unknown cause and suboptimal treatment. Vitamin D (25OHD) deficiency during development is considered a risk factor for developing schizophrenia and neonatal 25OHD status has been linked to the disorder (McGrath et al. 2010. Schizophr Bull, 36). Psychosis patients more often have sub-optimal 25OHD status and low S-25OHD has been linked to depression and negative symptoms (Nerhus et al. 2016. Schizophr Res). Vitamin D receptors and the 1alpha -hydroxylase enzyme are found in human hippocampus tissue (Eyles et al. 2005. J Chem Neuroanat, 29). Recent reports have shown positive correlation between the right hippocampus and S-25OHD (Shivakumar et al. 2015. Psychiatry Res, 233) as well as age-related hippocampus volume decline (Pujol et al. 2014. Br J Psychiatry, 205) in schizophrenia. To examine a potential role of S-25OHD in age-related hippocampus decline, SZBD patients and healthy controls (HC) were investigated for S-25OHD and hippocampus volume across the age range. Methods: 71 SZBD patients (ages 18–64 y, mean 31.4 y; mean 25OHD: 53.6 nmol/l, 56.3% females) and 95 HC (ages 18–46 y, mean 31.6 y; mean 25OHD: 53.9 nmol/l, 40.0% females), all Caucasian, underwent MRI on the same 3T scanner. Hippocampus volumes were obtained from FreeSurfer; total hippocampus volume (THV) = left + right hippocampus volume. Multiple linear regression was used to examine the contribution of 25OHD, 25OHD by age, age, age by group, group and gender (centered continuous variables) on THV. Subgroup analyses were conducted. The study population was limited to those with S-25OHD measures within 6 weeks of MRI, or maximum 3 weeks’ cross season discrepancy (Winter: November–April, Summer: May–October). Results: THV was significantly associated with 25OHD by age (b = −.8, 95% CI = (−1.3, −.3), P = 2.5e-3), age (b = 24.2, 95% CI = (5.8, 42.5), P = 1.0e-2), age by group (b = −35.7, 95% CI = (−59.1, −12.3), P = 3.0e-3) (SZBD < HC), group (b = −415.5, 95% CI = (−639.9, −191.2), P = 3.5e-4) (SZBD < HC), gender (b = 795.8, 95% CI = (570.8, 1020.9), P = 7.4e-11) (males > females) and trend significant for 25OHD (b = 5.4, 95% CI = (−0.2, 11.1), P = 5.9e-2). The overall model was significant (adj. R(2) = .36, F(6,159) = 16.2, P < 1e-13). Subgroup analysis show a significant 25OHD and 25OHD by age association in the SZBD group. Conclusion: The results indicate that SZBD follow a different aging trajectory than HC with age-related steeper decline in hippocampus volume as previously reported in (Pujol et al. 2014. Br J Psychiatry, 205). 25OHD positively influence THV in younger persons and this influence is reduced with increasing age. Subgroup analysis indicate that the 25OHD association is present only in the SZBD group. In HC group: inconclusive due to limited age-range. This age-related decline in the influence of 25OHD on THV in SZBD could relate to a disease mechanism and warrant further investigation.