Altered cortical thickness related to single nucleotide polymorphisms in the human leukocyte antigen in antipsychotic-naive schizophrenia

Abstract

Objective To explore the relationship between changes in cortical thickness and single nucleotide polymorphisms(SNPs) in the human leukocyte antigen(HLA) in a group of antipsychotic-naive schizophrenia (AN-SCZ) patients. Methods Twenty-five chronically ill AN-SCZ patients and 51 healthy controls (HCs) were recruited and studied from May 2014 to July 2016. All participants received 3.0 T MR head scans and blood collection to obtain high resolution T1WI images and detailed genetic data. Next, we extracted and averaged the values of cortical thickness from each brain region(n=68) for each participant by FreeSurfer and then used general linear models to explore the relationship of each SNP with cortical thickness in the AN-SCZ and HCs while including age, gender and duration of disease in the models as covariates. In the next step, we applied an independent-samples t-test with a threshold of 0.05 to explore whether the cortical thicknesses differed significantly between the AN-SCZ and HCs in the brain regions that were significantly associated with the SNPs in the MHC. Finally, we examined the correlation of clinical symptoms with cortical thickness in the above brain areas in the whole AN-SCZ group using Pearson correlation tests. Results Seven of the 11 SNPs within the HLA regions exhibited significant associations with the cortical thickness only in the AN-SCZ patients, including rs1635, rs1736913, rs2021722, rs204999, rs2523722, rs3131296 and rs9272105. Furthermore, the AN-SCZ patients also exhibited significant reductions in cortical thickness in the above brain regions, which included the left entorhinal cortex, the left pars triangularis cortex, the left rostral middle frontal cortex, the right lateral occipital cortex, the right medial orbitofrontal cortex, the gray matter surrounding the right calcarine gyrus, the right rostral middle frontal cortex, the right frontal pole and the caudal part of the right anterior cingulate. The left entorhinal region also exhibited a negative correlation with PANSS activation scores in the AN-SCZ(r=-0.601, P=0.03). Conclusion The present study provided evidence for the significant association of HLA risk variants with cortical thickness in AN-SCZ. Key words: Schizophrenia; Magnetic resonance imaging; Polymorphism, single nucleotide; HLA antigens