Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic-naive schizophrenia

Abstract

The aim of this study was to explore the relationships between changes in cortical thickness and single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) region in a group of antipsychotic-naive schizophrenia (AN-SCZ) patients. Methods Twenty-five AN-SCZ patients and 51 healthy controls (HCs) participated in this study. General linear models were used to identify associations between the average cortical thicknesses of each brain region (N = 68) and each of the 11 SNPs in the MHC region in the AN-SCZ patients and HCs. Next, we performed independent-sample t tests to investigate whether cortical thickness was significantly lower in the AN-SCZ patients than in HCs in the brain regions that were significantly associated with the SNPs. Finally, we examined the correlations between clinical symptoms and 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 MHC region were significantly associated with cortical thickness only in the AN-SCZ patients; these included rs1635, rs1736913, rs2021722, rs204999, rs2523722, rs3131296, and rs9272105. The AN-SCZ patients had significantly thinner cortical thicknesses in the above brain regions, especially the prefrontal cortex. Furthermore, the left entorhinal region was negatively correlated with Positive and Negative Symptom Scale (PANSS) activation scores in the AN-SCZ group (r = -0.601, p = 0.03). Conclusions This study provides evidence demonstrating the potential effects of MHC risk variants in cortical thickness deficits in AN-SCZ. These data also support the notion that the immune system plays critical roles in the pathology of schizophrenia, which is mediated via the modulation of the development of cerebral cortical structures.

Keywords: antipsychotic-naive schizophrenia; cortical thickness; magnetic resonance imaging; major histocompatibility complex; single nucleotide polymorphisms.