Altered cortical thickness related to the SNPs on the major histocompatibility complex in never-medicated schizophrenia
Bo Tao1, Yuan Xiao1, Lu Liu1, Li Yao1, Wenjing Zhang1, and Su Lui1

1Radiology, West China Hospital of SiChuan University, Chengdu, China, People's Republic of

Synopsis

In summary, the present study provided evidence that single nucleotide polymorphisms(SNPs) on the major histocompatibility (MHC) relate with cortical thickness deficits in several regions,which support the critical role of immune system in the pathology of schizophrenia via modulation the development of the cerebral cortical structure.

Introduction:

Schizophrenia (SZ) is a hereditary brain disorder with abnormal genetic variants and wide spread gray matter deficits, especially involving the frontal and temporal cortices. However, the relationship between these genetic variants and the brain deficits is unclear. Single nucleotide polymorphisms (SNPs) on the major histocompatibility complex (MHC) have been reported to be related to the onset of schizophrenia. Thus, the aim of this study is to explore the relationship between the changes of cortical thickness and the SNPs on MHC in a group of never-medicated schizophrenia.

Method:

The study was approved by the local ethical committee and written informed consent was obtained from all subjects. 27 never-medicated schizophrenia patients and 28 healthy comparison subjects were recruited from. Besides, the diagnosis of SZ was confirmed in interviews with a experienced psychiatrists using the Structured Clinical Interview for DSM-IV. All participants were performed MR examination via a 3-Telsa GE MRI system with an 8 channel phase array head coil. The single nucleotide polymorphisms (SNPs) on the major histocompatibility (MHC) including rs1635, rs204999, rs6932590, rs9272105, rs886424, rs926300, rs1736913, rs2021722, rs2523722, rs3131296, rs3800316 1 were examined, using genome-wide association studies (GWAS). The FreeSurfer package (version 5.1.0, http://surfer.nmr.mgh.harvard.edu/) is employed to extract cortical thickness measurements from T1-weighted MR images.Firstly, we explore cortical deficits and SNPs on MHC separately in SZ, and then use linear regression model to explore the relationship between SNPs and these cortical deficits (P<0.05).

Results:

First, SZ showed decreased cortical thickness in left superior temporal gyrus, right pars triangularis, right insula, right frontopolar, right subgenual, right dorsal anterior cingulate and right middle fronta gyrus in relative to healthy controls(P<0.05) (Figure 1). The linear regression model analysis showed that three SNPs on MHC (rs204999G, rs6932590C, rs9272105A) have significant association with decreased cortical thickness in SZ. The A allele of rs9272105 is correlated with cortical thickness of the right middle frontal and the right frontopolar cortices, while changes in the right insula shows a linear relation with the A allele of rs6932590. It was also found that the G allele of rs204999 contacts with cortical thickness in the left superior temporal.

Discussion

In summary, the present study provided evidence that single nucleotide polymorphisms(SNPs) on MHC relates with cortical thickness deficits in several regions.It is suggested that MHC, which plays a significant role in autoimmunity system, transform the structure or function of cells involved in immune response, the complement cascade, cytokines, heat shock proteins, transcription factors, other signaling molecules and olfactory receptors to give rise to changes in cortical thickness involving the frontal and temporal cortices 2,3. Here, our results further support the critical role of immune system in the pathology of schizophrenia via modulation the development of the cerebral cortical structure.

Conclusion:

The association of three SNPs on the major histocompatibility (MHC) with cortical thickness abnormalities in schizophrenia provided evidence that SNPs on MHC relate to the reduction of cortical thickness of the superior temporal gyrus in never treated SZ, which improve our understanding of the relationship between the abnormal genetic variants and gray matter deficits during the early course of illness. In the further study, longitudinal research with gray matter or white matter on a lager samples should be performed to confirm our findings and further investigate the trajectory of the disease.

Acknowledgements

No acknowledgement found.

References

1.Aiden Corvin , Derek W. Morris, et al.Genome-wide Association Studies: Findings at the Major Histocompatibility Complex Locus in Psychosis. BLOL PSYCHIATRY.2014;75:276-283.

2. Dominique Arion, Travis Unge, David A Lewis, Pat Levitt et al.Károly Mirnics,Molecular Evidence for Increased Expression of Genes Related to Immune and Chaperone Function in the Prefrontal Cortex in Schizophrenia.BIOL PSYCHIATRY.2007;62:711–721.

3. Katrina Radewicz , Laurence J. Garey, Stephen M. Gentleman , Richard Reynolds,et al. Increase in HLA-DR Immunoreactive Microglia in Frontal and Temporal Cortex of Chronic Schizophrenics.J Neuropathol Exp Neurol.2000;59:137-150.

Figures

Table 1. Correlation analyses between SNPs ON MHC and cortical thickness

Correlation is significant at the 0.05 level


Figure1. cortical thickness differences in SZ and healthy controls



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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