Grey matter changes associated with host genetic variation and exposure to Herpes Simplex Virus 1 (HSV1) in first episode schizophrenia

SCHIZOPHRENIA RESEARCH

卷:118

Article

Prasad, Konasale M.¹  Bamne, Mikhil N.¹  Shirts, Brian H.²  Goradia, Dhruman¹  Mannali, Vimal¹  Pancholi, Krishna M.¹  Xue, Bai¹  McClain, Lora¹  Yolken, Robert H.³  Keshavan, Matcheri S.^1,4  Nimgaonkar, Vishwajit L.¹ 

[1] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA

[2] Univ Utah, Sch Med, Salt Lake City, UT USA

[3] Johns Hopkins Sch Med, Stanley Div Dev Neurovirol, Baltimore, MD USA

[4] Harvard Univ, Sch Med, Boston, MA USA

关键词: Schizophrenia;    Herpes Simplex Virus;    MICB;    Immune genes;    Cognition;    Neuroanatomy;    Neuroimaging;    Morphometry;   

DOI  :  10.1016/j.schres.2010.01.007

来源: Elsevier

【 摘 要 】

Background: We previously reported reduced prefrontal cortex (PFC) grey matter volume among first episode, antipsychotic-naive schizophrenia subjects (SZ) exposed to HSV1 but not among healthy subjects (HS) (Prasad et al., 2007). Independently, rs1051788, an exonic polymorphism of the MHC Class 1 polypeptide-related sequence B (MICB) gene was associated with HSV1 seropositivity, as well as SZ risk. In this study, we examined whether PFC grey matter changes associated with HSV1 exposure varied against the background of MICB genotypes. Methods: We examined Caucasian individuals from the sample we studied in our previous report (Prasad et al., 2007) (SZ, n=21 and HS, n=19). Whole brain voxelwise analysis of structural MRI scans was conducted using Statistical Parametric Mapping, vet 5 (SPM5). The impact of rs1051788 variation and HSV1 seropositivity on grey matter volumes was examined using regression models on the combined sample of cases and controls, and then within each diagnostic group. Results: In the combined sample of cases and controls, we observed the main effects of HSV1 seropositivity and genotypes, and a significant joint effect of HSV1 seropositivity and genotype mainly in the PFC. The joint effect was more prominent among cases than among controls. Discussion: Our observations suggest that rs1051788 and HSV1 seropositivity are associated individually and jointly with reduced PFC grey matter volume. The patterns of these associations differ by diagnostic status, and these factors explain only a small portion of the variance in the grey matter volume reductions. (C) 2010 Elsevier B.V. All rights reserved.

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