TY - JOUR
T1 - Grey matter changes associated with host genetic variation and exposure to Herpes Simplex Virus 1 (HSV1) in first episode schizophrenia
AU - Prasad, Konasale M.
AU - Bamne, Mikhil N.
AU - Shirts, Brian H.
AU - Goradia, Dhruman
AU - Mannali, Vimal
AU - Pancholi, Krishna M.
AU - Xue, Bai
AU - McClain, Lora
AU - Yolken, Robert H.
AU - Keshavan, Matcheri S.
AU - Nimgaonkar, Vishwajit L.
N1 - Funding Information:
This work was supported by grants from the National Institute of Mental Health MH72995 (KMRP), MH63420, 66263, 56242 and Stanley Foundation (VLN) and MH45156 (MSK). The funding agencies did not have any further role in the design or execution of the study, analyses, interpretation of results and preparation of the manuscript.
PY - 2010/5
Y1 - 2010/5
N2 - Background: We previously reported reduced prefrontal cortex (PFC) grey matter volume among first episode, antipsychotic-naïve 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 I 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, ver 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.
AB - Background: We previously reported reduced prefrontal cortex (PFC) grey matter volume among first episode, antipsychotic-naïve 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 I 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, ver 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.
KW - Cognition
KW - Herpes Simplex Virus
KW - Immune genes
KW - MICB
KW - Morphometry
KW - Neuroanatomy
KW - Neuroimaging
KW - Schizophrenia
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U2 - 10.1016/j.schres.2010.01.007
DO - 10.1016/j.schres.2010.01.007
M3 - Article
C2 - 20138739
AN - SCOPUS:77951978940
SN - 0920-9964
VL - 118
SP - 232
EP - 239
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -