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


CONCLUSIONS
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.
Prasad
Konasale M
KM
University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States. Prasadkm@upmc.edu
Bamne
Mikhil N
MN
Shirts
Brian H
BH
Goradia
Dhruman
D
Mannali
Vimal
V
Pancholi
Krishna M
KM
Xue
Bai
B
McClain
Lora
L
Yolken
Robert H
RH
Keshavan
Matcheri S
MS
Nimgaonkar
Vishwajit L
VL
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D018259:Herpesvirus 1, Human / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000473:pathology / Q000821:virology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology / Q000821:virology; D055815:Young Adult
D015395:Histocompatibility Antigens Class I; C098080:MICB antigen