Methionine homozygosity at codon 129 in the prion protein is associated with white matter reduction and enlargement of CSF compartments in healthy volunteers and schizophrenic patients.

Twin studies point toward a substantial heritability in individual variations in the size of the human brain. However, the etiology is largely unknown. The prion protein (gene name: PRNP) aids cellular resistance to oxidative stress and neurodegeneration and is involved in neurodevelopment. This study examines the influence of a polymorphism in the PRNP gene on brain morphology in 47 healthy males and 43 male schizophrenic patients. All subjects underwent identical MRI scanning sessions followed by segmentation in cerebrospinal fluid (CSF), gray and white matter tissue, and genotyping for a biallelic polymorphism in PRNP (Met129Val). Genotype and allele frequencies did not differ between schizophrenic patients and controls but the polymorphism was associated with white matter tissue reduction (P = 0.024) and enlargement of CSF compartments (P = 0.039). These findings suggest that homozygosity for methionine at codon 129 is associated with decreased white matter tissue and larger CSF volume in right-handed male healthy volunteers and schizophrenic patients. This, however, being a novel finding, should warrant further investigation.