title: M129V variation in the prion protein gene and psychotic disorders: relationship to neuropsychological and psychopathological measures.
abstract: The methionine/valine polymorphism at position 129 in the prion protein gene, PRNP M129V, is a known risk factor for Creutzfeldt-Jakob disease (CJD). Psychiatric manifestations including psychosis are common in the early phase of CJD and it has therefore been hypothesized that the prion protein could be involved in psychotic disorders. Moreover, among the various hypothesized functions of the prion protein, a role in synaptic activity has been described. We have studied the PRNP M129V variant with regard to psychotic disorders from two perspectives: first as a genetic risk factor and second as a genetic factor influencing phenotypic variation. A case-control study of 482 psychotic patients and 502 controls indicated that differences between patients and controls were not present in genotype distributions or allele frequencies. We also studied the influence of this variant in psychopathological symptomatology and neuropsychological performance in a subgroup of 159 psychotic patients. In our sample, patients homozygous for valine at this position presented less severe scores in the general psychopathological subscale (p=0.003) and in the sum of the total items (p=0.007) of the Positive and Negative Syndrome Scale (PANSS). Also, homozygote VV patients presented better scores in most neuropsychological tests, the most significant result of which was for delayed visual memory (p=0.021). In summary, our results do not support the hypothesis that M129V is a susceptibility factor for psychotic disorders. However, it could influence their phenotypic variation at the psychopathological and neuropsychological level. Independent replications are needed to confirm that being homozygotic for valine at PRNP M129V position is associated with better psychopathological and neuropsychological scores in psychotic disorders.
authors.affiliation: Departament de Formació i Investigació, Hospital Psiquiàtric Universitari Institut Pere Mata, Reus, Spain. lourdes.martorell@urv.cat
authors.forename: Lourdes
authors.initials: L
authors.lastname: Martorell
authors.forename: Joaquín
authors.initials: J
authors.lastname: Valero
authors.forename: Begoña
authors.initials: B
authors.lastname: Mulet
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gutiérrez-Zotes
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Cortés
authors.forename: Manel
authors.initials: M
authors.lastname: Jariod
authors.forename: Modesto
authors.initials: M
authors.lastname: Pérez
authors.forename: Antonio
authors.initials: A
authors.lastname: Labad
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D014633:Valine / Q000235:genetics*; D014888:Wechsler Scales
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D008715:Methionine; D014633:Valine