A risk PRODH haplotype affects sensorimotor gating, memory, schizotypy, and anxiety in healthy male subjects.
BACKGROUND
Significant associations have been shown for haplotypes comprising three PRODH single nucleotide polymorphisms (SNPs; 1945T/C, 1766A/G, 1852G/A) located in the 3' region of the gene, suggesting a role of these variants in the etiopathogenesis of schizophrenia. We assessed the relationship between these high-risk PRODH polymorphisms and schizophrenia-related endophenotypes in a large and highly homogeneous cohort of healthy males.


METHODS
Participants (n = 217) were tested in prepulse inhibition (PPI), verbal and working memory, trait anxiety and schizotypy. The QTPHASE from the UNPHASED package was used for the association analysis of each SNP or haplotype data. This procedure revealed significant phenotypic impact of the risk CGA haplotype. Subjects were then divided in two groups; levels of PPI, anxiety, and schizotypy, verbal and working memory were compared with analysis of variance.


RESULTS
CGA carriers (n = 32) exhibited attenuated PPI (p < .001) and verbal memory (p < .001) and higher anxiety (p < .004) and schizotypy (p < .008) compared with the noncarriers (n = 185). There were no differences in baseline startle, demographics, and working memory. The main significant correlations were schizotypy x PPI [85-dB, 120-msec trials] in the carriers and schizotypy x anxiety in the entire group and the noncarriers but not the carriers group.


CONCLUSIONS
Our results strongly support PPI as a valid schizophrenia endophenotype and highlight the importance of examining the role of risk haplotypes on multiple endophenotypes and have implications for understanding the continuum from normality to psychosis, transitional states, and the genetics of schizophrenia-related traits.
Roussos
Panos
P
Department of Psychiatry and Behavioral Sciences, University of Crete, Heraklion, Greece. roussosp@edu.med.uoc.gr
Giakoumaki
Stella G
SG
Bitsios
Panos
P
D000328:Adult; D001007:Anxiety / Q000235:genetics* / Q000523:psychology*; D015331:Cohort Studies; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term; D011394:Proline Oxidase / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics*; D012569:Schizotypal Personality Disorder / Q000235:genetics* / Q000523:psychology*; D011795:Surveys and Questionnaires; D014706:Verbal Learning
D011394:Proline Oxidase