TY - JOUR
T1 - A Risk PRODH Haplotype Affects Sensorimotor Gating, Memory, Schizotypy, and Anxiety in Healthy Male Subjects
AU - Roussos, Panos
AU - Giakoumaki, Stella G.
AU - Bitsios, Panos
N1 - Funding Information:
This project was supported by the University of Crete Research Funds Account (E.L.K.E. 1348). PR was supported by a Manasaki scholarship, and SGG was supported by a Propondis Foundation postdoctorate fellowship.
PY - 2009/6/15
Y1 - 2009/6/15
N2 - 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 × PPI [85-dB, 120-msec trials] in the carriers and schizotypy × 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.
AB - 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 × PPI [85-dB, 120-msec trials] in the carriers and schizotypy × 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.
KW - PRODH
KW - Prepulse inhibition
KW - schizotypy
KW - trait anxiety
KW - verbal memory
KW - working memory
UR - http://www.scopus.com/inward/record.url?scp=67349160223&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2009.01.003
DO - 10.1016/j.biopsych.2009.01.003
M3 - Article
C2 - 19232576
AN - SCOPUS:67349160223
SN - 0006-3223
VL - 65
SP - 1063
EP - 1070
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 12
ER -