NCAM1 and neurocognition in schizophrenia

Background: Alterations in neurocognition may be fundamental to schizophrenia and may be endophenotypes. Neural cell adhesion molecule 1 (NCAM1, aliases NCAM and CD56) may be a candidate gene for schizophrenia or for neurocognition in schizophrenia as supported by linkage and functional findings. Methods: Subjects were 641 patients with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) clinical trial. Neurocognition was assessed at study baseline. Nine NCAM1 single nucleotide polymorphisms (SNPs) were blindly genotyped. Analysis of covariance was used to test for single SNP associations and haplotype regression for multilocus associations. Results: As there were suggestions of population stratification, all analyses were conducted stratified by inferred ancestry. In the Europe only stratum, there were nominally significant associations with five contiguous SNPs (rs1943620, rs1836796, rs1821693, rs686050, rs584427) with the strongest association at rs1836796 (p = .007). Via permutation testing, the probability of obtaining five consecutive statistically significant SNPs with p-values <= 5.05 was p = .0044. These results were robust to examination of model assumptions. Haplotype analyses did not identify significant haplotype associations. Conclusions: Although it is essential to see if these findings replicate in additional samples, we suggest that NCAM1 deserves further scrutiny for its relevance to clinical and etiological aspects of schizophrenia.