DEVELOPMENTAL GENETIC ASPECTS OF SCHIZOPHRENIA, NEUREGULIN-1, AND COGNITION

Recent work suggests potentially promising relationships between sequence variation in Neuregulin-1 (NRG1) and both schizophrenia and neurocognitive function. Cognitive deficits are very common in schizophrenia and have been shown to be familial in nature. Based on these findings, we hypothesized that cognitive deficits may be related to variation in NRG1 in an age-dependent manner during adolescence and adulthood, thus providing a possible mechanism by which NRG1 could act as a late neurodevelopmental susceptibility gene for schizophrenia.\ud \ud This question was examined using individuals from 39 multigenerational multiplex families, including 58 affected participants and 361 unaffected relatives aged 15-85 years. Participants were genotyped for 36 NRG1 single nucleotide polymorphisms (SNPs) previously associated with schizophrenia. Participants completed diagnostic interviews and a computerized neurocognitive battery that assessed eight cognitive domains.\ud \ud Pedigree-based variance component analyses were performed to estimate the main effects of age and individual SNPs, and the interactions between age and SNPs in predicting cognition for each domain. There were multiple nominally significant NRG1 x age interactions across several domains and markers, although few remained significant after modified Bonferroni correction. Overall, this study suggests a potential role of NRG1 x age interactions in cognitive performance within multiplex families with schizophrenia, especially within the domains of Emotional Processing, Abstraction/Mental Flexibility, Attention, and Sensorimotor Dexterity and the NRG1 markers SNP8NRG221132, SNP8NRG221533/rs35753505, rs776401, and rs1473438 that warrants further investigation