Neuregulin-1 genotypes and eye movements in schizophrenia

Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the neurocognitive processes that may involve NRG-1 in schizophrenia are unknown. Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes, which may be associated with brain dysfunctions underlying the pathophysiology of schizophrenia. The aim of this study was to investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia patients and healthy controls. Patients (N = 113) and controls (N = 106) were genotyped for two NRG-1 single nucleotide polymorphisms (SNPs); SNP8NRG222662, a surrogate marker for the originally described Icelandic NRG-1 risk haplotype, and SNP8NRG243177, which has recently been associated with individual differences in brain function. Subjects underwent infrared oculographic assessment of AS and SPEM. The study replicates previous findings of impaired AS and SPEM performance in schizophrenia patients (all P < 0.005; all d = 0.5-1.5). SNP8NRG243177 risk allele carriers had marginally increased variability of AS spatial error (P = 0.050, d = 0.3), but there were no significant genotype effects on other eye movement variables and no significant diagnosis-by-genotype interactions. Generally, risk allele carriers (G allele for SNP8NRG222662 and T allele for SNP8NRG243177) had numerically worse performance than non-carriers on most AS and SPEM variables. The results do not suggest that NRG-1 genotype significantly affects AS and SPEM task performance. However, the power of the sample to identify small effects is limited and the possibility of a type II error must be kept in mind. Larger samples may be needed to reliably investigate such gene effects on oculomotor endophenotypes.