Genetic Variation in the Schizophrenia-Risk Gene Neuregulin I Correlates with Brain Activation and Impaired Speech Production in a Verbal Fluency Task in Healthy Individuals

Impaired performance in verbal fluency tasks is an often replicated finding in schizophrenia. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and temporal areas. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes for the disorder, such as NRG1, modulate verbal fluency performance and its neural correlates. Four hundred twenty-nine healthy individuals performed a semantic and a lexical verbal fluency task. A subsample of 85 subjects performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (MRI). NRGI (SNP8NRG221533; rs35753505) status was determined and correlated with verbal fluency performance and brain activation. For the behavioral measure, there was a linear effect of NRG1 status on semantic but not on lexical verbal fluency. Performance decreased with number of risk-alleles. In the fMRI experiment, decreased activation in the left inferior frontal and the right middle temporal gyri as well as the anterior cingulate gyrus was correlated with the number of risk-alleles in the semantic verbal fluency task. NRG1 genotype does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in schizophrenia and may explain some of the cognitive and brain activation variation found in the disorder. More generally, NRG1 might be one of several genes that influence semantic language capacities.