Genetic variation in neuregulin1 is associated with differences in prefrontal engagement in children

The majority of psychopathology is rooted early in life and first emerges during childhood and adolescence. However, little is known about how risk genes affect brain function to increase biological vulnerability to psychopathology in childhood, because most imaging genetic studies published so far have been conducted on adult participants. We examined the impact of neuregulin1 (NRG1), a probable susceptibility gene for schizophrenia and bipolar disorder, on brain function in a sample of 102 ten- to twelve-year-old children. Each participant performed a Go/Nogo task, whereas brain responses were measured using functional magnetic resonance imaging. Statistical parametric mapping was used to estimate the impact of genetic variation in NRG1 on brain activation. Response accuracy and reaction times did not differ as a function of NRG1 genotype. However, individuals with the high-risk variant expressed greater brain activation for both Go and Nogo stimuli in the right posterior orbital gyrus, where NRG1 genotype accounted for 11% of interindividual variance. There were no regions showing a significant interaction between NRG1 genotype and stimulus type even at trend level, suggesting that the impact of NRG1 on brain activation was not specific to either response inhibition or motor execution. These results suggest that that genetic variation in NRG1 is associated with different levels of prefrontal engagement in children as young as 10-12 years of age. Our investigation provides support to the idea that genetic factors may affect brain function to moderate vulnerability to psychopathology from childhood.