Brain network simulations indicate effect of neuregulin-1 genotype on excitation-inhibition balance in cortical dynamics

Introduction Previous research indicates that patients with schizophrenia exhibit alterations in brain structure, brain function and neurochemistry. The high heritability of the disorder suggests that genetic factors play an important role in this pathophysiology. However, the specific factors driving the observed brain alterations remain unclear. Previous research indicates that single-nucleotide polymorphisms (SNPs) in the Neuregulin-1 (NRG1) gene could affect brain structure or brain function. Moreover, animal research suggests that NRG1 is a moderator of the excitatory-inhibitory (E – I) balance in cortical circuits with subsequent effects on cognition and potential relevance for the cognitive deficits observed in patients with schizophrenia.

Methods and Results For rs3924999 our results indicate that G-homozygotes exhibit effective connectivity in brain activity characterized by significantly lower local excitatory recurrence (p = 0.038) and significantly higher excitatory synaptic coupling (p = 0.033). Network-based statistics indicate no significant differences in structural connectivity between these groups, suggesting that these findings do not result from NRG1 effects on brain structural connectivity. There are no significant effects for the SNP rs35753505 (all p > 0.05).

Conclusion Our results suggest that NRG1 might be related to alterations in E – I balance in cortical circuits emphasizing the potential relevance of this genetic factor for the pathophysiology of schizophrenia. Moreover, we suggest the integration of imaging-genetics approaches with computational models of the brain, might be a promising way to investigate specific neurobiological pathways in psychiatric disorders.

 

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