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.
