Sequencing of five left-right cerebral asymmetry genes in a cohort of schizophrenia and schizotypal disorder patients from Russia.

Objective: Schizophrenia is a severe psychiatric disorder, affecting ∼1% of the human population. The genetic contribution to schizophrenia is significant, but the genetics are complex and many aspects of brain functioning, from neural development to synapse structure, seem to be involved in the pathogenesis. A novel way to study the molecular causes of schizophrenia is to study the genetics of left-right (LR) brain asymmetry, the disease feature often observed in schizophrenic patients.

Methods: In this study, we analyzed by sequencing five candidate LR cerebral asymmetry genes in a cohort of 95 schizophrenia and schizotypal disorder patients from Saint Petersburg, Russia. The gene list included LMO4, LRRTM1, FOXP2, the PCDH11X/Y gene pair, and SRY.

Results: We found 17 previously unreported variants in the genes LRRTM1, FOXP2, LMO4, and PCDH11X in the 3'-UTR and 5'-UTR. The variants might contribute toward an altered mRNA processing, which could lead to altered mRNA amounts in developing neurons of the brain and establishment of an incorrect LR asymmetry profile.

Conclusion: This is the first study in which multiple candidate genes for cerebral LR asymmetry and schizophrenia have been analyzed by sequencing. The approach to study the genetics of schizophrenia from the perspective of an LR cerebral asymmetry disturbance deserves more attention.