GRID1 thalamo-cortical gene variations absent in schizophrenia

Genetic variation in the glutamate receptor delta 1 gene (GRID1) affects gray matter of the anterior thalamus and left lateral prefrontal cortex in healthy individuals but not among patients with schizophrenia, suggest findings published in the Journal of Psychiatric Research.

According to Igor Nenadic (Jena University Hospital, Germany) and co-authors, the findings indicate an association of the schizophrenia candidate gene GRID1 with frontothalamic functioning.

"Our finding of a disease effect on anterior thalamus voxels contrasts with a genotype effect only in healthy controls but not patients, suggesting a differential effect related to either the expression of the schizophrenia disease phenotype or genetic liability," say the researchers.

Analysis of high-resolution magnetic resonance imaging data from 62 schizophrenia patients and 54 healthy controls using voxel-based morphometry found no effects of GRID1 genotype on total brain gray or white matter.

However, the rs3814614 homozygous risk genotype TT was associated with increased gray matter density in the anterior thalamus and the superior prefrontal and orbitofrontal cortex in healthy controls.

The researchers say that the presence of genotype effects in these brain areas in healthy individuals indicates that thalamocortical projects might be a circuitry affected by GRID1, or that gene products might influence structural integrity of these circuits.

By contrast, this association was not present among schizophrenia patients, in whom rs3814614 variation was associated with gray matter reductions in the medial parietal cortex and increases in the right medial cerebellum among homozygous TT individuals.

As suggested in previous studies, the absence of a genotype effect in schizophrenia patients could be a result of the GRID1 gene affecting other receptors and molecular pathways involved in schizophrenia pathology.

Nenadic and team also suggest that an effect on other gene products might explain the lack of genotype effect in schizophrenia patients: "Even though the T risk allele might be overrepresented in schizophrenia, it might not be sufficient on its own to interact in the emerging pathology leading to disease manifestation."

No significant genotype effects for white matter were seen in healthy controls, with only minor effects in the posterior temporal lobe seen among schizophrenia patients.

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