Psychotic disorders have a lifetime prevalence of up to three percent and can be extremely debilitating
However, despite significant efforts, the brain architectural changes and biological mechanisms causing psychotic disorders are not yet well understood, and there has been correspondingly limited progress in the development of new therapeutics.
New research by Dr Sarah Morgan looks at the cortical patterning of abnormal morphometric similarity in psychosis and shows that it is associated with brain expression of schizophrenia-related genes.
Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics.
Using morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case-control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies.
There was also a replicable pattern of case-control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex.
Using prior brain-wide gene expression data, we found that the cortical map of case-control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms and pathways.
In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia.
Combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins, as well as a number of unreported genes in their topological vicinity on the protein interaction network, may drive structural brain network changes mediating the genetic risk of schizophrenia.
Image credit @jesseo81