Cortical anatomical variations, gene expression profiles, and clinical phenotypes in patients with schizophrenia

Abstract

Background and hypothesis: Schizophrenia (SZ) patients display significant structural brain abnormalities; nevertheless, the genetic mechanisms regulating cortical anatomical variations and their correlation with the disease phenotype are still ambiguous.

Study design: We characterized anatomical variation using a surface-based method derived from structural magnetic resonance imaging of patients with SZ and age- and sex-matched healthy controls (HCs). Partial least-squares regression was performed across cortex regions between anatomical variation and average transcriptional profiles of SZ risk genes and all qualified genes from the Allen Human Brain Atlas. The morphological features of each brain region were correlated to symptomology variables in patients with SZ using partial correlation analysis.

Study results: A total of 203 SZ and 201 HCs were included in the final analysis. We observed significant variation of 55 regions of cortical thickness, 23 regions of volume, 7 regions of area, and 55 regions of local gyrification index (LGI) between SZ and HC groups. Expression profiles of 4 SZ risk genes and 96 genes from all qualified genes showed a correlation to anatomical variability, however, after multiple comparisons, the correlations were no longer significant. LGI variability in multiple frontal subregions was associated with specific symptoms of SZ, whereas cognitive function involving attention/vigilance was linked to LGI variability across nine brain regions.

Conclusions: Cortical anatomical variation of patients with schizophrenia is associated with gene transcriptome profiles as well as clinical phenotypes.

Keywords: Clinical phenotype; Gene expression; Magnetic resonance imaging; Morphology; Schizophrenia.