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Brain Heterogeneity & Polygenic Risk in Schizophrenia

Schizophrenia is associated with substantial brain structural heterogeneity, possibly reflecting sensitivity to environmental and genetic perturbations in patients, a new study found. The case-control analysis included 1,151 patients and 2,010 controls. Researchers compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts, and tested for associations between polygenic risk score (PRS) and MRI features in a control cohort. Findings included:

  • Schizophrenia was associated with increased heterogeneity in frontotemporal thickness and area and cortical, ventricle, and hippocampal volumes, as well as reductions in mean estimates.
  • In an independent sample of 12,490 healthy controls, polygenic risk for schizophrenia was associated with thinner frontotemporal cortices and smaller CA2/3 volume of the left hippocampus, but not with dispersion.


Aln├Žs D, Kaufmann T, van der Meer D, et al. Brain heterogeneity in schizophrenia and its association with polygenic risk. [Published online ahead of print April 10, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0257.