Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia

PLoS One. 2013 Dec 30;8(12):e85603. doi: 10.1371/journal.pone.0085603. eCollection 2013.

Abstract

Although the genome wide supported psychosis susceptibility neurogranin (NRGN) gene is expressed in human brains, it is unclear how it impacts brain morphology in schizophrenia. We investigated the influence of NRGN rs12807809 on cortical thickness, subcortical volumes and shapes in patients with schizophrenia. One hundred and fifty six subjects (91 patients with schizophrenia and 65 healthy controls) underwent structural MRI scans and their blood samples were genotyped. A brain mapping algorithm, large deformation diffeomorphic metric mapping, was used to perform group analysis of subcortical shapes and cortical thickness. Patients with risk TT genotype were associated with widespread cortical thinning involving frontal, parietal and temporal cortices compared with controls with TT genotype. No volumetric difference in subcortical structures (hippocampus, thalamus, amygdala, basal ganglia) was observed between risk TT genotype in patients and controls. However, patients with risk TT genotype were associated with thalamic shape abnormalities involving regions related to pulvinar and medial dorsal nuclei. Our results revealed the influence of the NRGN gene on thalamocortical morphology in schizophrenia involving widespread cortical thinning and thalamic shape abnormalities. These findings help to clarify underlying NRGN mediated pathophysiological mechanisms involving cortical-subcortical brain networks in schizophrenia.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / metabolism
  • Female
  • Genotype*
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Neurogranin / genetics*
  • Neurogranin / metabolism
  • Radiography
  • Schizophrenia / diagnostic imaging*
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Thalamus / diagnostic imaging*
  • Thalamus / metabolism

Substances

  • NRGN protein, human
  • Neurogranin

Grants and funding

This work is supported by the Young Investigator Award at National University of Singapore (NUSYIA FY10 P07, AQ), National University of Singapore MOE AcRF Tier 1 (AQ), National Healthcare Group SIG Grant NHG-SIG/05004 (KS) and ASTAR/Singapore Biomedical Imaging Consortium Grant SBIC RP C-009/2006 (KS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.