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

Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia.

Author information

  • 1Department of Bioengineering, National University of Singapore, Singapore.
  • 2Department of Bioengineering, National University of Singapore, Singapore ; Clinical Imaging Research Center, National University of Singapore, Singapore ; Singapore Institute for Clinical Sciences, the Agency for Science, Technology and Research, Singapore.
  • 3Research Division, Institute of Mental Health, Singapore.
  • 4Department of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Republic of Ireland.
  • 5Department of Neuroradiology, National Neuroscience Institute, Singapore.
  • 6Research Division, Institute of Mental Health, Singapore ; Department of General Psychiatry, Institute of Mental Health, Singapore.

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.

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