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.
Highlights
Schizophrenia is a heterogeneous psychiatric disorder with a complex etiology
Risk T-allele homozygote genotype was associated with thalamic shape abnormalities involving regions related to pulvinar and medial dorsal nucleus in patients with schizophrenia compared to controls
Our findings of cortical thinning involving frontal, temporal and parietal cortices are consistent with cortical thickness changes which have been previously reported in schizophrenia at different phases of illness including first episode cases [22,23] as well as in those with chronic illness [24]
Summary
There is a strong genetic component involved in the pathogenesis of schizophrenia. In recent years multiple genetic markers have been identified as conferring increased risk for schizophrenia from genome wide association studies [1,2]. One of these markers is the rs12807809 (T/C) single nucleotide polymorphism (SNP) in the neurogranin (NRGN) gene [2]. The NRGN protein is a postsynaptic protein that is expressed in the human brain and involved in the regulation of calmodulin availability in neurons [4,5]. NRGN has been implicated with important roles in synaptic signaling, plasticity, neural development, learning and memory [6,7]
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