Thong Jamie Yu Jin, Qiu Anqi, Sum Min Yi, Kuswanto Carissa Nadia, Tuan Ta Ahn, Donohoe Gary, Sitoh Yih Yian, Sim Kang
Department of Bioengineering, National University of Singapore, Singapore.
Department 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.
PLoS One. 2013 Dec 30;8(12):e85603. doi: 10.1371/journal.pone.0085603. eCollection 2013.
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.
尽管全基因组支持的精神病易感性神经颗粒素(NRGN)基因在人类大脑中表达,但尚不清楚它如何影响精神分裂症患者的脑形态。我们研究了NRGN rs12807809对精神分裂症患者皮质厚度、皮质下体积和形状的影响。156名受试者(91名精神分裂症患者和65名健康对照)接受了结构磁共振成像扫描,并对他们的血样进行了基因分型。使用一种脑图谱算法——大变形微分同胚度量映射,对皮质下形状和皮质厚度进行组间分析。与TT基因型的对照相比,具有风险TT基因型的患者存在广泛的皮质变薄,累及额叶、顶叶和颞叶皮质。在患者和对照的风险TT基因型之间,未观察到皮质下结构(海马体、丘脑、杏仁核、基底神经节)的体积差异。然而,具有风险TT基因型的患者与涉及丘脑枕和背内侧核相关区域的丘脑形状异常有关。我们的结果揭示了NRGN基因对精神分裂症丘脑皮质形态的影响,包括广泛的皮质变薄和丘脑形状异常。这些发现有助于阐明NRGN介导的涉及精神分裂症皮质-皮质下脑网络的病理生理机制。