| 1 | GABAergic Abnormalities Associated with Sensorimotor Corticostriatal Community Structural Deficits in ErbB4 Knockout Mice and First-Episode Treatment-Naive Patients with Schizophrenia显示文摘The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients with schizophrenia.We used prepulse inhibition(PPI)and brain structural and diffusion MRI scans in 23 mice with conditional ErbB4 knockout in parvalbumin interneurons and 27 matched controls.Quantitative real-time PCR was used to assess the differential levels of GABA-related transcripts in brain regions.Concurrently,we measured structural and diffusion MRI and the cumulative contribution of risk alleles in the GABA pathway genes in firstepisode treatment-naı¨ve schizophrenic patients(n=117)and in age-and sex-matched healthy controls(n=86).We present the first evidence of gray and white matter impairment of right sensorimotor cortico-striatal networks and reproduced the sensorimotor gating deficit in a mouse model of schizophrenia.Significant correlations between gray matter volumes(GMVs)in the somatosensory cortex and PPI as well as glutamate decarboxylase 1 mRNA expression were found in controls but not in knockout mice.Furthermore,these findings were confirmed in a human sample in which we found significantly decreased gray and white matter in sensorimotor cortico-striatal networks in schizophrenic patients.The psychiatric risk alleles of the GABA pathway also displayed a significant negative correlation with the GMVs of the somatosensory cortex in patients.Our study identified that ErbB4 ablation in parvalbumin interneurons induced GABAergic dysregulation,providing valuable mechanistic insights into the sensorimotor cortico-striatal community structure deficits associated with schizophrenia. | Chengcheng Zhang Peiyan Ni Yikang Liu Yang Tian Jinxue Wei Bo Xiang Liansheng Zhao Xiaojing Li Xiaohong Ma Wei Deng Wanjun Guo Rongjun Ni Yamin Zhang Qiang Wang Hailiang Huang Nanyin Zhang Tao Li | 2020 | Neuroscience Bulletin2020，36，2： | 9 |
| 2 | Age-Related Reduction in Cortical Thickness in First-Episode Treatment-Na?ve Patients with Schizophrenia显示文摘Substantial evidence supports the neurodevelopmental hypothesis of schizophrenia.Meanwhile,progressive neurodegenerative processes have also been reported,leading to the hypothesis that neurodegeneration is a characteristic component in the neuropathology of schizophrenia.However,a major challenge for the neurodegenerative hypothesis is that antipsychotic drugs used by patients have profound impact on brain structures.To clarify this potential confounding factor,we measured the cortical thickness across the whole brain using highresolution T1-weighted magnetic resonance imaging in 145 first-episode and treatment-naive patients with schizophrenia and 147 healthy controls.The results showed that,in the patient group,the frontal,temporal,parietal,and cingulate gyri displayed a significant age-related reduction of cortical thickness.In the control group,age-related cortical thickness reduction was mostly located in the frontal,temporal,and cingulate gyri,albeit to a lesser extent.Importantly,relative to healthy controls,patients exhibited a significantly smaller age-related cortical thickness in the anterior cingulate,inferior temporal,and insular gyri in the right hemisphere.These results provide evidence supporting the existence of neurodegenerative processes in schizophrenia and suggest that these processes already occur in the early stage of the illness. | Yin Lin Mingli Li Yi Zhou Wei Deng Xiaohong Ma Qiang Wang Wanjun Guo Yinfei Li Lijun Jiang Xun Hu Nanyin Zhang Tao Li | 2019 | Neuroscience Bulletin2019，35，4： | 5 |
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