Age-Related Reduction in Cortical Thickness in First-Episode Treatment-Naı¨ve Patients with Schizophrenia

Yin Lin 1,2,3 • Mingli Li 1,2 • Yi Zhou 4 • Wei Deng 1,2 • Xiaohong Ma 1,2 • Qiang Wang 1,2 • Wanjun Guo 1,2 • Yinfei Li 1,2 • Lijun Jiang 1,2 • Xun Hu 5 • Nanyin Zhang 6 • Tao Li 1,2

1Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China

2 West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China

3 Department of Psychology, Shenzhen Children’s Hospital, Shenzhen 518038, China

4 Department of Radiology, Hospital for Chengdu Office of Tibetan Autonomous Region, Branch Hospital of West China Hospital, Sichuan University, Chengdu 610041, China

5 Huaxi Biobank, West China Hospital, Sichuan University, Chengdu 610041, China

6 Department of Biomedical Engineering, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA


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 high-resolution T1-weighted magnetic resonance imaging in 145 first-episode and treatment-naïve 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.


Schizophrenia ; Cortical thickness; Age-related


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