Meiling Li1,2, Benjamin Becker1,2, Junjie Zheng1,2, Yan Zhang3, Heng Chen1,2, Wei Liao1,2, Xujun Duan1,2, Hesheng Liu4, Jingping Zhao5, Huafu Chen1,2. 1. The Clinical Hospital of Chengdu Brain Science Institute, Ministry of Education Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China. 2. School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China. 3. Department of Psychiatry, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. 4. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA. 5. Institute of Mental Health, the Second Xiangya Hospital, Central South University, Changsha, China.
Abstract
BACKGROUND: Schizophrenia has been conceptualized as a brain network disorder rooted in dysregulated neurodevelopmental processes. Recent neuroimaging studies revealed disrupted brain connectomic organization in adult schizophrenia patients. However, altered developmental trajectories of the functional connectome during the adolescent maturational stage have not been examined. METHODS: The present study combined functional MRI with a graph theoretical approach to examine functional network topology and its age-related development in 39 medication naïve, first-episode patients with adolescent-onset schizophrenia and 31 matched controls (age range: 12-18 years). RESULTS: Patients demonstrated impaired large-scale integration as reflected by reduced global efficiency as well as decreased regional nodal efficiency in highly integrative network hubs, most consistently the hippocampal formation and the precuneus. Furthermore, the left hippocampus showed opposite age-efficiency associations in healthy controls and patients, indicating dysregulated maturational trajectories in adolescent schizophrenia and a particular vulnerability of this region during early pathological attack. CONCLUSIONS: The findings allow an integrative perspective on network and neurodevelopmental perspectives on schizophrenia, suggesting that dysregulated maturation of the functional connectome during adolescence might reflect an early marker for the disorder.
BACKGROUND:Schizophrenia has been conceptualized as a brain network disorder rooted in dysregulated neurodevelopmental processes. Recent neuroimaging studies revealed disrupted brain connectomic organization in adult schizophreniapatients. However, altered developmental trajectories of the functional connectome during the adolescent maturational stage have not been examined. METHODS: The present study combined functional MRI with a graph theoretical approach to examine functional network topology and its age-related development in 39 medication naïve, first-episode patients with adolescent-onset schizophrenia and 31 matched controls (age range: 12-18 years). RESULTS:Patients demonstrated impaired large-scale integration as reflected by reduced global efficiency as well as decreased regional nodal efficiency in highly integrative network hubs, most consistently the hippocampal formation and the precuneus. Furthermore, the left hippocampus showed opposite age-efficiency associations in healthy controls and patients, indicating dysregulated maturational trajectories in adolescent schizophrenia and a particular vulnerability of this region during early pathological attack. CONCLUSIONS: The findings allow an integrative perspective on network and neurodevelopmental perspectives on schizophrenia, suggesting that dysregulated maturation of the functional connectome during adolescence might reflect an early marker for the disorder.
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