Aberrant Hippocampal Development in Early‑onset Mental Disorders and Promising Interventions:Evidence from a Translational Study  

作　　者：Jingyu Yang Huiling Guo Aoling Cai Junjie Zheng Juan Liu Yao Xiao Sihua Ren Dandan Sun Jia Duan Tongtong Zhao Jingwei Tang Xizhe Zhang Rongxin Zhu Jie Wang Fei Wang 

机构地区：[1]Early Intervention Unit,Department of Psychiatry,Affiliated Nanjing Brain Hospital,Nanjing Medical University,Nanjing 210029,China [2]School of Biomedical Engineering and Informatics,Nanjing,Medical University,Nanjing 211166,China [3]The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University,Changzhou Second People’s Hospital,Changzhou Medical Center,Nanjing Medical University,Changzhou 213004,China [4]Department of Radiology,First Hospital of China Medical University,Shenyang 110002,China [5]Department of Cardiac Function,The People’s Hospital of China Medical University and the People’s Hospital of Liaoning Province,Shenyang 110067,China [6]Key Laboratory of Magnetic Resonance in Biological Systems,State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics,National Center for Magnetic Resonance in Wuhan,Wuhan Institute of Physics and Mathematics,Innovation Academy for Precision Measurement Science and Technology,Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics,Wuhan 430064,China [7]Institute of Neuroscience and Brain Diseases,Xiangyang Central Hospital,Affiliated Hospital of Hubei University of Arts and Science,Xiangyang 441021,China [8]Functional Brain Imaging Institute of Nanjing Medical University,Nanjing 210029,China

出　　处：《Neuroscience Bulletin》2024年第6期683-694,共12页神经科学通报（英文版）

基　　金：supported by the National Science Fund for Distinguished Young Scholars(81725005);the National Natural Science Foundation Regional Innovation and Development Joint Fund(U20A6005);the National Natural Science Foundation of China(82151315 and 62176129);the National Key Research and Development Program(2022YFC2405605);the Jiangsu Provincial Key Research and Development Program(BE2021617 and BE2022160);the Key Project supported by Medical Science and Technology Development Foundation,Jiangsu Commission of Health(ZD2021026);the Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB818);the Postdoctoral Research Project of Changzhou Medical Center,Nanjing Medical University(CMCP202305).

摘　　要：Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence.The methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective.We conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for intervention.Then,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was investigated.In addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational potential.The results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all P<0.001).In contrast,the volume of the hippocampus did not show significant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both P<0.001).Subsequently,rTMS was applied to the occipital cortex,which is anatomically connected to the hippocampus,in the MAM models during adolescence.The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(P<0.01),while the volume of the striatum remained unchanged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(P<0.01),and these volumetric changes were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for earlyonset mental disorders with neuro

关 键 词：EARLY-ONSET Mental disorder NEURODEVELOPMENT Animal model Hippocampus Repetitive transcranial magnetic stimulation 

分 类 号：R749.16[医药卫生—神经病学与精神病学]