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In vivo study sheds new light on the dendritic spine pathology hypothesis of schizophrenia

Molecular Psychiatry volume 27, pages 1866–1868 (2022)Cite this article

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To date, the neuropathophysiology of schizophrenia has yet to be fully elucidated. Although structural brain abnormalities (including the reduced gray matter of some brain regions and hippocampus) have been frequently reported in schizophrenia [1,2,3], it is unclear whether these abnormalities represent intrinsic characteristics or are due to the effects of antipsychotics and illness progression. In addition, these abnormalities are typically subtle, lack regional specificity, and are difficult to replicate in most schizophrenia cases. Moreover, recent studies showed no evidence of genetic overlap between subcortical volume measurements and schizophrenia risk [4, 5], indicating that structural brain abnormalities may not be a typical neuropathological feature of schizophrenia.

In the process of describing the neuropathology of schizophrenia, reductions in dendritic spine density have been frequently reported [6,7,8,9,10,11,12]. Dendritic spines are small membranous protrusions located on the dendritic processes of neurons. As a major anatomical unit for memory storage and synaptic transmission, dendritic spines usually receive excitatory input from axons, and most excitatory synaptic transmission occurs in dendritic spines. Dendritic spine formation is a dynamic process, and the structural plasticity of dendritic spines plays pivotal roles in learning, memory, and other cognitive processes. In 2000, Glantz et al. reported decreased dendritic spine density of prefrontal cortical pyramidal neurons in schizophrenia [6]. Subsequently, decreased dendritic spine density in schizophrenia was repeatedly reported [7, 10, 13, 14]. These consistent neuropathological findings (i.e., decreased dendritic spine density in schizophrenia) support the dendritic spine pathology of schizophrenia [7,8,9, 15, 16].

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Acknowledgements

This study was equally supported by the Key Research Project of Yunnan Province (202101AS070055) and the National Nature Science Foundation of China (U2102205). In addition, the study was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDPB17), the Major Science and Technology Projects of Henan Province (201300310200 to X-JL), the Distinguished Young Scientists Grant of Yunnan Province (202001AV070006), the Innovative Research Team of Science and Technology Department of Yunnan Province (2019HC004), the Western Light Innovative Research Team of Chinese’s Academy of Sciences, and the National Nature Science Foundation of China (81971252, U1904130, 31970561, 82171498).

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Authors and Affiliations

  1. Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, China

    Wenqiang Li & Luxian Lv

  2. Henan Key Lab of Biological Psychiatry, International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang Medical University, Xinxiang, Henan, 453002, China

    Wenqiang Li & Luxian Lv

  3. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650204, China

    Xiong-Jian Luo

  4. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China

    Xiong-Jian Luo

  5. Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan, 650204, China

    Xiong-Jian Luo

  6. KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650204, China

    Xiong-Jian Luo

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X-JL, WQL, and LXL wrote the manuscript. All authors revised the manuscript critically and approved the final version.

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Correspondence to Xiong-Jian Luo.

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Li, W., Lv, L. & Luo, XJ. In vivo study sheds new light on the dendritic spine pathology hypothesis of schizophrenia. Mol Psychiatry 27, 1866–1868 (2022). https://doi.org/10.1038/s41380-022-01449-2

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