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Social isolation and the brain: effects and mechanisms

Molecular Psychiatry volume 28, pages 191–201 (2023)Cite this article

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Abstract

An obvious consequence of the coronavirus disease (COVID-19) pandemic is the worldwide reduction in social interaction, which is associated with many adverse effects on health in humans from babies to adults. Although social development under normal or isolated environments has been studied since the 1940s, the mechanism underlying social isolation (SI)-induced brain dysfunction remains poorly understood, possibly due to the complexity of SI in humans and translational gaps in findings from animal models. Herein, we present a systematic review that focused on brain changes at the molecular, cellular, structural and functional levels induced by SI at different ages and in different animal models. SI studies in humans and animal models revealed common socioemotional and cognitive deficits caused by SI in early life and an increased occurrence of depression and anxiety induced by SI during later stages of life. Altered neurotransmission and neural circuitry as well as abnormal development and function of glial cells in specific brain regions may contribute to the abnormal emotions and behaviors induced by SI. We highlight distinct alterations in oligodendrocyte progenitor cell differentiation and oligodendrocyte maturation caused by SI in early life and later stages of life, respectively, which may affect neural circuit formation and function and result in diverse brain dysfunctions. To further bridge animal and human SI studies, we propose alternative animal models with brain structures and complex social behaviors similar to those of humans.

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Fig. 1: Overview of studies on social isolation.
Fig. 2
Fig. 3: Major brain regions and connectivities affected by early-life SI in humans and functional circuits in which these regions are involved.
Fig. 4: Effects of SI on oligodendrocyte progenitor cell (OPC) differentiation and oligodendrocyte (OL) maturation.

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Acknowledgements

We thank L. Zhu, M. Ho and W. Li for comments on the manuscript. We apologize for not citing all relevant references due to space limitations. We thank the two anonymous reviewers for comments and suggestions on the manuscript.

Funding

This work was supported by grants from The National Key Research and Development Program (2019YFA0707100 to YQZ and 2021ZD0203901 to YQZ and CL), the Strategic Priority Research Program B of the Chinese Academy of Sciences (XDBS1020100 to YQZ), and the National Science Foundation of China (31830036 and 31921002 to YQZ and 32171088 to CL).

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Authors and Affiliations

  1. State Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China

    Ying Xiong, Huilin Hong & Yong Q. Zhang

  2. Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China

    Cirong Liu

  3. Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, 201210, China

    Cirong Liu

  4. University of the Chinese Academy of Sciences, Beijing, 100101, China

    Yong Q. Zhang

Authors
  1. Ying Xiong
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  2. Huilin Hong
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  3. Cirong Liu
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  4. Yong Q. Zhang
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Contributions

YX: conceptualization, visualization, writing—original draft, writing—review and editing; HH: visualization, writing—original draft; CL: writing—review and editing; YQZ: conceptualization, writing—review and editing, supervision.

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Correspondence to Yong Q. Zhang.

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Xiong, Y., Hong, H., Liu, C. et al. Social isolation and the brain: effects and mechanisms. Mol Psychiatry 28, 191–201 (2023). https://doi.org/10.1038/s41380-022-01835-w

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