Progressive gray matter hypertrophy with severity stages of insomnia disorder and its relevance for mood symptoms



To investigate the gray matter (GM) alterations in patients with insomnia disorder (ID) at different severity stages and the relationship between GM alterations and sleep, mood, and cognitive measures.


One hundred one ID patients and 63 healthy controls (HC) were included. Each patient underwent structural MRI and completed sleep-, mood-, and cognitive-related questionnaires. The ID patients were further grouped into subthreshold insomnia (SI) group and clinical insomnia (CI) group. We investigated changes in GM volumes in ID patients via diffeomorphic anatomical registration through exponentiated lie algebra voxel-based morphometry (DARTEL-VBM). We first compared voxel-wise differences in GM volumes between the HC group and the ID group. Analysis of variance was performed on individual GM maps in the SI, CI, and HC groups to further investigate the effects of different stages of ID severity on GM volumes. Multiple regression was used to model the relationship between altered GM volumes in SI and CI groups and clinical measures.


GM hypertrophies in the left anterior and middle cingulate gyrus, right middle and inferior temporal gyrus, and right cerebellum Crus II were detected in ID. Increased GM volume in the right middle temporal gyrus was detected in the SI group, whereas all three regions in the CI group. Regression analysis showed that mood- and cognitive-related measures had a positive correlation with GM volumes, while sleep-related measures had a negative correlation with GM volumes in the CI group.


Our findings of the progressively increased GM volumes in ID suggest that a hypertrophic cortical morphological mechanism may underlie the altered neuroanatomy induced by insomnia.

Key Points

Insomnia-induced GM hypertrophies in the cingulate gyrus, temporal gyrus, and cerebellum Crus II.

The middle temporal gyrus was early detectable in the SI group.

The increased GM volumes in the CI group were correlated with clinical measures.

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Anterior cingulate cortex


Clinical insomnia


Diffeomorphic anatomical registration through exponentiated lie algebra


Gray matter


Healthy controls


Insomnia disorder


Major depressive disorder


Subthreshold insomnia


Voxel-based morphometry


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We would like to thank all the participants involved in this project.


This study was funded by the National Natural Science Foundation of China (Grant Nos. 81901731, 81701111, 81471639, U1903120, 81771807), the Science and Technology Planning Project of Guangdong (202002030234), and the National Natural Science Foundation of Guangdong Province (2018A0303130129)

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Corresponding author

Correspondence to Guihua Jiang.

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The scientific guarantor of this publication is Guihua Jiang.

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The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Bin A. Wang has significant statistical expertise.

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Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.


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Li, S., Wang, B.A., Li, C. et al. Progressive gray matter hypertrophy with severity stages of insomnia disorder and its relevance for mood symptoms. Eur Radiol (2021).

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  • Insomnia disorder
  • Gray matter
  • Hypertrophy
  • Mood