Subtypes of Insomnia Disorder Identified by Cortical Morphometric Similarity Network

Insomnia disorder (ID) is a highly heterogeneous psychiatric disease, and the use of neuroanatomical data to objectively define biological subtypes is essential. We aimed to examine the neuroanatomical subtypes of ID by morphometric similarity network (MSN) and the association between MSN changes and specific transcriptional expression patterns. We recruited 144 IDs and 124 healthy controls (HC). We performed heterogeneity through discriminant analysis (HYDRA) and identified subtypes within the MSN strength. Differences in MSN between subtypes and HC were compared, and clinical behavioral differences were compared between subtypes. In addition, we investigated the association between MSN changes and brain gene expression in different ID subtypes using partial least squares regression to assess genetic commonalities in psychiatric disorders and further performed functional enrichment analyses. Two distinct subtypes of ID were identified, each exhibiting different MSN changes compared to HC. Furthermore, subtype 1 is characterized by objective short sleep, impaired cognitive function, and some relationships with major depressive disorder and autism spectrum disorder (ASD). In contrast, subtype 2 has normal objective sleep duration but subjectively reports poor sleep and is only related to ASD. The pathogenesis of subtype 1 may be related to genes that regulate sleep rhythms and sleep-wake cycles. In contrast, subtype 2 is more due to adverse emotion perception and regulation. Overall, these findings provide insights into the neuroanatomical subtypes of ID, elucidating the relationships between structural and molecular aspects of the relevant subtypes.