Lack of Structural Brain Alterations associated with Insomnia: Findings from the ENIGMA-Sleep working group

Existing neuroimaging studies have reported divergent structural alterations in insomnia. Here, we performed a large-scale coordinated meta-analysis by pooling structural brain measures from 1,085 subjects with and without insomnia symptoms across three international ENIGMA-Sleep cohorts. The influence of insomnia on MRI-based brain morphometry using an insomnia brain score was assessed. We collected case-control data from two sites, as well as population-based data from another site. Within each cohort, we used an ordinary least-squares linear regression to investigate the link between the individual regional cortical thickness and subcortical volumes and the presence of insomnia symptoms. Then, we performed a fixed-effects meta-analysis across cohorts based on the first-level results. For the insomnia brain score, weighted logistic ridge regression was performed on one sample, which separated patients with insomnia disorder from controls to train a model based on the segmentation measurements. Afterward, the insomnia brain scores were validated using the other two samples. The model was used to predict the log-odds of the subjects with insomnia given individual insomnia-related brain atrophy. After adjusting for multiple comparisons, we did not detect any significant associations between insomnia symptoms and cortical or subcortical volumes, nor could we identify a global insomnia-related brain atrophy pattern. The current study found inconsistent brain morphology differences between individuals with and without insomnia across three independent cohorts. Further large-scale cross-sectional and longitudinal studies using both structural and functional neuroimaging data are warranted to decipher the pathophysiology of insomnia at the brain level.