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 disorder (ID). In the present study, we performed a large-scale coordinated meta-analysis by pooling structural brain measures from 1085 subjects (mean [SD] age 50.5 [13.9] years, 50.2% female, 17.4% with insomnia) across three international Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Sleep cohorts. Two sites recruited patients with ID/controls: Freiburg (University of Freiburg Medical Center, Freiburg, Germany) 42/43 and KUMS (Kermanshah University of Medical Sciences, Kermanshah, Iran) 42/49, while the Study of Health in Pomerania (SHIP-Trend, University Medicine Greifswald, Greifswald, Germany) recruited population-based individuals with/without insomnia symptoms 75/662. The influence of insomnia on magnetic resonance imaging-based brain morphometry using an insomnia brain score was then assessed. Within each cohort, we used an ordinary least-squares linear regression to investigate the link between the individual regional cortical 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 (Freiburg), which separated patients with ID 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. Thus, we observed inconsistent brain morphology differences between individuals with and without insomnia across three independent cohorts. Further large-scale cross-sectional/longitudinal studies using both structural and functional neuroimaging are warranted to decipher the neurobiology of insomnia.