Altered orientation dispersion index of white matter in individuals with insomnia during the COVID-19 pandemic: A study combining neuroimaging technique and Mendelian randomization

Study objectives: Coronavirus disease 2019 (COVID-19) can lead to insomnia. However, associations between COVID-19-caused insomnia and white matter (WM) changes are unclear. Methods: All subjects had ever been infected with COVID-19. We investigated 89 insomniacs (29 chronic insomniacs, 33 new-onset insomniacs, 27 aggravated insomniacs) and 44 matched non-insomnia participants. Neurite orientation dispersion and density imaging (NODDI) was performed to identify micro-structural alterations of WM, and twelve scales related to sleeping status, memory, attention, learning, emotional status, and executive functions were used. Then, correlations between insomnia/cognitive-behavioral functions and diffusion metrics were tested. To eliminate influence of pre-COVID-19 factors on insomnia, causal relationships between COVID-19 and WM changes were validated by Mendelian randomization (MR) analysis. The significant brain regions of COVID-19-caused insomnia were intersected results of tract-based spatial statistics (TBSS) and MR analyses. Results: Compared to non-insomnia group, insomnia group and its subgroups including post-COVID-19 aggravated or unchanged chronic insomnia group had higher orientation dispersion index (ODI) in extensive brain regions. The left superior longitudinal fasciculus (SLF), left posterior thalamic radiation (PTR), and left cingulate gyrus (CG) were specific brain regions in COVID-19-induced insomnia aggravation. After Bonferroni correction, partial correlation analyses within insomnia group showed that ODI in left SLF was positively correlated with Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), and self-rating anxiety scale (SAS) scores; ODI in the left PTR was positively correlated with PSQI and ISI scores. Conclusions: This study is a continuation of our previous research, which provided potential biomarkers for COVID-19-induced insomnia.