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Insomnia and depression are highly comorbid symptoms in both primary insomnia (PI) and major depressive disorder (MDD). In the current study, we aimed at exploring both the homogeneous and heterogeneous brain structure alteration in PI and MDD patients. Sixty-five MDD patients and 67 matched PI patients were recruited and underwent a structural MRI scan. The subjects were sub-divided into four groups, namely MDD patients with higher or lower insomnia, and PI patients with higher or lower severe depression. A general linear model was employed to explore the changes in cortical thickness and volume as a result of depression or insomnia, and their interaction. In addition, partial correlation analysis was conducted to detect the clinical significance of the altered brain structural regions. A main effect of depression on cortical thickness was seen in the superior parietal lobe, middle cingulate cortex, and parahippocampal gyrus, while a main effect of insomnia on cortical thickness was found in the posterior cingulate cortex. Importantly, the interaction between depression and insomnia was associated with decreased gray matter volume in the right orbitofrontal cortex, i.e., patients with co-occurring depression and insomnia showed smaller brain volume in the right orbitofrontal cortex when compared to patients with lower insomnia/depression. These findings highlighted the role of the orbitofrontal cortex in the neuropathology of the comorbidity of insomnia and depression. Our findings provide new insights into the understanding of the brain mechanism underlying comorbidity of insomnia and depression.

The Orbitofrontal Cortex Gray Matter Is Associated With the Interaction Between Insomnia and Depression