Altered default mode network and glymphatic function in insomnia with depression: A multimodal MRI study

Apr 6, 2025Sleep medicine

Changes in the brain's resting activity and waste clearance system in insomnia with depression

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Abstract

Patients with chronic insomnia disorder and comorbid major depression disorder exhibited significantly weakened functional connectivity within the default mode network.

Individuals with chronic insomnia disorder (CID) and major depression disorder (MDD) showed enhanced connectivity in the posterior cingulate cortex with other brain regions.
CID patients with comorbid MDD had a lower glymphatic function, indicated by a reduced ALPS index compared to those with CID alone.
Significant associations were found between depression severity scores and specific imaging metrics, suggesting a link between depressive symptoms and brain connectivity.
A diagnostic model based on imaging features achieved high efficacy for identifying CID with comorbid MDD.

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OBJECTIVES: This study aims to evaluate functional changes in the default mode network (DMN) and glymphatic system in individuals of chronic insomnia disorder (CID) with comorbid major depression disorder (MDD).

METHODS: A total of 112 CID patients and 56 healthy controls with good sleep (GS) were enrolled. CID patients were divided into were further divided into a CID-only group and a group with CID and comorbid MDD. Resting-state functional magnetic resonance imaging (rs-fMRI) assessed DMN dysfunction and its connectivity with external networks. To determine whether comorbid MDD exacerbated the decline in glymphatic function in patients with CID, the diffusion tensor imaging along the perivascular space (DTI-ALPS) index was calculated. Binary logistic regression identified key imaging features for diagnostic modeling.

RESULTS: Patients with CID and comorbid MDD exhibited significantly weakened functional connectivity within the DMN. In contrast, the key node posterior cingulate cortex(PCC) of the default mode network showed enhanced functional connectivity with brain regions outside the DMN, including middle cingulate cortex and supplementary motor area. Regarding the glymphatic system, the lower ALPS index in CID patients with comorbid MDD was lower than in CID patients, indicating reduced glymphatic function compared to those without depression. HAMD scores were significantly associated with bilateral Dyproj values (P < 0.001) and the functional connectivity values of PCC_L-SMA_L and TempP_L-PHC_L (P < 0.01). The diagnostic model developed based on these findings demonstrated high diagnostic efficacy for CID with comorbid MDD.

CONCLUSION: The destabilization of subsystems within the DMN may represent the neurological mechanism through which depression contributes to insomnia. Comorbid depressive disorders may exacerbate glymphatic dysfunction in patients with CID, highlighting the importance of early clinical intervention for depressive symptoms in insomnia disorder.

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Altered default mode network and glymphatic function in insomnia with depression: A multimodal MRI study

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