Glymphatic Dysfunction: A Bridge Between Sleep Disturbance and Mood Disorders

Tao Yan; Yuefeng Qiu; Xinfeng Yu; Linglin Yang

doi:10.3389/fpsyt.2021.658340

Glymphatic Dysfunction: A Bridge Between Sleep Disturbance and Mood Disorders

Front Psychiatry. 2021 May 7:12:658340. doi: 10.3389/fpsyt.2021.658340. eCollection 2021.

Authors

Tao Yan¹, Yuefeng Qiu², Xinfeng Yu³, Linglin Yang⁴

Affiliations

¹ Department of Psychiatry, Changxing People's Hospital, Huzhou, China.
² Department of Psychiatry, Zhejiang Hospital, Hangzhou, China.
³ Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Psychiatry, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Mounting evidence demonstrates a close relationship between sleep disturbance and mood disorders, including major depression disorder (MDD) and bipolar disorder (BD). According to the classical two-process model of sleep regulation, circadian rhythms driven by the light-dark cycle, and sleep homeostasis modulated by the sleep-wake cycle are disrupted in mood disorders. However, the exact mechanism of interaction between sleep and mood disorders remains unclear. Recent discovery of the glymphatic system and its dynamic fluctuation with sleep provide a plausible explanation. The diurnal variation of the glymphatic circulation is dependent on the astrocytic activity and polarization of water channel protein aquaporin-4 (AQP4). Both animal and human studies have reported suppressed glymphatic transport, abnormal astrocytes, and depolarized AQP4 in mood disorders. In this study, the "glymphatic dysfunction" hypothesis which suggests that the dysfunctional glymphatic pathway serves as a bridge between sleep disturbance and mood disorders is proposed.

Keywords: aquaporin-4; astrocyte; bipolar disorder; depression; glymphatic system; sleep.