Brain, behavior, and immunity · 2025
Inflammation and psychomotor retardation in depression: The moderating role of glymphatic system.
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Liang Qunjun, Peng Bo, Chen Shengli, Wei Hongyue, Lin Shiwei, Lin Xiaoshan, Li Ying, Zhang Yingli, Zhou Zhifeng, Xu Ziyun, Hou Gangqiang, Qiu Yingwei
Аннотация
BACKGROUND: Psychomotor retardation (PMR) is a predominant symptom in patients with major depressive disorder (MDD). The relationship between inflammation and PMR is the subject of ongoing debate. The glymphatic system (GS) is a waste clearance system in the brain that interacts with the immune system. Herein, we hypothesized that GS function moderates the association between inflammation and PMR.
METHODS: A total of 67 patients with MDD and 67 healthy controls (HCs) were recruited and underwent MRI scanning. PMR and inflammation, which were evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in peripheral blood, were assessed in all patients. Diffusion tensor imaging analysis along the perivascular space was used to assess GS function. Functional connectivity (FC) and morphology within the motor circuit were also assessed. Moderation models were constructed to estimate the effect of GS function as a moderator of the relationships between hsCRP level and PMR and between hsCRP level and motor cortex FC and morphology.
RESULTS: GS function in patients was impaired compared with that in HCs (t = -2.635, p = 0.009). Moderation models showed that hsCRP level significantly aggravated PMR severity at low levels of GS function, whereas this effect was negligible in patients with optimal GS function (F = 6.725, p = 0.021). GS function also exhibited a moderation effect on inflammation-related alterations in morphology (F = 13.86, p = 0.047) and FC (F = 13.765, p < 0.001) in the motor circuit.
CONCLUSION: A well-functioning GS mitigates inflammation-induced PMR and protects neurons from inflammatory damage. Given its moderating effect, GS function may play a crucial role in MDD psychopathology, and targeting GS function may have therapeutic value as an MDD treatment strategy.
METHODS: A total of 67 patients with MDD and 67 healthy controls (HCs) were recruited and underwent MRI scanning. PMR and inflammation, which were evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in peripheral blood, were assessed in all patients. Diffusion tensor imaging analysis along the perivascular space was used to assess GS function. Functional connectivity (FC) and morphology within the motor circuit were also assessed. Moderation models were constructed to estimate the effect of GS function as a moderator of the relationships between hsCRP level and PMR and between hsCRP level and motor cortex FC and morphology.
RESULTS: GS function in patients was impaired compared with that in HCs (t = -2.635, p = 0.009). Moderation models showed that hsCRP level significantly aggravated PMR severity at low levels of GS function, whereas this effect was negligible in patients with optimal GS function (F = 6.725, p = 0.021). GS function also exhibited a moderation effect on inflammation-related alterations in morphology (F = 13.86, p = 0.047) and FC (F = 13.765, p < 0.001) in the motor circuit.
CONCLUSION: A well-functioning GS mitigates inflammation-induced PMR and protects neurons from inflammatory damage. Given its moderating effect, GS function may play a crucial role in MDD psychopathology, and targeting GS function may have therapeutic value as an MDD treatment strategy.