Plasminogen Activator Inhibitor-1 in the Pathophysiology of Late Life Depression

IF 3.6 3区医学 Q2 GERIATRICS & GERONTOLOGY

International Journal of Geriatric Psychiatry Pub Date : 2024-11-22 DOI:10.1002/gps.70015

L. Métivier, D. Vivien, R. Goy, V. Agin, E. Bui, S. Benbrika

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引用次数: 0

Abstract

Introduction

Late life depression (LLD) is characterized by specific clinical features including a high frequency of vascular form and frequent antidepressant treatment resistance. The expression and functions of the serine protease inhibitor, Plasminogen Activator Inhibitor-1 (PAI-1) is known to be altered by aging, vascular damage, insulin levels associated with a sedentary lifestyle, chronic stress leading to hypercortisolemia, and inflammatory changes linked to stress responses. These phenomena would be implicated in LLD like vascular depression. This article thus aims to review the existing literature regarding the association between LLD and plasmatic levels of PAI-1, a marker of hypofibrinolysis. We hypothesize that increased age would be associated with changes in PAI-1 plasma level and function which influence LLD pathogenesis and its treatment.

Results

Although a large number of studies on PAI-1 changes in the elderly exist, studies about its implications in LLD are sparse. Despite heterogeneous findings regarding the direction of variation in plasmatic PAI-1 levels among elderly participants with LLD, all studies demonstrated an association between PAI-1 levels and current or remitted depressive symptoms. Moreover, disruptions in the concentrations of other biological markers influencing PAI-1 expression, such as cytokines or adipokines, were also observed, notably an increase in the levels of interleukins 6 and 8.

Discussion

LLD genesis appears to be influenced by PAI-1 regulatory loops which are implicated in senescence or cell death. The resistance to antidepressant treatment appears to be linked to distinct biological profiles involving inflammatory and fibrinolytic factors. Taken together these data suggest that PAI-1 pathway may be a promising target of treatment development efforts for LLD, and depression in general.

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晚年抑郁症病理生理学中的凝血酶原激活物抑制剂-1

导言晚期抑郁症（LLD）具有特殊的临床特征，包括高频率的血管病变和频繁的抗抑郁治疗抵抗。众所周知，丝氨酸蛋白酶抑制剂--血浆酶原激活物抑制剂-1（PAI-1）的表达和功能会因衰老、血管损伤、与久坐生活方式相关的胰岛素水平、导致高皮质醇血症的慢性压力以及与压力反应相关的炎症变化而发生改变。这些现象都会牵连到类似血管抑郁的 LLD。因此，本文旨在回顾有关低密度脂蛋白血症与纤溶不足标志物 PAI-1 血浆水平之间关系的现有文献。我们假设年龄的增长与 PAI-1 血浆水平和功能的变化有关，而这些变化会影响 LLD 的发病机制和治疗。结果尽管存在大量有关老年人 PAI-1 变化的研究，但有关其对 LLD 影响的研究却很少。尽管关于患有 LLD 的老年人血浆 PAI-1 水平变化方向的研究结果不尽相同，但所有研究都表明 PAI-1 水平与当前或缓解的抑郁症状之间存在关联。此外，还观察到影响 PAI-1 表达的其他生物标记物（如细胞因子或脂肪因子）的浓度发生了变化，尤其是白细胞介素 6 和白细胞介素 8 的浓度增加。讨论 LLD 的形成似乎受到 PAI-1 调节环路的影响，而 PAI-1 与衰老或细胞死亡有关。抗抑郁剂治疗的抗药性似乎与涉及炎症和纤维蛋白溶解因子的不同生物特征有关。综上所述，这些数据表明 PAI-1 通路可能是开发治疗 LLD 和一般抑郁症的一个有希望的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Geriatric Psychiatry 医学-精神病学

CiteScore

6.10

自引率

2.50%

发文量

168

审稿时长

4-8 weeks

期刊介绍： The rapidly increasing world population of aged people has led to a growing need to focus attention on the problems of mental disorder in late life. The aim of the Journal is to communicate the results of original research in the causes, treatment and care of all forms of mental disorder which affect the elderly. The Journal is of interest to psychiatrists, psychologists, social scientists, nurses and others engaged in therapeutic professions, together with general neurobiological researchers. The Journal provides an international perspective on the important issue of geriatric psychiatry, and contributions are published from countries throughout the world. Topics covered include epidemiology of mental disorders in old age, clinical aetiological research, post-mortem pathological and neurochemical studies, treatment trials and evaluation of geriatric psychiatry services.