The Association Between Antidepressant Effect of SSRIs and Astrocytes: Conceptual Overview and Meta‐analysis of the Literature

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Beina Chen
  • Manman Zhang
  • Ming Ji
  • Wenliang Gong
  • Binjie Chen
  • Robert Zorec
  • Matjaž Stenovec
  • Baoman Li


Major depressive disorders (MDD) a worldwide psychiatric disease, is yet to be adequately controlled by therapies; while the mechanisms of action of antidepressants are yet to be fully characterised. In the last two decades, an increasing number of studies have demonstrated the role of astrocytes in the pathophysiology and therapy of MDD. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants. It is generally acknowledged that SSRIs increase serotonin levels in the central nervous system by inhibiting serotonin transporters, although the SSRIs action is not ideal. The SSRIs antidepressant effect develops with considerable delay; their efficacy is low and frequent relapses are common. Neither cellular nor molecular pharmacological mechanisms of SSRIs are fully characterised; in particular their action on astrocytes remain underappreciated. In this paper we overview potential therapeutic mechanisms of SSRIs associated with astroglia and report the results of meta-analysis of studies dedicated to MDD, SSRIs and astrocytes. In particular, we argue that fluoxetine, the representative SSRI, improves depressive-like behaviours in animals treated with chronic mild stress and reverses depression-associated decrease in astrocytic glial fibrillary acidic protein (GFAP) expression. In addition, fluoxetine upregulates astrocytic mRNA expression of 5-hydroxytriptamin/serotonin2B receptors (5-HT2BR). In summary, we infer that SSRIs exert their anti-depressant effect by regulating several molecular and signalling pathways in astrocytes.

Bibliographical metadata

Original languageEnglish
JournalNeurochemical research
Early online date1 Feb 2021
Publication statusPublished - 1 Feb 2021