Stress-related disorders, including anxiety and depression, affect approximately 8% of the global population, yet around a third of patients do not respond to antidepressant treatment despite a marked increase in their use over the past two decades. The limited success of current therapies highlights major gaps in our understanding of the biological mechanisms underlying stress-related psychopathology.

While research has traditionally focused on neurons, astrocytes are now recognised as key regulators of brain metabolism and emotional behaviour. Chronic stress alters brain metabolism in regions involved in emotional regulation, including the hippocampus and amygdala. Although selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine increase extracellular serotonin levels, their therapeutic effects cannot be explained solely by serotonergic changes, suggesting the involvement of additional signalling pathways. Notably, fluoxetine also enhances the release of astrocytic lactate, a metabolite and signalling molecule essential for emotional regulation; however, the mechanisms driving these metabolic changes remain poorly understood.

In this talk, I will present our ongoing work examining metabolic and morphological adaptations in astrocytes following acute and chronic stress, and show how antidepressants modulate astrocyte function, with particular emphasis on astrocytic metabolism and the release of psychoactive molecules induced by monoaminergic antidepressants, including SSRIs, and rapid-acting antidepressants such as ketamine, and psychedelics.