Depression is still a frequent and debilitating disease that needs more effective therapeutic strategies. The World Health Organization has classified it among the international health emergencies.
A study coordinated by Sapienza and Istituto Superiore di Sanità has discovered the fundamental role of the environment in the pharmacological treatment of the disease, demonstrating on the murine model that the effect of therapy may vary depending on the environmental context in which it is administered.

The research, published in the journal Molecular Pshychiatry, is coordinated by Laura Maggi and Cristina Limatola of the Physiology and Pharmacology Department, Sapienza and Igor Branchi of the Istituto Superiore di Sanità, in collaboration with Silvia Alboni of the University of Modena and Reggio Emilia (Unimore) and the University of Zurich.

Researchers have shown that when the drug is administered in a stimulating environment, there is a cerebral elevation of neurotrophic support in the hippocampus  and a normalization of the hypothalamic-pituitary-adrenal axis function. Conversely, when the drug is administered in a stressful environment, a worsening of the behavioral phenotype, an increase in brain plasticity, and a reduction in neurogenesis are observed.
"The ability to identify the quality of the environment as an important factor in directing the effect of antidepressant treatment - says Laura Maggi - could be a major breakthrough in improving depression therapy".

The work focused on selective serotonin reuptake inhibitors (SSRIs), a category of drugs used in the treatment of major depression whose efficacy is highly uncertain and variable.
In particular, the researchers examined fluoxetine, a drug belonging to this class. From the results of the research it seems that fluoxetine does not directly modify the mood but, through an increase in brain plasticity, makes the individual more susceptible to the effects of the environment.

Experiments were conducted on mice exposed to chronic stress. Fluoxetine, by acting on the plasticity of the brain, creates a sort of window of opportunity for change, whose direction, or the course of the pathology toward improving or worsening the subject, is established by the environment.

Thus, the results show that the direction of behavioral, structural and molecular effects depends on the quality of the environment in which the drug is administered.
The observations proposed by the researchers may provide a justification for the known variable effects of SSRIs found in clinical practice and to target strategies to improve their effectiveness by monitoring and improving the environmental conditions in which these drugs are administered.