The impact of the environmental context on depression care

The role of the environment in the treatment of depression is the main focus of the study “Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment” performed by, among the others, researchers of Unimore and recently published on Molecular Psychiatry. For the first time the authors, including Dr. Silvia Alboni and Prof. Nicoletta Brunello from the Department of Life Sciences, have been able to demonstrate that the response to antidepressant drugs such as SSRI (selective serotonin reuptake inhibitors) depends strictly on the type of environment in which they are administered.

Antidepressant treatment response is likewise the outcome of gene-environment interactions.

This is the main finding of the paper "Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment" recently published on the highly prestigious journal Molecular Psychiatry by Dr. Silvia Alboni and Prof. Nicoletta Brunello, working at the University of Modena and Reggio Emilia in the Department of Life Sciences, who have performed the study in collaboration with an international team including Dr. Laura Maggi from the University of Rome “La Sapienza” and Dr. Igor Branchi from Istituto Superiore di Sanità in Rome and ETH in Zurich (Switzerland).

The work is mainly focused on the effects of selective serotonin reuptake inhibitors (SSRI), the most prescribed drugs used in the treatment of depressive disorders. Despite its wide usage, the efficacy of these antidepressant drugs is notoriously and largely variable and unclear. The study was aimed at unravelling the reason of this variability has evaluated the hypothesis that these inhibitors do not impact on the pathology itself, but rather that the effect may change depending on the type of environment in which they are administered.

Mice placed in a enriched and supportive environment and treated with fluoxetine, a drug belonging to the class of SSRI, have shown a marked improvement from depressive behavior, whereas mice treated with fluoxetine as well, but placed in a poor an less favourable environment have shown a clear worsening of depressive symptoms. According to the researchers, the drug acting on brain plasticity induces a wider opportunity to change toward improvement or worsening according to the quality of the environment.

It has been observed – as stated by Dr. Silvia Alboni and Prof. Nicoletta Brunello – that fluoxetine induces important effects on brain plasticity, independently from its antidepressant effect. In order to demonstrate that fluoxetine treatment does not modify mood directly, but, through an increase of brain plasticity, by making the subject more susceptible to the effect of the environment, we have treated with fluoxetine mice model of depression exposed either to unavoidable and unpredictable stress or to an environment enriched with cognitive and motor stimuli. Our results show that the direction of the behavioral, structural and molecular effects of the drug depends on the quality of the environment in which animals are housed. In particular when the drug is administered in an enriched condition, we were able to observe not only an improvement of the behavioral phenotype, but also an increase of the neurotrophic support in the hippocampus as well as a normalization of the hypothalamus-pituitary-adrenal axis. On the contrary when the drug is given to animals maintained in stressful conditions, we observe a further worsening of the behavioral phenotype and a reduction of neurogenesis in the hippocampus. In conclusion, the identification of the living environment as a moderator of treatment response might represent a critical step in optimizing the therapy of depression, still a highly debilitating and frequent disease that needs, as recently indicated by the WHO, a more effective therapeutic approach.

The publication of this study occurs just when WHO, in occasion of the World health day, has indicated depression as one of the major international emergency in terms of medical, individual, societal and economical impact.

The results obtained by this team provide a possible explanation for the well known variable effects of SSRI in the clinical practice and propose a personalized medicine approach aimed at better matching depressed patients with treatment through selective enhancement of treatment efficacy and avoiding potential harmful consequences.

Original reference:

Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment - Molecular Psychiatry (2017) 22.
S Alboni, R M van Dijk, S Poggini, G Milior, M Perrotta, T Drenth, N Brunello, D P Wolfer, C Limatola, I Amrein, F Cirulli, L Maggi and I Branchi

Open Access

Silvia ALBONI (Modena, March 29th 1975) completed her University studies obtaining the degree in Chemistry and Pharmaceutical Technology summa cum laude in 2000 and the degree in Pharmacy summa cum laude in 2001 at the University of Modena and Reggio Emilia, Italy. She obtained a Specialization in Pharmaceutical Research Methods in 2005 and the PhD in “Drug sciences” (Molecular Pharmacology) in 2004. As doctoral fellow, she spent a period working on molecular mechanisms behind neural transmission at Ecole Normale Supérieure and Institut de Biologie Physico-Chimique in Paris (France), working under the supervision of prof. Stéphane SUPPLISSON. She had a 11-year post-doctoral fellowship at University of Modena and Reggio Emilia under the supervision of prof. Nicoletta BRUNELLO. In 2007 she worked as Associate Researcher at the SCRIPPS Research Institute, MIND Department, a La Jolla (California, USA) in the laboratory directed by prof. Tamas BARTFAI where she started a project on the localization and characterization of the expression of IL-18 and its receptors in the CNS of mice, in collaboration with prof. Bruno CONTI. In 2009, Dr Alboni won the “Young Scientist Award” from the European College of Neuropsychopharmacology that financed the project aimed at evaluating the role of IL-18 in the development of depression following IFN-alpha treatment, carried out in the “Stress, Psychiatry and Immunology” laboratory headed by Dr. Carmine PARIANTE at King’s College of London, UK (from December 2009 to December 2010). In 2011, Dr Alboni won the L'Oréal-UNESCO fellowship "For Women in Science". She is a member of several scientific societies with national and international relevance and she obtained numerous grants for training experiences in foreign countries and to attend international meetings. Dr Alboni is author of numerous scientific publications in peer-reviewed journal (HI 14, 673 citations) and attended to more than 30 national and international congresses in Europe and USA by presenting about 60 abstracts.