protocolSection identificationModule nctId: NCT06306209, orgStudyIdInfo id: DeFLAME, briefTitle: Inflammatory Control of Antidepressant Efficacy: a Pharmaco-epigenetic Approach, statusModule overallStatus: RECRUITING, startDateStruct date: 2021-05-18, primaryCompletionDateStruct date: 2024-11-30, completionDateStruct date: 2025-01-14, studyFirstPostDateStruct date: 2024-03-12, lastUpdatePostDateStruct date: 2024-03-12, sponsorCollaboratorsModule leadSponsor name: IRCCS San Raffaele, class: OTHER, descriptionModule briefSummary: Major depressive disorder (MDD) is a chronic, recurring and potentially life-threatening illness that affects up to 10% of the population across the globe.It posits that the increase in serotonin levels induced by Selective Serotonin Reuptake Inhibitors (SSRIs) does not affect mood per se, but enhances brain plasticity and thus amplifies the influence of the environment on the individual. Thus, SSRI treatment has not a univocal effect but, in a favorable environment, it would lead to a reduction of symptoms while in a stressful environment might lead to a worse prognosis.Such innovative view opens new perspectives on how to improve SSRI efficacy by controlling the environment. However, often it is not possible to act on the quality of the living environment because of constraints due to patient's personal history and unchangeable life circumstances. In these cases, the pharmacological modulation of the factors underlying the link between living environment and SSRI efficacy represents a novel and desirable strategy to improve treatment outcome even in patients living in adverse conditions, which are very common in depressed patients. Inflammatory levels are markedly affected by the socioeconomic status and thus by the quality of the living environment. The hypothesis of the present project is that inflammation mediates the influence of the environment on SSRI outcome.Therefore, the control of inflammatory levels is a promising strategy to improve treatment efficacy and overcome the limited SSRI efficacy, especially when administered in patients living in adverse conditions. A further hypothesis is that the influence of the environment on inflammation, in turn affecting SSRI efficacy, occurs through epigenetic modifications. Therefore, the project aims at developing a pharmaco-epigenetic approach as effective treatment for MDD. In addition, through neuroimaging investigations, it will provide important information about functional and structural brain modifications associated to SSRI efficacy in patients.Both males and females will be considered because MDD is twice as common in women than men, suggesting that different mechanisms may underlie the psychopathology in the two sexes., conditionsModule conditions: Mood Disorders, conditions: Major Depressive Disorder, designModule studyType: OBSERVATIONAL, designInfo observationalModel: COHORT, timePerspective: PROSPECTIVE, enrollmentInfo count: 80, type: ESTIMATED, armsInterventionsModule interventions name: Treatment as usual (TAU), i.e., pharmacotherapy plus clinical management, outcomesModule primaryOutcomes measure: The potential role of inflammation as the causal link between the quality of the environment and SSRI efficacy, primaryOutcomes measure: interaction between early stress and recent stress on the response to treatment and the role of inflammation, primaryOutcomes measure: identification of neurobiological predictors of response to treatment, primaryOutcomes measure: identification of neurobiological predictors of response to treatment, primaryOutcomes measure: identification of neurobiological predictors of response to treatment, secondaryOutcomes measure: epigenetic changes in cytokine regulating genes which could mediate the effect of stress on response to treatment., eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 65 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: IRCCS Ospedale San Raffaele, status: RECRUITING, city: Milan, state: Mi, zip: 20132, country: Italy, contacts name: Sara sp Poletti, phd, role: CONTACT, phone: +390226433156, email: poletti.sara@hsr.it, geoPoint lat: 45.46427, lon: 9.18951, hasResults: False