protocolSection identificationModule nctId: NCT06306248, orgStudyIdInfo id: PNRR-MAD-2022-12375716, briefTitle: Immune Activation, Neural Plasticity and Depression, statusModule overallStatus: RECRUITING, startDateStruct date: 2023-03-03, primaryCompletionDateStruct date: 2025-03-03, completionDateStruct date: 2025-05-09, 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.Increasing evidence indicates a clear link between immune dysfunction and MDD.Moreover, an activation of inflammatory pathways is associated to a lack of clinical response to antidepressants. Thus, the regulation of inflammation represents a potential approach to modulate the link between the living environment and antidepressant outcome. Light therapy combined with sleep deprivation hastens recovery, with benefits that can be perceived by patients during the first week of treatment. Alteration of the sleep-wake cycle and of sleep structure are core symptoms of MDD.The aims of the present project are (i) to show that neural plasticity and the environmental context are moderating factors of the therapeutic outcome of immune modulation and (ii) to exploit their interplay to set up novel and effective therapeutic strategies for MDD.This is a observational prospective study with non-invasive add-on procedures (Magnetic Resonance without contrast). In this study, 60 patients with a depressive episode in course of MDD and treated with a chronobiological intervention including total sleep deprivation (TSD) + light therapy (LT), as performed in clinical practice, will be studied. All participants enrolled in the study will receive Treatment As Usual (TAU), i.e., pharmacotherapy, chronobiological intervention plus clinical management. Drug prescription will be performed during the clinical management sessions.The study will have a total duration of 24 months. Each subject will participate in the study for 6 months, will undergo Magnetic Resonance Imaging (MRI) and clinical evaluation at baseline, after one week of chronobiological treatment and at 6 months follow-up., conditionsModule conditions: Mood Disorders, conditions: Major Depressive Disorder, conditions: Sleep Deprivation, designModule studyType: OBSERVATIONAL, designInfo observationalModel: COHORT, timePerspective: PROSPECTIVE, enrollmentInfo count: 60, type: ESTIMATED, armsInterventionsModule interventions name: Total sleep deprivation, outcomesModule primaryOutcomes measure: BENEFICIAL EFFECT OF total sleep deprivation in inflamed vs non inflamed patients., secondaryOutcomes measure: Neurobiological markers of prediction and progression of antidepressant 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