IRCCS San Raffaele Scientific Institute Showcase

Several factors may affect response to treatment in Major Depressive Disorder (MDD) including immune/inflammatory alterations and regional brain volumes, particularly in hippocampal regions which have shown to be influenced by inflammatory status. Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker found to be elevated in depressed women in large population studies. Here we investigate the effect of NLR on treatment response in MDD patients, and the role of sex and hippocampal volume on influencing this relationship. A sample of 124 MDD depressed inpatients (F = 80) underwent MRI acquisition, admission NLR was calculated by dividing absolute neutrophil by absolute lymphocyte counts and depression severity was assessed at admission and discharge via the Hamilton Depression Rating Scale (HDRS). As a measure of treatment response, delta HDRS was calculated. We found a significant moderation effect of sex on the relationship between NLR and Delta HDRS: a negative relation was found in females and a positive one in males. NLR was found to negatively affect hippocampal volumes in females. Both left and right hippocampal volume positively associated with Delta HDRS. Finally, left hippocampal volume mediated the effect of NLR on Delta HDRS in females. Sex moderated the relation between inflammation and treatment response in line with previous reports linking inflammation to hampered antidepressant effect in females. Further, this effect is partially mediated by hippocampal volume, suggesting that antidepressant response may be hampered by the detrimental effect of inflammation on the brain.

Bipolar disorder (BD) and major depressive disorder (MDD) are severe psychiatric illnesses that share among their environmental risk factors the exposure to adverse childhood experiences (ACE). Exposure to ACE has been associated with long-term changes in brain structure and the immune response. In the lasts decades, brain abnormalities including alterations of white matter (WM) microstructure and higher levels of peripheral immune/inflammatory markers have been reported in BD and MDD and an association between inflammation and WM microstructure has been shown. However, differences in these measures have been reported by comparing the two diagnostic groups. The aim of the present study was to investigate the interplay between ACE, inflammation, and WM in BD and MDD. We hypothesize that inflammation will mediate the association between ACE and WM and that this will be different in the two groups. A sample of 200 patients (100 BD, 100 MDD) underwent 3T MRI scan and ACE assessment through Childhood Trauma Questionnaire. A subgroup of 130 patients (75 MDD and 55 BD) underwent blood sampling for the assessment of immune/inflammatory markers. We observed that ACE associated with higher peripheral levels of IL-2, IL-17, bFGF, IFN-γ, TNF-α, CCL3, CCL4, CCL5, and PDGFBB only in the BD group. Further, higher levels of CCL3 and IL-2 associated with lower FA in BD. ACE were found to differently affect WM microstructure in the two diagnostic groups and to be negatively associated with FA and AD in BD patients. Mediation analyses showed a significant indirect effect of ACE on WM microstructure mediated by IL-2. Our findings suggest that inflammation may mediating the detrimental effect of early experiences on brain structure and different mechanism underlying brain alterations in BD and MDD.

Despite the increasing availability of antidepressant drugs, a high rate of patients with major depression (MDD) does not respond to pharmacological treatments. Brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling is thought to influence antidepressant efficacy and hippocampal volumes, robust predictors of treatment resistance. We therefore hypothesized the possible role of BDNF and neurotrophic receptor tyrosine kinase 2 (NTRK2)-related polymorphisms in affecting both hippocampal volumes and treatment resistance in MDD. A total of 121 MDD inpatients underwent 3T structural MRI scanning and blood sampling to obtain genotype information. General linear models and binary logistic regressions were employed to test the effect of genetic variations related to BDNF and NTRK2 on bilateral hippocampal volumes and treatment resistance, respectively. Finally, the possible mediating role of hippocampal volumes on the relationship between genetic markers and treatment response was investigated. A significant association between one NTRK2 polymorphism with hippocampal volumes and antidepressant response was found, with significant indirect effects. Our results highlight a possible mechanistic explanation of antidepressant action, possibly contributing to the understanding of MDD pathophysiology.

Due to the overlapping depressive symptomatology with major depressive disorder (MDD), 60% of patients with bipolar disorder (BD) are initially misdiagnosed, calling for the definition of reliable biomarkers that can support the diagnostic process. Here, we optimized a machine learning pipeline for the differentiation between depressed BD and MDD patients based on multimodal structural neuroimaging features. Diffusion tensor imaging (DTI) and T1-weighted magnetic resonance imaging (MRI) data were acquired for 282 depressed BD (n = 180) and MDD (n = 102) patients. Images were preprocessed to obtain axial (AD), radial (RD), mean (MD) diffusivity, fractional anisotropy (FA), and voxel-based morphometry (VBM) maps. Each feature was entered separately into a 5-fold nested cross-validated predictive pipeline differentiating between BD and MDD patients, comprising: confound regression for nuisance variables removal, feature standardization, principal component analysis for feature reduction, and an elastic-net penalized regression. The DTI-based models reached accuracies ranging from 75% to 78%, whereas the VBM model reached 61% of accuracy. All the models were significantly different from a null model distribution at a 5000-permutation test. A 5000 bootstrap procedure revealed that widespread differences drove the classification, with BD patients associated to overall higher values of AD and FA, and grey matter volumes. Our results suggest that structural neuroimaging, in particular white matter microstructure and grey matter volumes, may be able to differentiate between MDD and BD patients with good predictive accuracy, being significantly higher than chance-level.

These files contain the raw images and dataset used to generate Figures 1A, 5 (panels B, C, and G), 6 (panels A, D, E and F), and S3A of the article titled “Blockade of αvβ6 and αvβ8 integrins with a chromogranin A-derived peptide inhibits TGFβ activation in tumors and suppresses tumor growth” by A.M. Gasparri, A. Pocaterra, B. Colombo, G. Taiè, C. Gnasso, A. Gori, F. Pozzi, A. Smith, F. Magni, A. Ugolini, M. Doglio, M.C. Bonini, A. Mondino, A. Corti, and C. Curnis, published in J Exp Clin Cancer Res 44, 88 (2025). https://doi.org/10.1186/s13046-025-03352-4 The research leading to these findings was funded by Associazione Italiana per la Ricerca sul Cancro (AIRC) under IG 2019 – ID. 23470 project – P.I. Angelo Corti; Fondazione AIRC 5 per Mille 2019 program (ID. 22737), P.I. MC Bonini, Group Leader A. Corti and A. Mondino; collectively supported by the national funding organizations under the framework of the ERA-NET TRANSCAN-3 initiative (ReachGlio project, ID: TRANSCAN2022-784-017 – Italian Ministry of Health ID: ERP-2022-23683648 to F. Curnis); and National Recovery and Resilience Plan (NRRP), M6/C2_CALL 2023 (project: POC-2023-12377318 to F. Curnis) funded by the European Union – NextGenerationEU.

raw data and images for the genertion of the figures in the manuscript "Ceruloplasmin administration in the preclinical mouse model of aceruloplasminemia reveals a sex-related variation in biodistribution" by Belloli S, Monterisi C, Rainone P, Coliva A, Zanardi A, Conti A, Caricasole A, Moresco RM, Alessio M. (Published in Communications Biology, 2025)

These datasets include levels of whole blood RNA features selected by machine learning algorithms and applied to distinct train and test cohorts of patients with clinically isolated syndromes, multiple sclerosis and healthy controls recruited and analyzed for the project Grant RF-2018- 12367731 that was funded by the Italian Ministry of Health.

Data referred to the study financed by the Ministry of Health (RF-2018-12367731) and published in the article https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1436717/full

Data related to manuscript "HNF4α, SP1 and c-myc are master regulators of CNS autoimmunity" by Colombo et al, J Autoimmun. 2023 Jul;138:103053. doi: 10.1016/j.jaut.2023.103053.

Infertility affects almost 15–20% of couples of reproductive age in Western countries, and a pure male factor is responsible for about half of these cases. Despite infertile men show a poorer general health status compared to age-matched fertile men, a comprehensive understanding of the association between infertility and the overall impoverishment of men's health was still lacking. In the manuscript “Specific types of male infertility are correlated with T cell exhaustion or senescence signatures" (doi.org/10.1038/s41467-025-56193-2), we investigated the immune system of primary infertile men. We showed that both the semen and blood of these subjects exhibit a pro-inflammatory status resembling the one found in elderly men, suggesting that infertility could be linked to early aging of the immune system. The datasets loaded contain all the clinical and immunological data supporting our conclusions and that have been used to build the main and supplementary figures/tables of the manuscript. An additional file (raw_data_description) contains the main guidelines to correctly associate the raw data with the corresponding figure/table in the manuscript.