According to the WHO, Major Depressive Disorder (MDD) is the 4th leading cause of disability worldwide and the second most common disease after cardiovascular events. MDD is a multifactorial disease driven by a combined effect of genetic, epigenetic, psychological, biological, and environmental factors including compositional and functional changes in the gut microbiome. The microbiome exerts its effect on the nervous system, the so-called microbiome-gut-brain (MGB) axis, through the synthesis of metabolites that induce neurotransmitter production and immune system activation. In addition to influencing specific brain functions, there is a growing evidence that the gut microbiome may also affect epigenetic patterns and indirectly influence the efficacy of several drugs, including antidepressants. Both diagnosis and treatment of MDD patients remain challenging due to the lack of early biomarkers and personalized treatment options, especially for pediatric patients.
To address these issues, in this context, the OPADE project aims to identify early biomarkers in MDD to tailor personalized drug treatments. three hundred fifty patients between fourteen and fifty years will be recruited in 6 Countries (Italy, Colombia, Spain, Netherlands, Turkey) for twenty-four months. Real-time electroencephalogram (EEG) and patient cognitive assessment will be correlated with biological samples analysis. A patient empowerment tool (Chatbot) will be deployed to ensure patient commitment and to translate patient stories into data. The study will use a multi-omics approach including: metagenomic sequencing to characterize the microbiome composition; metabolomics to detect circulating metabolites; transcriptomics to quantify microRNAs; epigenomics to assess methylation variability between and within groups and immune assays to analyze the antibody immune response and inflammatory profiles (cytokines, interleukins and growth factors). Cortisol and lipoproteins will also be quantified. Resulting data will be used to train the Artificial Intelligence/Machine Learning (AI/ML) predictive tool. In summary, the OPADE project aims to analyze MDDs at different levels and with different approaches, leading to the constitution of a ML algorithm for improving diagnosis and treatment, preventing relapse by combining genetics, epigenetics, microbiome, immune response data, and the non-molecular biomarkers such as medical history, electroencephalography (EEG), from subjects with MDD.
