Epigenetic regulation is crucial for neuronal functioning and synaptic plasticity and epigenetic mechanisms were consistently reported as highly involved in pathophysiology of psychiatric disorders. Epigenetic dysregulation could account for the high heterogeneity of these disorders, their phenotypic variability within the same subjects and are in line with the hypothesis of shared risk factors, genetic vulnerabilities and biological pathways between the addiction, mood, anxiety and psychotic disorders. In addition, serious psychiatric disorders preferentially affect young individuals, with the first symptoms (or prodromes) occurring between 15 and 25 years old, during the critical period of adolescence when the brain is undergoing major maturational processes and when the individuals are more likely to experience psychotropic substances. Substance use, especially cannabis is a recognized risk factor for schizophrenia raising the question of its role in the emergence of psychotic symptoms and in sustaining depressive and/or anxiety dimensions. The biological substratum of the interplay between substance use/abuse (mostly cannabis) and psychiatric risk lays in epigenetic regulation. This latter involves dynamic processes that have a role in controlling gene expression levels, among which methylation of genes on cytosine–phosphate–guanine (CpG) dinucleotides have been the main focus of research. Regulation by micro-ribonucleic nucleic acids (miRNAs) is another epigenetic process known to be more dynamic than DNA methylation changes. Little is known regarding the specific and dynamic epigenetic changes during conversion to psychosis. We hypothesize that the vulnerability to the emergence of psychosis is associated with changes in miRNAs and that cannabis exposure modifies that same critical pathways. EPI_young aims to go further in understanding the epigenetic changes that determine the emergence of a psychotic disorder and the precise influence of cannabis use/abuse in young people. We intend to use a systematic omics approach in a longitudinal cohort of UHR subjects exhaustively characterized at the phenotypic and molecular level. The specific objectives will be: 1. To determine the dynamic changes in the methylome and mirnome during the conversion to psychosis in young adults with longitudinal follow-up. 2. To determine the methylomic and miRNA signatures of cannabis use in young adults with longitudinal follow-up. 3. To identify the overlap between the previously identified epigenetic signatures of the psychotic transition and the cannabis use. EPI_young has many originality points and will contribute to said state of the art because it represents: a. a highly tailored approach to an evolutive and complex mental health condition : Dynamic processes need dynamic (clinical and molecular) evaluations, strongly supported by a network of clinical research and personalized care: The ICAAR cohort (Influence du Cannabis sur l'émergence de symptomes psychopathologiques des Adolescents et jeunes Adultes présentant un état mental à Risque) is the most clinically and biologically supplied longitudinal cohort of young UHR and non UHR individuals at the international level. b. an innovative approach to integrate longitudinal multi-omic levels: Multi-omic analysis of complex traits will be used to achieve a more through and informative interrogation of genotype-phenotype associations rather than an analysis that uses only a single data type. Combining multiple data types (with a translational approach) compensates for missing or unreliable information from a single level. Multiples sources of evidence pointing to the same pathway are less likely to lead to false positives. c. an unique opportunity to test predictive value of the epigenetic changes during conversion to psychosis and cannabis use/abuse in young adults opening roads for staging biomarkers and prospective research for therapeutic/preventive endpoints.