This project aims to improve the health care provided to people with major depressive disorder (MDD), a disease which is a top cause of disability worldwide. One of the main obstacles to a more effective health care in these patients is represented by clinical heterogeneity, which has not completely elucidated biological correlates. Using a large sample of people with MDD already recruited (n=29,400), the investigators develop a clustering algorithm based on genetic-environmental and brain imaging predictors aimed at identifying homogeneous MDD subgroups. The researchers will then link these subgroups with relevant health outcomes, such as disease recurrency and severity, well-being and functioning, risk of psychiatric and medical comorbidities (e.g. cardiovascular disorders). Replication in independent samples already recruited(n=1380) will prove the validity of the subgroups and expand their clinical characterization. The investigators will develop a classification tool to link the individual's characteristics to the relevant health outcomes and provide corresponding clinical recommendations. The prognostic support tool will be applied to newly recruited samples, feasibility and usefulness according to clinicians's opinion will be assessed (n=120, ongoing recruitment).

Inclusion Criteria:

• diagnosis of depressive episode in Major Depressive Disorder (DSM-5);
• at least one depressive episode preceding the current one;
• aged between 18 and 65;
• score of at least 8 on the Hamilton Depression Rating Scale (HDRS);
• signature of the information form and declaration of informed consent;
• elementary school certificate (as a minimum requirement for understanding the questions presented in the tests);
• native Italian speaker (or bilingualism).

Exclusion Criteria:

• diagnosis of bipolar disorder, cyclothymic disorder, schizophrenia and other psychotic spectrum disorders, neurodevelopmental disorders;
• diagnosis of intellectual disability, epilepsy, neurodegenerative disorders;
• disorders related to the use of drugs or alcohol in the last 6 months (except nicotine and caffeine);
• pregnant or breastfeeding.

Inpatients and outpatients with an ongoing depressive episodes diagnosed accordingly to DSM 5.