This observational study aims to identify the underlying neurobiological and environmental mechanisms that influence vulnerability or resilience to mental illness in the context of infection and their contribution to severe infective outcomes in people with pre-existing mental illness. The main questions it aims to answer are:

• How do viral infections influence the development of mental illness?
• What neurobiological and environmental factors contribute to influence the development of mental illness following infection?
• How do these factors relate to the severity of infectious illness in people with pre-existing mental disorders?

Researchers will move from large population databases to well-defined, deeply characterised samples to explore the association between infection and subsequent mental health outcomes, and the biological mechanisms behind these changes.

Participants's data has already been collected.

Inclusion Criteria for the MOOD-MI cohort:

• A depressive episode according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria in the course of MDD or BD with:

  • HDRS score > 17
  • Age 18-65 years;

• Signed informed consent, able to understand, speak and write the national language

Inclusion Criteria for the COVID-MI cohort:

• Having a positive nasopharyngeal swab for COVID-19 in the last 36 months;
• Age between 18-25 years;
• Signed informed consent, able to understand, speak and write the national language

Exclusion Criteria for the MOOD-MI cohort:

• History of schizophrenia, schizoaffective disorder, psychosis not otherwise specified; anorexia or bulimia nervosa;
• Taking following medications: antipsychotics, anticonvulsants, mood stabilizers; stimulants
• Active infection requiring antibiotics therapy;
• Immunosuppressed patient or other chronic diseases
• Signs of active infection requiring treatment
• Use of anti-inflammatory medication on a regular basis for a chronic inflammatory/autoimmune Disorder. Forbidden treatment: corticosteroids, Non Steroidal Anti-inflammatory Drugs, immunosuppressant IV-Ig based treatment
• Ongoing fever, infection treated by antibiotics or uncontrolled diabetes type I or II;
• Existing cancer or history of cancer in the last 5 years (except skin epidermoid cancer or in-situ cervix cancer);
• Known HIV infection or clinically manifest Acquired Immune Deficiency Syndrome (AIDS), Parkinson's or Alzheimer's disease, or any other serious condition likely to interfere e with the conduct of the trial;
• Abuse of drugs or alcohol in the past 6 months

Exclusion Criteria for the COVID-MI cohort:

• Comorbidity for psychotic disorders, verified by SCID-CV;
• Current and clinically significant substance use disorder;
• Current comorbidity with neurological conditions or severe head trauma, general brain disorder preceding the emergence of PASC, including microhaemorrhages and/or ischaemia occurring during the acute phase of COVID;
• Neuropsychological diagnosis of intellectual disability;
• Presence of contraindications to blood sampling and/or MRI;
• Pregnancy status at the time of recruitment.

Other exclusion criteria related to the MRI procedure include:

• Aneurysm clip
• Implanted neural stimulator
• Implanted cardiac pacemaker or auto-defibrillator
• Cochlear implant
• Ocular foreign body (e.g., metal shavings)
• Any implanted device (pumps, infusion devices, etc)
• Shrapnel injuries.

For epidemiological cohorts (MoBa, TOP, CHS) age between 18 and 65 ya, diagnosis of a severe mental illness (Schizophrenia, Major Depression, Bipolar disorder, anxiety disorders),

Patients diagnosed with major depressive disorder or bipolar disorder (MOOD-MI cohort) and patients with COVID-19 (COVID-MI cohort). For epidemiological cohorts (MoBa, TOP, CHS) any patients with severe mental illnesses