Profiling Vulnerability and Resilience for Mental Illness Following Viral Infections

NCT06945627 | Active Not Recruiting

• 1 other identifier: ERP-2023-23684210
• Study Type: observational
• Target: 408,551
• Locations: 4 countries
• Sites: 4

Brief Summary

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.

Conditions

Severe Mental Illness; Inflammation; Viral Infections; Mood Disorders; Schizophrenia

Outcome Measures

Primary Outcomes (2)

• number of hospital admission for mental illness after infection diagnosis

  number of onset or relapse of mental illness following infection

  3 years

• number of infections (Pathogen Burden Summary - PBS) in patients with mental illness

  number of samples positive for antibodies for viruses associated with Mental illness in the literature (IgG, expressed as AU/mL)

  3 years

Secondary Outcomes (4)

• Environmental risk and resilience factors for mental illness and severe outcomes

  3 years

• Neurobiological risk and resilience factors for mental illnesses and severe outcomes

  3 years

• Predictive risk models based on an individual biological and environmental signatures

  3 years

• genes or proteins that might be modified using drugs

  3 years

Study Arms (8)

Trans-D

Other: This research doesn't involve any kind of intervention on the study participants

Cov-N-Psy

Other: This research doesn't involve any kind of intervention on the study participants

CHS1

Other: This research doesn't involve any kind of intervention on the study participants

CHS2

Other: This research doesn't involve any kind of intervention on the study participants

MOOD-MI

Other: This research doesn't involve any kind of intervention on the study participants

COVID-MI

Other: This research doesn't involve any kind of intervention on the study participants

MoBa

Other: This research doesn't involve any kind of intervention on the study participants

TOP

Other: This research doesn't involve any kind of intervention on the study participants

Interventions

This research doesn't involve any kind of intervention on the study participants OTHER

This research doesn't involve any kind of intervention on the study participants

CHS1; CHS2; COVID-MI; Cov-N-Psy; MOOD-MI; MoBa; TOP; Trans-D

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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;

Sponsors & Collaborators

• Sara Poletti: lead

Study Sites (4)

University of Antwerp

Antwerp, Belgium, 2570, Belgium

Location

University of Haifa

Haifa, Israel, 3498838, Israel

Location

IRCCS Ospedale San Raffaele

Milan, Italy, 20132, Italy

Location

University of Oslo

Oslo, Norway, 0424, Norway

Location

Related Publications (22)

• Lalousis PA, Schmaal L, Wood SJ, Reniers RLEP, Barnes NM, Chisholm K, Griffiths SL, Stainton A, Wen J, Hwang G, Davatzikos C, Wenzel J, Kambeitz-Ilankovic L, Andreou C, Bonivento C, Dannlowski U, Ferro A, Lichtenstein T, Riecher-Rossler A, Romer G, Rosen M, Bertolino A, Borgwardt S, Brambilla P, Kambeitz J, Lencer R, Pantelis C, Ruhrmann S, Salokangas RKR, Schultze-Lutter F, Schmidt A, Meisenzahl E, Koutsouleris N, Dwyer D, Upthegrove R; PRONIA Consortium. Neurobiologically Based Stratification of Recent-Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes. Biol Psychiatry. 2022 Oct 1;92(7):552-562. doi: 10.1016/j.biopsych.2022.03.021. Epub 2022 Apr 12.

  PMID: 35717212 BACKGROUND

• Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016 Dec;21(12):1696-1709. doi: 10.1038/mp.2016.3. Epub 2016 Feb 23.

  PMID: 26903267 BACKGROUND

• Zhang Y, Wang J, Ye Y, Zou Y, Chen W, Wang Z, Zou Z. Peripheral cytokine levels across psychiatric disorders: A systematic review and network meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jul 13;125:110740. doi: 10.1016/j.pnpbp.2023.110740. Epub 2023 Mar 8.

  PMID: 36893912 BACKGROUND

• Tylee DS, Sun J, Hess JL, Tahir MA, Sharma E, Malik R, Worrall BB, Levine AJ, Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, Crawford A, Grant SFA, Polychronakos C, Bradfield JP, Sleiman PMA, Hakonarson H, Ellinghaus E, Elder JT, Tsoi LC, Trembath RC, Barker JN, Franke A, Dehghan A; 23 and Me Research Team; Inflammation Working Group of the CHARGE Consortium; METASTROKE Consortium of the International Stroke Genetics Consortium; Netherlands Twin Registry; neuroCHARGE Working Group; Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium; Faraone SV, Glatt SJ. Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data. Am J Med Genet B Neuropsychiatr Genet. 2018 Oct;177(7):641-657. doi: 10.1002/ajmg.b.32652. Epub 2018 Oct 16.

  PMID: 30325587 BACKGROUND

• Shorter JR, Meijsen J, Nudel R, Krebs M, Gadin J, Mikkelsen DH, Nogueira Avelar E Silva R, Benros ME, Thompson WK, Ingason A, Werge T. Infection Polygenic Factors Account for a Small Proportion of the Relationship Between Infections and Mental Disorders. Biol Psychiatry. 2022 Aug 15;92(4):283-290. doi: 10.1016/j.biopsych.2022.01.007. Epub 2022 Jan 24.

  PMID: 35305821 BACKGROUND

• Debost JPG, Thorsteinsson E, Trabjerg B, Benros ME, Albinana C, Vilhjalmsson BJ, Borglum A, Mors O, Werge T, Mortensen PB, Agerbo E, Petersen LV. Genetic and psychosocial influence on the association between early childhood infections and later psychiatric disorders. Acta Psychiatr Scand. 2022 Nov;146(5):406-419. doi: 10.1111/acps.13491. Epub 2022 Sep 8.

  PMID: 35999619 BACKGROUND

• Benros ME, Waltoft BL, Nordentoft M, Ostergaard SD, Eaton WW, Krogh J, Mortensen PB. Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry. 2013 Aug;70(8):812-20. doi: 10.1001/jamapsychiatry.2013.1111.

  PMID: 23760347 BACKGROUND

• Vai B, Parenti L, Bollettini I, Cara C, Verga C, Melloni E, Mazza E, Poletti S, Colombo C, Benedetti F. Predicting differential diagnosis between bipolar and unipolar depression with multiple kernel learning on multimodal structural neuroimaging. Eur Neuropsychopharmacol. 2020 May;34:28-38. doi: 10.1016/j.euroneuro.2020.03.008. Epub 2020 Mar 29.

  PMID: 32238313 BACKGROUND

• Benros ME, Nielsen PR, Nordentoft M, Eaton WW, Dalton SO, Mortensen PB. Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. Am J Psychiatry. 2011 Dec;168(12):1303-10. doi: 10.1176/appi.ajp.2011.11030516.

  PMID: 22193673 BACKGROUND

• McGrath JJ, Pemberton MR, Welham JL, Murray RM. Schizophrenia and the influenza epidemics of 1954, 1957 and 1959: a southern hemisphere study. Schizophr Res. 1994 Dec;14(1):1-8. doi: 10.1016/0920-9964(94)90002-7.

  PMID: 7893616 BACKGROUND

• Mazza MG, Palladini M, Villa G, Agnoletto E, Harrington Y, Vai B, Benedetti F. Prevalence of depression in SARS-CoV-2 infected patients: An umbrella review of meta-analyses. Gen Hosp Psychiatry. 2023 Jan-Feb;80:17-25. doi: 10.1016/j.genhosppsych.2022.12.002. Epub 2022 Dec 7.

  PMID: 36535239 BACKGROUND

• Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, Melloni EMT, Furlan R, Ciceri F, Rovere-Querini P; COVID-19 BioB Outpatient Clinic Study group; Benedetti F. Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain Behav Immun. 2020 Oct;89:594-600. doi: 10.1016/j.bbi.2020.07.037. Epub 2020 Jul 30.

  PMID: 32738287 BACKGROUND

• Vai B, Mazza MG, Delli Colli C, Foiselle M, Allen B, Benedetti F, Borsini A, Casanova Dias M, Tamouza R, Leboyer M, Benros ME, Branchi I, Fusar-Poli P, De Picker LJ. Mental disorders and risk of COVID-19-related mortality, hospitalisation, and intensive care unit admission: a systematic review and meta-analysis. Lancet Psychiatry. 2021 Sep;8(9):797-812. doi: 10.1016/S2215-0366(21)00232-7. Epub 2021 Jul 17.

  PMID: 34274033 BACKGROUND

• Vai B, Mazza MG, Marisa CD, Beezhold J, Karkkainen H, Saunders J, Samochowiec J, Benedetti F, Leboyer M, Fusar-Poli P, De Picker L. Joint European policy on the COVID-19 risks for people with mental disorders: An umbrella review and evidence- and consensus-based recommendations for mental and public health. Eur Psychiatry. 2022 Aug 16;65(1):e47. doi: 10.1192/j.eurpsy.2022.2307.

  PMID: 35971656 BACKGROUND

• De Picker LJ, Victoriano GM, Richards R, Gorvett AJ, Lyons S, Buckland GR, Tofani T, Norman JL, Chatelet DS, Nicoll JAR, Boche D. Immune environment of the brain in schizophrenia and during the psychotic episode: A human post-mortem study. Brain Behav Immun. 2021 Oct;97:319-327. doi: 10.1016/j.bbi.2021.07.017. Epub 2021 Jul 30.

  PMID: 34339805 BACKGROUND

• Tzur Bitan D, Krieger I, Kridin K, Komantscher D, Scheinman Y, Weinstein O, Cohen AD, Cicurel AA, Feingold D. COVID-19 Prevalence and Mortality Among Schizophrenia Patients: A Large-Scale Retrospective Cohort Study. Schizophr Bull. 2021 Aug 21;47(5):1211-1217. doi: 10.1093/schbul/sbab012.

  PMID: 33604657 BACKGROUND

• Mazza MG, Palladini M, De Lorenzo R, Bravi B, Poletti S, Furlan R, Ciceri F; COVID-19 BioB Outpatient Clinic Study group; Rovere-Querini P, Benedetti F. One-year mental health outcomes in a cohort of COVID-19 survivors. J Psychiatr Res. 2022 Jan;145:118-124. doi: 10.1016/j.jpsychires.2021.11.031. Epub 2021 Nov 22.

  PMID: 34894521 BACKGROUND

• Poletti S, Vai B, Mazza MG, Zanardi R, Lorenzi C, Calesella F, Cazzetta S, Branchi I, Colombo C, Furlan R, Benedetti F. A peripheral inflammatory signature discriminates bipolar from unipolar depression: A machine learning approach. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110136. doi: 10.1016/j.pnpbp.2020.110136. Epub 2020 Oct 9.

  PMID: 33045321 BACKGROUND

• Poletti S, de Wit H, Mazza E, Wijkhuijs AJM, Locatelli C, Aggio V, Colombo C, Benedetti F, Drexhage HA. Th17 cells correlate positively to the structural and functional integrity of the brain in bipolar depression and healthy controls. Brain Behav Immun. 2017 Mar;61:317-325. doi: 10.1016/j.bbi.2016.12.020. Epub 2016 Dec 23.

  PMID: 28025071 BACKGROUND

• Poletti S, Leone G, Hoogenboezem TA, Ghiglino D, Vai B, de Wit H, Wijkhuijs AJM, Locatelli C, Colombo C, Drexhage HA, Benedetti F. Markers of neuroinflammation influence measures of cortical thickness in bipolar depression. Psychiatry Res Neuroimaging. 2019 Mar 30;285:64-66. doi: 10.1016/j.pscychresns.2019.01.009. Epub 2019 Jan 29.

  PMID: 30785023 BACKGROUND

• Benedetti F, Palladini M, Paolini M, Melloni E, Vai B, De Lorenzo R, Furlan R, Rovere-Querini P, Falini A, Mazza MG. Brain correlates of depression, post-traumatic distress, and inflammatory biomarkers in COVID-19 survivors: A multimodal magnetic resonance imaging study. Brain Behav Immun Health. 2021 Dec;18:100387. doi: 10.1016/j.bbih.2021.100387. Epub 2021 Nov 2.

  PMID: 34746876 BACKGROUND

• Tzur Bitan D, Kridin K, Cohen AD, Weinstein O. COVID-19 hospitalisation, mortality, vaccination, and postvaccination trends among people with schizophrenia in Israel: a longitudinal cohort study. Lancet Psychiatry. 2021 Oct;8(10):901-908. doi: 10.1016/S2215-0366(21)00256-X. Epub 2021 Aug 6.

  PMID: 34364406 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood samples

MeSH Terms

Conditions

Mental Disorders; Inflammation; Virus Diseases; Mood Disorders; Schizophrenia

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Schizophrenia Spectrum and Other Psychotic Disorders

Study Officials

• Sara Poletti, PhD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 25, 2025
• Study Start: May 2, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); BE (1); IL (1); IT (1)