An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

Marco Solmi^#^{1

2

3

4

5}, Samuele Cortese^#^{6

7

8

9

10

11}, Giovanni Vita^#¹², Michele De Prisco^#^{13

14

15}, Joaquim Radua¹⁶, Elena Dragioti^{17

18}, Ole Köhler-Forsberg^{19

20}, Nanna M Madsen^{19

20}, Christopher Rohde^{20

21}, Luis Eudave²², Claudia Aymerich²³, Borja Pedruzo²⁴, Victoria Rodriguez²⁵, Stella Rosson²⁶, Michel Sabé²⁷, Mikkel Hojlund^{28

29

30}, Ana Catalan²³, Beatrice de Luca¹², Michele Fornaro³¹, Giovanni Ostuzzi¹², Corrado Barbui¹², Gonzalo Salazar-de-Pablo^{32

33

34}, Paolo Fusar-Poli^{25

35

36

37}, Christoph U Correll^{38

39

40

41}

Affiliations

¹ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.
² Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
³ On Track: The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ottawa, ON, Canada.
⁴ Ottawa Hospital Research Institute (OHRI) Clinical Epidemiology Program University of Ottawa, Ottawa, ON, Canada.
⁵ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁶ Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
⁷ Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.
⁸ Solent NHS Trust, Southampton, UK.
⁹ Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA.
¹⁰ Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.
¹¹ DiMePRe-J-Department of Precision and Regenerative Medicine-Jonic Area, University of Bari "Aldo Moro", Bari, Italy.
¹² WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.
¹³ Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, 08036, Barcelona, Spain.
¹⁴ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036, Barcelona, Spain.
¹⁵ Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
¹⁶ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Imaging of Mood- and Anxiety-Related Disorders (IMARD), CIBERSAM, University of Barcelona, Barcelona, Spain.
¹⁷ University of Ioannina, Research Laboratory Psychology of Patients, Families & Health Professionals, Department of Nursing, School of Health Sciences, Ioannina, Greece.
¹⁸ Linköping University, Pain and Rehabilitation Centre and Department of Health, Medicine and Caring Sciences, Linköping, Sweden.
¹⁹ Psychosis Research Unit, Aarhus University Hospital Psychiatry, Aarhus, Denmark.
²⁰ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
²¹ Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
²² Faculty of Education and Psychology, University of Navarra, Pamplona, Spain.
²³ Biobizkaia Health Research Institute, Basurto University Hospital, OSI Bilbao-Basurto. University of the Basque Country UPV/EHU. Centro de Investigación en Red de Salud Mental. (CIBERSAM), Instituto de Salud Carlos III. Plaza de Cruces 12, 48903, Barakaldo, Bizkaia, Spain.
²⁴ Psychiatry Department, Basurto University Hospital, Bilbao, Spain.
²⁵ Department of Psychosis Studies, King's College London, London, UK.
²⁶ Mental Health Department, Local Health Unit ULSS3 Serenissima, Venice, Italy.
²⁷ Division of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, 2, Chemin du Petit-Bel-Air, CH-1226, Thonex, Switzerland.
²⁸ Department of Psychiatry Aabenraa, Mental Health Services Region of Southern Denmark, Aabenraa, Denmark.
²⁹ Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.
³⁰ Child and Adolescent Mental Health Centre, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark.
³¹ Department of Psychiatry, Federico II of Naples, Naples, Italy.
³² Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
³³ Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK.
³⁴ Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid, Spain.
³⁵ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
³⁶ Outreach and Support in South London (OASIS) service, NHS South London and Maudsley Foundation Trust, London, UK.
³⁷ Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.
³⁸ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany. christoph.correll@charite.de.
³⁹ The Zucker Hillside Hospital, Northwell Health, New York, NY, USA. christoph.correll@charite.de.
⁴⁰ Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA. christoph.correll@charite.de.
⁴¹ The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Manhasset, NY, USA. christoph.correll@charite.de.

^# Contributed equally.

PMID: 37957292
PMCID: PMC10730397
DOI: 10.1038/s41380-023-02298-3

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

Marco Solmi et al. Mol Psychiatry. 2023 Sep.

. 2023 Sep;28(9):3671-3687.

doi: 10.1038/s41380-023-02298-3. Epub 2023 Nov 13.

Authors

Affiliations

¹ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.
² Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
³ On Track: The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ottawa, ON, Canada.
⁴ Ottawa Hospital Research Institute (OHRI) Clinical Epidemiology Program University of Ottawa, Ottawa, ON, Canada.
⁵ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁶ Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
⁷ Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.
⁸ Solent NHS Trust, Southampton, UK.
⁹ Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA.
¹⁰ Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.
¹¹ DiMePRe-J-Department of Precision and Regenerative Medicine-Jonic Area, University of Bari "Aldo Moro", Bari, Italy.
¹² WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine, and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.
¹³ Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, 08036, Barcelona, Spain.
¹⁴ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, 08036, Barcelona, Spain.
¹⁵ Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
¹⁶ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Imaging of Mood- and Anxiety-Related Disorders (IMARD), CIBERSAM, University of Barcelona, Barcelona, Spain.
¹⁷ University of Ioannina, Research Laboratory Psychology of Patients, Families & Health Professionals, Department of Nursing, School of Health Sciences, Ioannina, Greece.
¹⁸ Linköping University, Pain and Rehabilitation Centre and Department of Health, Medicine and Caring Sciences, Linköping, Sweden.
¹⁹ Psychosis Research Unit, Aarhus University Hospital Psychiatry, Aarhus, Denmark.
²⁰ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
²¹ Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
²² Faculty of Education and Psychology, University of Navarra, Pamplona, Spain.
²³ Biobizkaia Health Research Institute, Basurto University Hospital, OSI Bilbao-Basurto. University of the Basque Country UPV/EHU. Centro de Investigación en Red de Salud Mental. (CIBERSAM), Instituto de Salud Carlos III. Plaza de Cruces 12, 48903, Barakaldo, Bizkaia, Spain.
²⁴ Psychiatry Department, Basurto University Hospital, Bilbao, Spain.
²⁵ Department of Psychosis Studies, King's College London, London, UK.
²⁶ Mental Health Department, Local Health Unit ULSS3 Serenissima, Venice, Italy.
²⁷ Division of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, 2, Chemin du Petit-Bel-Air, CH-1226, Thonex, Switzerland.
²⁸ Department of Psychiatry Aabenraa, Mental Health Services Region of Southern Denmark, Aabenraa, Denmark.
²⁹ Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.
³⁰ Child and Adolescent Mental Health Centre, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark.
³¹ Department of Psychiatry, Federico II of Naples, Naples, Italy.
³² Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
³³ Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK.
³⁴ Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid, Spain.
³⁵ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
³⁶ Outreach and Support in South London (OASIS) service, NHS South London and Maudsley Foundation Trust, London, UK.
³⁷ Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.
³⁸ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany. christoph.correll@charite.de.
³⁹ The Zucker Hillside Hospital, Northwell Health, New York, NY, USA. christoph.correll@charite.de.
⁴⁰ Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA. christoph.correll@charite.de.
⁴¹ The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Manhasset, NY, USA. christoph.correll@charite.de.

^# Contributed equally.

PMID: 37957292
PMCID: PMC10730397
DOI: 10.1038/s41380-023-02298-3

Abstract

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.

PubMed Disclaimer

Conflict of interest statement

CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. CR received the 2020 Lundbeck Foundation Talent Prize. OK-F received honoraria for lectures for Lundbeck Pharma A/S and consultant work for WCG Clinical. MH has been consultant for or has received honoraria from: H. Lundbeck, The Lundbeck Foundation and Otsuka. MS received honoraria/has been a consultant for AbbVie, Angelini, Lundbeck, Otsuka. All other authors declare no conflict of interest.

Figures

**Fig. 1. Study selection flow-chart.**
Screening procedure from title/abstract screening to final inclusion of eligible reviews.

**Fig. 2. Risk of bias of published predictors models of response, remission, recovery, and relapse across mental disorders, according to PROBAST.**
The risk of bias of models included in this review is described across the four PROBAST domains. PROBAST Prediction model Risk Of Bias Assessment Tool.

See this image and copyright information in PMC

References

1. Solmi M, Radua J, Olivola M, Croce E, Soardo L, Salazar de Pablo G, et al. Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies. Mol Psychiatry. 2021;27:281–95. - PMC - PubMed
1. Correll CU, Solmi M, Croatto G, Schneider LK, Rohani-Montez SC, Fairley L, et al. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 2022;21:248–71. - PMC - PubMed
1. Solmi M, Taipale H, Holm M, Tanskanen A, Mittendorfer-Rutz E, Correll CU, et al. Effectiveness of antipsychotic use for reducing risk of work disability: results from a within-subject analysis of a Swedish National Cohort of 21,551 patients with first-episode nonaffective psychosis. Am J Psychiatry. 2022;179:938–46. - PubMed
1. Leucht S, Leucht C, Huhn M, Chaimani A, Mavridis D, Helfer B, et al. Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry. 2017;174:927–42. - PubMed
1. Jääskeläinen E, Juola P, Hirvonen N, McGrath JJ, Saha S, Isohanni M, et al. A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull. 2013;39:1296–306. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

Affiliations

An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous