Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies

Marco Solmi; Elena Dragioti; Celso Arango; Joaquim Radua; Edoardo Ostinelli; Ozge Kilic; Ugur Eser Yilmaz; Merve Yalcinay-İnan; Fernanda Cunha Soares; Luca Mariano; Pierluca Mosillo; Samuele Cortese; Christoph U. Correll; Andre F. Carvalho; Jae Il Shin; Paolo Fusar-Poli

doi:10.1016/j.neubiorev.2020.09.002

Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies

Marco Solmi, Elena Dragioti, Celso Arango, Joaquim Radua, Edoardo Ostinelli, Ozge Kilic, Ugur Eser Yilmaz, Merve Yalcinay-İnan, Fernanda Cunha Soares, Luca Mariano, Pierluca Mosillo, Samuele Cortese, Christoph U. Correll, Andre F. Carvalho, Jae Il Shin, Paolo Fusar-Poli

Department of Pediatrics

Research output: Contribution to journal › Review article › peer-review

9 Citations (Scopus)

Abstract

The patho-etiology of mental disorders with onset in childhood or adolescence remains largely unknown. We conducted an umbrella review of meta-analyses (MAs) on environmental factors associated with mental disorders with onset in childhood/adolescence. We searched Pubmed-MEDLINE/EMBASE/PsycInfo databases, last search April 29th, 2020. Quality of MAs was measured with AMSTAR-2. Out of 6851 initial references, ten articles met inclusion criteria, providing 23 associations between 12 potential environmental factors and nine disorders (cases: 8884; N = 3,660,670). While almost half of the associations were nominally significant, none of them met criteria from either convincing or highly suggestive evidence. A single association was supported by suggestive evidence (maternal exposure to lithium or antipsychotics with neuromotor deficits), but it was affected by confounding by indication. Ten more associations had weak evidence, and 12 associations were not statistically significant. Quality of meta-analyses was rated as high in two, moderate in one, low in four, critically low in two, and not pertinent in one (individual participant data). Methodologically-sound research is needed in this field.

Original language	English
Pages (from-to)	565-573
Number of pages	9
Journal	Neuroscience and Biobehavioral Reviews
Volume	120
DOIs	https://doi.org/10.1016/j.neubiorev.2020.09.002
Publication status	Published - 2021 Jan

Bibliographical note

Funding Information:
CUC has been a consultant and/or advisor to or have received honoraria from: Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma.

Funding Information:
No funding supported the present study, CA is supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1,PI16/02012,PI19/024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz.

Funding Information:
CA is supported by the S panish Ministry of Science and Innovation . Instituto de Salud Carlos III ( SAM16PE07CP1, PI16/02012, PI19/024) , co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916 , Project PRISM, and grant agreement No 777394 , Project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz.

Publisher Copyright:
© 2020 Elsevier Ltd

All Science Journal Classification (ASJC) codes

Neuropsychology and Physiological Psychology
Cognitive Neuroscience
Behavioral Neuroscience

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10.1016/j.neubiorev.2020.09.002

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Solmi, M., Dragioti, E., Arango, C., Radua, J., Ostinelli, E., Kilic, O., Yilmaz, U. E., Yalcinay-İnan, M., Soares, F. C., Mariano, L., Mosillo, P., Cortese, S., Correll, C. U., Carvalho, A. F., Shin, J. I., & Fusar-Poli, P. (2021). Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies. Neuroscience and Biobehavioral Reviews, 120, 565-573. https://doi.org/10.1016/j.neubiorev.2020.09.002

@article{e2af994295b3469abf3749ea31d75b28,

title = "Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies",

abstract = "The patho-etiology of mental disorders with onset in childhood or adolescence remains largely unknown. We conducted an umbrella review of meta-analyses (MAs) on environmental factors associated with mental disorders with onset in childhood/adolescence. We searched Pubmed-MEDLINE/EMBASE/PsycInfo databases, last search April 29th, 2020. Quality of MAs was measured with AMSTAR-2. Out of 6851 initial references, ten articles met inclusion criteria, providing 23 associations between 12 potential environmental factors and nine disorders (cases: 8884; N = 3,660,670). While almost half of the associations were nominally significant, none of them met criteria from either convincing or highly suggestive evidence. A single association was supported by suggestive evidence (maternal exposure to lithium or antipsychotics with neuromotor deficits), but it was affected by confounding by indication. Ten more associations had weak evidence, and 12 associations were not statistically significant. Quality of meta-analyses was rated as high in two, moderate in one, low in four, critically low in two, and not pertinent in one (individual participant data). Methodologically-sound research is needed in this field.",

author = "Marco Solmi and Elena Dragioti and Celso Arango and Joaquim Radua and Edoardo Ostinelli and Ozge Kilic and Yilmaz, {Ugur Eser} and Merve Yalcinay-İnan and Soares, {Fernanda Cunha} and Luca Mariano and Pierluca Mosillo and Samuele Cortese and Correll, {Christoph U.} and Carvalho, {Andre F.} and Shin, {Jae Il} and Paolo Fusar-Poli",

note = "Funding Information: CUC has been a consultant and/or advisor to or have received honoraria from: Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma. Funding Information: No funding supported the present study, CA is supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1,PI16/02012,PI19/024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci{\'o}n Familia Alonso and Fundaci{\'o}n Alicia Koplowitz. Funding Information: CA is supported by the S panish Ministry of Science and Innovation . Instituto de Salud Carlos III ( SAM16PE07CP1, PI16/02012, PI19/024) , co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916 , Project PRISM, and grant agreement No 777394 , Project AIMS-2-TRIALS), Fundaci{\'o}n Familia Alonso and Fundaci{\'o}n Alicia Koplowitz. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2021",

month = jan,

doi = "10.1016/j.neubiorev.2020.09.002",

language = "English",

volume = "120",

pages = "565--573",

journal = "Neuroscience and Biobehavioral Reviews",

issn = "0149-7634",

publisher = "Elsevier Limited",

}

Solmi, M, Dragioti, E, Arango, C, Radua, J, Ostinelli, E, Kilic, O, Yilmaz, UE, Yalcinay-İnan, M, Soares, FC, Mariano, L, Mosillo, P, Cortese, S, Correll, CU, Carvalho, AF, Shin, JI & Fusar-Poli, P 2021, 'Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies', Neuroscience and Biobehavioral Reviews, vol. 120, pp. 565-573. https://doi.org/10.1016/j.neubiorev.2020.09.002

Risk and protective factors for mental disorders with onset in childhood/adolescence : An umbrella review of published meta-analyses of observational longitudinal studies. / Solmi, Marco; Dragioti, Elena; Arango, Celso et al.

In: Neuroscience and Biobehavioral Reviews, Vol. 120, 01.2021, p. 565-573.

Research output: Contribution to journal › Review article › peer-review

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T1 - Risk and protective factors for mental disorders with onset in childhood/adolescence

T2 - An umbrella review of published meta-analyses of observational longitudinal studies

AU - Solmi, Marco

AU - Dragioti, Elena

AU - Arango, Celso

AU - Radua, Joaquim

AU - Ostinelli, Edoardo

AU - Kilic, Ozge

AU - Yilmaz, Ugur Eser

AU - Yalcinay-İnan, Merve

AU - Soares, Fernanda Cunha

AU - Mariano, Luca

AU - Mosillo, Pierluca

AU - Cortese, Samuele

AU - Correll, Christoph U.

AU - Carvalho, Andre F.

AU - Shin, Jae Il

AU - Fusar-Poli, Paolo

N1 - Funding Information: CUC has been a consultant and/or advisor to or have received honoraria from: Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma. Funding Information: No funding supported the present study, CA is supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1,PI16/02012,PI19/024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz. Funding Information: CA is supported by the S panish Ministry of Science and Innovation . Instituto de Salud Carlos III ( SAM16PE07CP1, PI16/02012, PI19/024) , co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916 , Project PRISM, and grant agreement No 777394 , Project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz. Publisher Copyright: © 2020 Elsevier Ltd

PY - 2021/1

Y1 - 2021/1

N2 - The patho-etiology of mental disorders with onset in childhood or adolescence remains largely unknown. We conducted an umbrella review of meta-analyses (MAs) on environmental factors associated with mental disorders with onset in childhood/adolescence. We searched Pubmed-MEDLINE/EMBASE/PsycInfo databases, last search April 29th, 2020. Quality of MAs was measured with AMSTAR-2. Out of 6851 initial references, ten articles met inclusion criteria, providing 23 associations between 12 potential environmental factors and nine disorders (cases: 8884; N = 3,660,670). While almost half of the associations were nominally significant, none of them met criteria from either convincing or highly suggestive evidence. A single association was supported by suggestive evidence (maternal exposure to lithium or antipsychotics with neuromotor deficits), but it was affected by confounding by indication. Ten more associations had weak evidence, and 12 associations were not statistically significant. Quality of meta-analyses was rated as high in two, moderate in one, low in four, critically low in two, and not pertinent in one (individual participant data). Methodologically-sound research is needed in this field.

AB - The patho-etiology of mental disorders with onset in childhood or adolescence remains largely unknown. We conducted an umbrella review of meta-analyses (MAs) on environmental factors associated with mental disorders with onset in childhood/adolescence. We searched Pubmed-MEDLINE/EMBASE/PsycInfo databases, last search April 29th, 2020. Quality of MAs was measured with AMSTAR-2. Out of 6851 initial references, ten articles met inclusion criteria, providing 23 associations between 12 potential environmental factors and nine disorders (cases: 8884; N = 3,660,670). While almost half of the associations were nominally significant, none of them met criteria from either convincing or highly suggestive evidence. A single association was supported by suggestive evidence (maternal exposure to lithium or antipsychotics with neuromotor deficits), but it was affected by confounding by indication. Ten more associations had weak evidence, and 12 associations were not statistically significant. Quality of meta-analyses was rated as high in two, moderate in one, low in four, critically low in two, and not pertinent in one (individual participant data). Methodologically-sound research is needed in this field.

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Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies

Abstract

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