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Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas

Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas
Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer­tain. We conducted a “meta-umbrella” systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non-purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta-analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta-analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non-organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four-five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention-deficit/hyperactivity disorder (ADHD), they were maternal pre-pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer’s disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I-III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence-based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.

Risk factors, attention-deficit/hyperactivity disorder, autism spectrum disorder, dementia, early intervention, mental disorders, mood disorders, preventive strategies, protective factors, psychotic disorders
1723-8617
417-436
Arango, Celso
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Dragioti, Elena
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Solmi, Marco
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Cortese, Samuele
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Domschke, Katharina
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Murray, Robin M.
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Jones, Peter B.
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Uher, Rudolf
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Carvalho, Andre F.
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Reichenberg, Abraham
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Shin, Jae Ii
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Andreassen, Ole A.
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Correll, Christoph U.
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Fusar‐poli, Paolo
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Arango, Celso
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Dragioti, Elena
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Solmi, Marco
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Cortese, Samuele
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Domschke, Katharina
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Murray, Robin M.
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Jones, Peter B.
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Uher, Rudolf
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Carvalho, Andre F.
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Reichenberg, Abraham
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Shin, Jae Ii
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Andreassen, Ole A.
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Correll, Christoph U.
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Fusar‐poli, Paolo
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Arango, Celso, Dragioti, Elena, Solmi, Marco, Cortese, Samuele, Domschke, Katharina, Murray, Robin M., Jones, Peter B., Uher, Rudolf, Carvalho, Andre F., Reichenberg, Abraham, Shin, Jae Ii, Andreassen, Ole A., Correll, Christoph U. and Fusar‐poli, Paolo (2021) Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas. World Psychiatry, 20 (3), 417-436. (doi:10.1002/wps.20894).

Record type: Article

Abstract

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer­tain. We conducted a “meta-umbrella” systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non-purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta-analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta-analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non-organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four-five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention-deficit/hyperactivity disorder (ADHD), they were maternal pre-pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer’s disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I-III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence-based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.

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Published date: 1 October 2021
Additional Information: Publisher Copyright: © 2021 World Psychiatric Association Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: Risk factors, attention-deficit/hyperactivity disorder, autism spectrum disorder, dementia, early intervention, mental disorders, mood disorders, preventive strategies, protective factors, psychotic disorders

Identifiers

Local EPrints ID: 451772
URI: http://eprints.soton.ac.uk/id/eprint/451772
ISSN: 1723-8617
PURE UUID: be82d9e9-56d6-4206-9823-b185a6502a5b
ORCID for Samuele Cortese: ORCID iD orcid.org/0000-0001-5877-8075

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Date deposited: 26 Oct 2021 16:34
Last modified: 17 Mar 2024 03:37

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Contributors

Author: Celso Arango
Author: Elena Dragioti
Author: Marco Solmi
Author: Samuele Cortese ORCID iD
Author: Katharina Domschke
Author: Robin M. Murray
Author: Peter B. Jones
Author: Rudolf Uher
Author: Andre F. Carvalho
Author: Abraham Reichenberg
Author: Jae Ii Shin
Author: Ole A. Andreassen
Author: Christoph U. Correll
Author: Paolo Fusar‐poli

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