Predictive Performance of Exposome Score for Schizophrenia in the General Population

Pries, Lotta-Katrin; Erzın, Gamze; Os, Jim van; Have, Margreet ten; Graaf, Ron de; Dorsselaer, Saskia van; Bak, Maarten; Rutten, Bart P. F.; Gülöksüz, Sinan

doi:10.1093/schbul/sbaa170

Cited by 21 publications

(35 citation statements)

References 31 publications

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“…In line with these findings, a recent study found that ES-SCZ was temporally linked to general mental and physical health outcomes in the general population (33). Similarly, another study revealed that ES-SCZ was also associated with increased risk for various mental disorders (e.g., depression, anxiety, and alcohol use disorders), personality traits (i.e., neuroticism and extraversion), and medical complaints including migraine, asthma, and ulcers (30).…”

Section: Is the Exposome Score For Schizophrenia Phenotype-specific?mentioning

confidence: 66%

“…The ES-SCZ was able to discriminate patients with a diagnosis of schizophrenia, their siblings, and healthy controls in the validation dataset. The follow-up study using data from an independent general population cohort likewise revealed that the performance of ES-SCZ for identifying clinical psychosis diagnosis was better than the environmental sum score and the environmental score derived from meta-analytical estimates (30). Furthermore, within a large international sample with patients diagnosed with schizophrenia and healthy controls, the ES-SCZ explained 28% of the variance (Nagelkerke's pseudo R 2 ) in casecontrol status and 33% after adjusting for age, sex, and country, whereas the PRS-SCZ explained 15% (adjusted for 10 principal components) and 20% after additionally adjusting for age, sex, and country (31).…”

Section: Estimating An Aggregate Environmental Risk Score For Schizophreniamentioning

confidence: 99%

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Estimating Aggregate Environmental Risk Score in Psychiatry: The Exposome Score for Schizophrenia

et al. 2021

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To understand the role of environment in the pathoetiology of psychosis spectrum disorders, research has thus far mainly investigated the effects of single exposures in isolation, such as the association between cannabis use and schizophrenia. However, this approach fails to acknowledge the complexity of the exposome, which represents the totality of the environment involving many exposures over an individual's lifetime. Therefore, contemporary research adopting the exposome paradigm has aimed at capturing the combined effect of different environmental exposures by utilizing an aggregate environmental vulnerability score for schizophrenia: the exposome score for schizophrenia. Here, we attempt to provide a comprehensive overview of studies applying the exposome score for schizophrenia. First, we describe several approaches estimating exposomic vulnerability for schizophrenia, which falls into three categories: simple environmental sum scores (sum of dichotomized exposures), meta-analysis-based environmental risk score (sum scores weighted by estimates from meta-analyses), and the exposome score (sum score weighted by estimates from an analysis in an independent training dataset). Studies show that the exposome score for schizophrenia that assumes interdependency of exposures performs better than scores that assume independence of exposures, such as the environmental sum score and the meta-analysis-based environmental risk score. Second, we discuss findings on the pluripotency of the exposome score for schizophrenia and summarize findings from gene-environment studies using the exposome score for schizophrenia. Finally, we discuss possible scientific, clinical, and population-based applications of exposome score for schizophrenia, as well as limitations and future directions for exposome research to understand the etiology of psychosis spectrum disorders.

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Section: Is the Exposome Score For Schizophrenia Phenotype-specific?mentioning

confidence: 66%

Section: Estimating An Aggregate Environmental Risk Score For Schizophreniamentioning

confidence: 99%

Estimating Aggregate Environmental Risk Score in Psychiatry: The Exposome Score for Schizophrenia

et al. 2021

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“…First, environmental factors pose logistic barriers, because their assessment may be particularly time consuming and lead to missing data. Recent developments in digital technologies (e.g., electronic medical records, mobile apps) 87,88 and sequential testing frameworks 89 , as well as the recent availability of polyenvironmental risk scores (e.g., psychosis poly-risk score 87,90 or exposome 91 ), may make it possible to record multiple exposures in the same individuals in a deep phenotyping approach and over time.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer tain. We conducted a "metaumbrella" systematic synthesis of umbrella reviews, which are systematic reviews of metaanalyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on nonpurely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convinc ing), 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 metaanalyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 metaanalyses 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 con tacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For nonorganic 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 fourfive (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 prepregnancy 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 IIII risk/protective factors were mostly involved in the early neurodevelopmental period. The evidencebased atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expand ing early intervention and preventive strategies for mental disorders.

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“…In addition to these individual social risk factors, there is also evidence for an accumulation of risk when multiple social factors are combined ( 44 ), as well as for the impact of accumulating social risk on gene-environment interactions ( 45 ). Environment-gene interactions are now often studied within the relatively new science of epigenetics [for a review of epigenetics in psychosis see ( 46 )].…”

Section: Social Pathways To Psychosismentioning

confidence: 99%

Trauma and Social Pathways to Psychosis, and Where the Two Paths Meet

2022

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The pathways from trauma—via dissociation—to psychosis have been thoroughly tested and evidenced, but what has received less attention has been the social pathways—via dissociation—to psychosis. Often social factors are more commonly linked to other influences, e.g., to appraisals and the creation of negative schema in cognitive models, or to unsupportive caregiving experiences where there is high “expressed emotion.” However, evidence is now emerging that negative social rank experiences, such as being excluded or shamed, may themselves have dissociative properties, which poses intriguing questions as to how trauma pathways and social pathways might interact. This article reviews the state of knowledge in trauma and social pathways to psychosis and then considers the potential mechanisms and the relationships between them, specifically (i) dissociation, (ii) attachment, and (iii) social rank. Recommendations are suggested for future modeling and testing of three-way interactions (dissociation × attachment × social rank) in the pathway from trauma to psychosis.

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Predictive Performance of Exposome Score for Schizophrenia in the General Population

Cited by 21 publications

References 31 publications

Estimating Aggregate Environmental Risk Score in Psychiatry: The Exposome Score for Schizophrenia

Estimating Aggregate Environmental Risk Score in Psychiatry: The Exposome Score for Schizophrenia

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

Trauma and Social Pathways to Psychosis, and Where the Two Paths Meet

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