Deconstructing Pretest Risk Enrichment to Optimize Prediction of Psychosis in Individuals at Clinical High Risk

Fusar‐Poli, Paolo; Rutigliano, Grazia; Ståhl, Daniel; Schmidt, André; Ramella-Cravaro, Valentina; Shetty, Hitesh; McGuire, Philip

doi:10.1001/jamapsychiatry.2016.2707

Cited by 110 publications

(132 citation statements)

References 52 publications

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“…Secondly, the ultra-high-risk state is intrinsically heterogeneous 10,115 , including different subgroups 115 and varying diagnostic operationalizations 116 . Furthermore, from an epidemiological perspective, it is a spurious condition, characterized by the accumulation of a number of risk factors 117 which enrich the risk in an uncontrolled manner [118][119][120][121][122] . Ethnic minority status and urbanicity may better represent true risk factors, contributing to the development of psychotic disorders through increased socio-environmental adversities 123 .…”

Section: Discussionmentioning

confidence: 99%

What causes psychosis? An umbrella review of risk and protective factors

et al. 2018

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Psychosis is a heterogeneous psychiatric condition for which a multitude of risk and protective factors have been suggested. This umbrella review aimed to classify the strength of evidence for the associations between each factor and psychotic disorders whilst controlling for several biases. The Web of Knowledge database was searched to identify systematic reviews and meta-analyses of observational studies which examined associations between socio-demographic, parental, perinatal, later factors or antecedents and psychotic disorders, and which included a comparison group of healthy controls, published from 1965 to January 31, 2017. The literature search and data extraction followed PRISMA and MOOSE guidelines. The association between each factor and ICD or DSM diagnoses of non-organic psychotic disorders was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of psychotic cases, random-effects p value, largest study 95% confidence interval, heterogeneity between studies, 95% prediction interval, small study effect, and excess significance bias. In order to assess evidence for temporality of association, we also conducted sensitivity analyses restricted to data from prospective studies. Fifty-five meta-analyses or systematic reviews were included in the umbrella review, corresponding to 683 individual studies and 170 putative risk or protective factors for psychotic disorders. Only the ultra-high-risk state for psychosis (odds ratio, OR59.32, 95% CI: 4.91-17.72) and Black-Caribbean ethnicity in England (OR54.87, 95% CI: 3.96-6.00) showed convincing evidence of association. Six factors were highly suggestive (ethnic minority in low ethnic density area, second generation immigrants, trait anhedonia, premorbid IQ, minor physical anomalies, and olfactory identification ability), and nine were suggestive (urbanicity, ethnic minority in high ethnic density area, first generation immigrants, North-African immigrants in Europe, winter/spring season of birth in Northern hemisphere, childhood social withdrawal, childhood trauma, Toxoplasma gondii IgG, and non-right handedness). When only prospective studies were considered, the evidence was convincing for ultra-high-risk state and suggestive for urbanicity only. In summary, this umbrella review found several factors to be associated with psychotic disorders with different levels of evidence. These risk or protective factors represent a starting point for further etiopathological research and for the improvement of the prediction of psychosis.

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Section: Discussionmentioning

confidence: 99%

What causes psychosis? An umbrella review of risk and protective factors

et al. 2018

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“…For example, applying CHR-P criteria to samples with a lower pretest risk of psychosis 9 may substantially dilute the prognostic accuracy of the paradigm and eventually lead to negative findings in the research studies (eg, Klauser et al 10 ; see also table 2 in the study 5 for more examples). Within help-seeking individuals undergoing CHR-P assessment, the pretest risk of psychosis is substantial (15 of 26 [58%]) 11 and heterogeneous (95% CI 9%-24%). 7 It is thus crucial to understand the factors that may modulate it.…”

Section: Risk Enrichment and The Impact Of Recruitment Strategiesmentioning

confidence: 99%

The Clinical High-Risk State for Psychosis (CHR-P), Version II

Fusar‐Poli

2017

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The Clinical High-Risk state for psychosis (CHR-P) paradigm was introduced about 2 decades ago. Over this period of time accumulating knowledge has been gained. Conceptual advancements involve new knowledge into risk enrichment and the impact of recruitment strategies, specificity for prediction of psychotic and nonpsychotic mental disorders and heterogeneity of psychosis risk among the different CHR-P subgroups. The current special issue advances current knowledge on deconstructing the CHR-P paradigm across its 3 subgroups: genetic risk, attenuated psychotic symptoms, and short-lived and remitting psychotic episodes. A conceptual revision of the paradigm (Version II) is suggested and supported by 3 original studies published in this special issue.

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“…Pretest risk enrichment is modulated by the type of recruitment strategies adopted to select individuals for UHR assessment 4 . For example, recruiting individuals who were already filtered by adult mental health services is associated with higher pretest risk enrichment, as compared to recruiting individuals through intensive community outreach 5 . Not surprisingly, the lowest transition risk was reported in McFarlane et al, that has adopted a strong "community outreach and education program aimed at teachers, school, and college counsellors" 3 .…”

Section: Dear Editormentioning

confidence: 99%

“…It therefore seems expedient to control the pretest risk enrichment of samples recruited into future interventional studies for psychosis prevention by using pretest risk stratification models that have been recently validated in this journal 5 .…”

Section: Dear Editormentioning

confidence: 99%

Negative Psychosis Prevention Trials

Fusar‐Poli

2017

JAMA Psychiatry

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To the Editor In the wake of the recently published ω-3 polyunsaturated fatty acids multisite trial (NEURAPRO) by McGorry et al 1 in JAMA Psychiatry (n = 304), the 3 largest studies of preventive interventions in individuals at ultrahigh risk (UHR) for psychosis have turned out to be negative (Morrison et al, 2 n = 288; McFarlane et al, 3 n = 292), suggesting that it may not currently be possible to prevent psychosis. However, the actual risk for psychosis in these interventional studies was found to be extremely low, even in the control group (11.2% in the McGorry et al 1 study at 1 year, 9% at 2 years in the Morrison et al 2 study, and 2.3% at 2 years in the McFarlane et al 3 study), implying that these negative findings are likely to be secondary to small statistical power.On a conceptual level, these studies challenge the underlying assumption that it is acceptable to meet specific psychometric criteria at intake to be slotted into the UHR category. Actually, the predictive power of the UHR criteria is not fixed priority, but is dependent on the risk enrichment of the samples to which they are applied (ie, "pretest" risk). 4 This is owing to the psychometric characteristics of these UHR instruments: they are good to rule out psychosis but only moderately useful to rule in psychosis. 4 Therefore, most of the observed risk for psychosis is not gained through UHR assessment per se, but is obtained before the assessment (pretest phase) during the recruitment of these individuals. Pretest risk enrichment in those undergoing a UHR assessment remains substantial (15% at 38 months) and highly heterogeneous (9%-24% at 38 months). 4 Pretest risk enrichment is modulated by the type of recruitment strategies adopted to select individuals for UHR assessment. 4 For example, recruiting individuals who were already filtered by adult mental health services is associated with higher pretest risk enrichment, as compared with recruiting individuals through intensive community outreach. 5 Not surprisingly, the lowest transition risk was reported in the study by McFarlane et al, 3 which has adopted a "community outreach and education program targeted to teachers, school, and college counsellors." Owing to the heightened pressure to recruit participants into interventional studies, it is possible that a substantial proportion of these samples had been recruited through community outreach, diluting the transition risks.Therefore, it seems expedient to control the pretest risk enrichment of samples recruited into future interventional studies for psychosis prevention by using pretest risk stratification models that have been recently validated in this journal. 5

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Deconstructing Pretest Risk Enrichment to Optimize Prediction of Psychosis in Individuals at Clinical High Risk

Cited by 110 publications

References 52 publications

What causes psychosis? An umbrella review of risk and protective factors

What causes psychosis? An umbrella review of risk and protective factors

The Clinical High-Risk State for Psychosis (CHR-P), Version II

Negative Psychosis Prevention Trials

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