Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk

Fusar‐Poli, Paolo; Cappucciati, Marco; Borgwardt, Stefan; Woods, Scott W.; Addington, Jean; Nelson, Barnaby; Nieman, Dorien H.; Ståhl, Daniel; Rutigliano, Grazia; Riecher-Rössler, Anita; Simon, Andor E.; Mizuno, Masafumi; Lee, Tae Young; Kwon, Jun Soo; Lam, May M.L.; Pérez, Jesús; Kéri, Szabolcs; Amminger, G. Paul; Metzler, Sibylle; Kawohl, Wolfram; Rössler, Wulf; Lee, Jimmy; Labad, Javier; Ziermans, Tim; An, Suk Kyoon; Liu, Chen-Chung; Woodberry, Kristen A.; Braham, A.; Corcoran, Cheryl; McGorry, Patrick D.; Yung, Alison R.; McGuire, Philip

doi:10.1001/jamapsychiatry.2015.2324

Cited by 356 publications

(317 citation statements)

References 57 publications

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“…Based on the criteria applied in our study we would, for example, expect our ARMS cohort to mainly comprise individuals with attenuated psychotic symptoms. 58 Although the reasons for this divergence remain open, our findings question grey matter volume decreases as a common biomarker in FEP and ARMS populations, suggesting grey matter volume increases also exist in these patient cohorts. Regions showing interactions with age in our study cover an extensive anatomic network overlapping most of the regions also showing an increased grey matter volume in group comparisons.…”

Section: Discussionmentioning

confidence: 65%

Age-related brain structural alterations as an intermediate phenotype of psychosis

Dukart

Smieskova

Harrisberger

et al. 2017

JPN

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Section: Discussionmentioning

confidence: 65%

Age-related brain structural alterations as an intermediate phenotype of psychosis

Dukart

Smieskova

Harrisberger

et al. 2017

JPN

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“…Indeed, some ultra-highrisk individuals already present with severe symptoms, including short-lived psychotic episodes 111,112 , affective symptoms 113 and impaired functioning 114 . 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] .…”

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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“…16 Recent research, however, has suggested that the 3 CHR subgroups may be at different (or mixed) stages of the early illness 17 and each may be associated with different levels of risk, with the GRD subgroup having the lowest risk and BIPS having the highest. 18 In addition, it is unclear whether each of the 3 subgroups has a different pattern of outcome aside from conversion (eg, stage persistence or symptom recovery), and what the implications are for improving the precision and effectiveness of early intervention.…”

Section: Introductionmentioning

confidence: 99%

A Severity-Based Clinical Staging Model for the Psychosis Prodrome: Longitudinal Findings From the New York Recognition and Prevention Program

Carrión

Correll

Auther

et al. 2017

SCHBUL

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Clinical staging improved the possibility of intervening during the psychosis prodrome to limit progression of illness. The current study aimed to validate a novel 4-stage severitybased model with a focus on clinical change over time and risk for conversion to psychosis. One hundred seventy-one individuals at clinical high risk (CHR) for psychosis were followed prospectively (3 ± 1.6 y) as part of the Recognition and Prevention (RAP) program and divided into 4 diagnostic stages according to absence/presence and severity of attenuated positive symptoms. Twenty-two percent of the combined sample recovered (no prodromal symptoms) by study outcome. The negative symptoms only subgroup had the highest symptom stability (70%), but the lowest conversion rate at 5.9%. The subgroup with more severe baseline attenuated positive symptom levels had a higher conversion rate (28%) and a more rapid onset when compared to the moderate attenuated positive symptom subgroup (11%). Finally, the Schizophrenia-Like Psychosis (SLP) subgroup showed low stability (3%), with 49% developing a specific psychotic disorder. The proposed stage model provides a more finely grained classification system than the standard diagnostic approach for prodromal individuals. All 4 stages are in need of early intervention because of low recovery rates. The negative symptom only stage is possibly a separate clinical syndrome, with an increased risk of functional disability. Both subgroups with attenuated positive symptoms are appropriate for studying the mechanisms of psychosis risk, however, individuals with more severe baseline positive symptoms appear better suited to clinical trials. Finally, the SLP category represents an intermediate outcome group appropriate for preventative intervention research but questionable for inclusion in prodromal studies of mechanisms.

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Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk

Cited by 356 publications

References 57 publications

Age-related brain structural alterations as an intermediate phenotype of psychosis

Age-related brain structural alterations as an intermediate phenotype of psychosis

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

A Severity-Based Clinical Staging Model for the Psychosis Prodrome: Longitudinal Findings From the New York Recognition and Prevention Program

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