Observational Study
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World J Psychiatry. Mar 19, 2022; 12(3): 425-449
Published online Mar 19, 2022. doi: 10.5498/wjp.v12.i3.425
Clinical high-risk criteria of psychosis in 8–17-year-old community subjects and inpatients not suspected of developing psychosis
Frauke Schultze-Lutter, Petra Walger, Maurizia Franscini, Nina Traber-Walker, Naweed Osman, Helene Walger, Benno G Schimmelmann, Rahel Flückiger, Chantal Michel
Frauke Schultze-Lutter, Petra Walger, Naweed Osman, Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf 40629, North-Rhine Westphalia, Germany
Frauke Schultze-Lutter, Department of Psychology, Faculty of Psychology, Airlangga University, Surabaya 60286, Indonesia
Frauke Schultze-Lutter, Benno G Schimmelmann, Rahel Flückiger, Chantal Michel, University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern 3000, Switzerland
Maurizia Franscini, Nina Traber-Walker, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Zürich, Zürich 8032, Germany
Helene Walger, Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich 80336, Bavaria, Germany
Benno G Schimmelmann, University Hospital of Child and Adolescent Psychiatry, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
Author contributions: Schultze-Lutter F and Schimmelmann BG designed the study; Walger P, Franscini M, Traber-Walker N, Flückiger R and Michel C were involved in the acquisition of data; Schultze-Lutter F and Michel C analyzed and interpreted the data for the work and drafted the first version of this work; all authors revised the article critically for important intellectual content, and agreed to the submitted version.
Supported by the conjoint research grant of the Swiss National Science Foundation, SNSF, No. 144100; and the German Research Foundation, DFG, No. 231563730, within the Lead Agency Process (SNSF as exclusive evaluating and approving lead agency).
Institutional review board statement: The study was reviewed and approved by the Kantonale Ethikkommission Bern, the Institutional Review Board of the University of Bern (No. 174/10), the Kantonale Ethik-Kommission Zürich, the Institutional Review Board of the University of Zurich (No. 2010-0415/3), and the Ethikkommision Köln, the Institutional Review Board of the Medical Faculty of the University of Cologne (No. 11-071).
Informed consent statement: All study participants, and their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Schimmelmann BG received honoraria for presentations by Takeda and InfectoPharm outside the reported work. All other authors reported no conflict of interest.
Data sharing statement: Data is available upon reasonable request for clearly defined scientific purposes from the corresponding author at frauke.schultze-lutter@lvr.de. Participants of the BEARS-Kid study gave informed consent for sharing of anonymized data.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Frauke Schultze-Lutter, MSc, PhD, Assistant Professor, Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Bergische Landstraße 2, Düsseldorf 40629, North-Rhine Westphalia, Germany. frauke.schultze-lutter@lvr.de
Received: April 14, 2021
Peer-review started: April 14, 2021
First decision: July 14, 2021
Revised: July 26, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: March 19, 2022
Processing time: 337 Days and 23.3 Hours
ARTICLE HIGHLIGHTS
Research background

Many patients with clinical high-risk of psychosis (CHR) criteria do not develop psychosis, in particular if they are still in their childhood and adolescence. Therefore, CHR criteria were suggested to be not a risk indicator of psychosis development but (1) A pluripotential syndrome that will transform itself into all kinds of mental disorder; (2) A transdiagnostic risk factor from that all kind of different disorders develop; or (3) Simply a severity marker of mental disorders.

Research motivation

The simple nonconversion to psychosis and the persistence or new-occurrence rate of nonpsychotic mental disorders in CHR samples, however, do not allow for the conclusion of any of the three alternative explanatory models, which might explain why they are often proposed interchangeably. Thus, to gain more insight into the nature of CHR symptoms and criteria, we examined the differential implications that each of these models has on the occurrence of CHR criteria and symptoms and their association with a proxy measure of illness severity in patients with severe mental disorders; i.e., inpatients and community subjects. We expected that any pattern of group differences indicative of one of the alternative explanatory models should become particularly apparent in a child and adolescent sample, as CHR symptoms and criteria were reported to be more frequent but less clinically relevant and less associated with psychosis in children and adolescents compared to adults.

Research objectives

Following a propositional logic approach, we examined which of the three alternative explanatory models of CHR criteria and symptoms would best fit our data. The three alternative explanatory models were associated with the following differential premises with respect to the data: (1) If CHR criteria and symptoms are more frequent in community subjects compared to inpatients, then they are likely pluripotential. This has been assumed because a pluripotent syndrome would have transformed into a mental disorder and, thus, not be present in inpatients, but in a community sample wherein a proportion can be expected to develop a mental disorder in future; (2) If CHR criteria and symptoms are more frequent in inpatients compared to community subjects, then they likely represent a transdiagnostic risk factor or dimension. This has been assumed because they would aggregate in persons with mental illness; and (3) If CHR criteria and symptoms show a clinically relevant, significant negative correlation with functioning as a proxy measure of illness severity, then they likely represent a severity marker of psychopathology.

Research methods

As part of the Bi-national Evaluation of At-Risk Symptoms in children and adolescents (BEARS-Kid) study, we cross-sectionally examined the frequency and severity of CHR criteria and symptoms in an 8–17-year-old randomly recruited sample of the Swiss community (n = 233) and in 8–17-year-old inpatients (n = 306) whose main diagnosis was a disorder that, earlier, had been associated with an elevated risk for psychosis in adulthood (obsessive compulsive and anxiety, attention deficit, eating, and autism-spectrum disorder) using χ2 and nonparametric analyses. Furthermore, the associations between psychosocial functioning, and CHR criteria and symptoms were analyzed with bivariate and partial correlation analyses, the latter controlling for group membership. CHR criteria and symptoms according to the ultra-high risk and the basic symptom approach were assessed in clinical interviews by trained psychologists using the Structured Interview for Psychosis-Risk Syndromes (SIPS) and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY). Furthermore, we followed up 78.5% of the participants after 1 year, and 61.4% after 2 years past baseline for a conversion to psychosis.

Research results

The 7.3% prevalence rate of CHR criteria in community subjects did not differ significantly from the 9.5% rate in inpatients. Frequency and severity of CHR criteria never differed between the community and the four inpatient groups. The frequency and severity of CHR symptoms differed between the community and the four inpatient groups only in four CHR symptoms: suspiciousness/persecutory ideas of the SIPS as well as thought pressure, derealization and visual perception disturbances of the SPI-CY. The persistent pattern of these differences was consistent with a transdiagnostic risk factor or dimension; i.e., these symptoms were more frequent and severe in inpatients, in particular in those with eating, anxiety/obsessive–compulsive and autism-spectrum disorders. Furthermore, low functioning was – if at all – at most weakly related to the severity of CHR criteria and symptoms; the highest, yet weak correlation was for suspiciousness/persecutory ideas. Four participants had developed a psychotic disorder within two years past baseline. In doing so, the 2-year conversion rate in participants with CHR criteria was 11.5% and, the comparison of the conversion rate in participants with and without CHR criteria at baseline exhibited the highest, near moderate effect size of all comparisons.

Research conclusions

This study was the first to systematically study alternative explanatory models for current CHR states, which propose that CHR criteria and symptoms would represent a pluripotent syndrome, a transdiagnostic risk factor or dimension, or even merely a marker for the severity of any mental disorder. The general lack of systematic differences in the frequency and severity of CHR criteria and symptoms between inpatients and community subjects, and the lack of a sufficiently strong association between functioning, and CHR criteria and symptoms did not support any of these alternative explanatory models. Rather, the strongest, though still only moderate effect was found for the association of CHR criteria and the subsequent development of a psychotic disorder within two years. This association, however, appears not strong enough to conclusively explain the role of CHR criteria and symptoms in children and adolescents by their psychosis-predictive potential. Thus, overall, our results more clearly indicate what CHR symptoms and criteria are not rather than indicating what they are.

Only four CHR symptoms – suspiciousness/persecutory ideas of the SIPS, and thought pressure, derealization and visual perception disturbances of the SPI-CY – exhibited a pattern of group differences indicative of a transdiagnostic risk factor, in particular with respect to eating, autism-spectrum, and anxiety and obsessive–compulsive disorders. Thus, their inclusion and definition in current CHR criteria should be critically examined in future studies.

Research perspectives

Our results add to the growing support of the view that CHR criteria should be regarded as a self-contained disorder or syndrome. To more fully test this assumption, future community studies should evaluate the effect of CHR criteria on help seeking and mental wellbeing. If persons meeting CHR criteria generally suffer from their CHR symptoms, seek help for them, and/or experience disturbances in psychosocial functioning irrespective of, or in addition to, the effects of any other potential comorbid mental disorder, CHR criteria would fulfil general criteria for mental disorders in terms of a CHR Syndrome. Thus, further research on CHR symptoms and criteria, and their cause and meaning in children and adolescents is needed to better understand their significance in this age group, and to detect factors that convey their higher clinical relevance in adulthood.