Published online Mar 19, 2022. doi: 10.5498/wjp.v12.i3.425
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
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.
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.
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.
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.
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.
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.
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.