Project

Psychosis; Early Detection; At-Risk Criteria; Children and Adolescents; Predictors

Lead
Psychosen haben eine Lebenszeitprävalenz von etwa 3-3,5%. 10-15% beginnen vor dem 18. Lebensjahr; vorangehende Frühzeichen (Risikokriterien) einer beginnenden Psychose sind entsprechend wohl noch häufiger vor dem 18. Lebensjahr. Für die Früherkennung vor Ausbruch einer Psychose sind im Erwachsenenalter Risikokriterien definiert und validiert worden. Deren Gültigkeit wurde für Kinder und Jugendliche bislang nicht untersucht, obwohl es Hinweise auf entwicklungsbedingte Unterschiede gibt.
Lay summary
Inhalt und Ziel des Forschungsprojekts Die Studie untersucht die Anwendbarkeit der aktuellen Risikokriterien für Psychosen bei Kindern und Jugendlichen. Im Detail werden untersucht (1) die Übergangsrate in eine Psychose innerhalb der Risikogruppe (AtRisk; angestrebtes n=209), (2) die Häufigkeit und Vorhersagekraft einzelner Risikokriterien sowie soziodemographischer, neuropsychologischer, genetischer und Bildgebungs-Prädiktoren, (3) die Häufigkeit von Risikokriterien im Prodrom juveniler Psychosen (EOP; n=100) und (5) die Häufigkeit von Risikokriterien in der Allgemeinbevölkerung (GPS; n=250) und in klinischen Populationen (ClinS; n=264). Die 3-jährige Studie wird in Bern, Zürich und Köln (dort gefördert durch die Deutsche Forschungsgemeinschaft) durchgeführt. Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts Dieses Projekt wird entscheidende Informationen über die Validität der derzeit nur für Erwachsene validierten Psychose-Risikokriterien bei Kindern und Jugendlichen liefern. Die Ergebnisse werden sowohl für das Verständnis der Neurobiologie der Entwicklung einer Psychose als auch für die klinische Früherkennungspraxis von hoher Bedeutung sein.

Direct link to Lay Summary

Last update: 28.01.2013

Active participation

Number	Title	Start	Funding scheme

Background: Psychoses have an incidence of about 3% with a peak of first onset around the age of 20; 10 to 15% have an onset before the age of 18. These ‘early-onset psychoses’ (EOP) are generally considered to have an even poorer prognosis than ‘adult-onset psychoses’ (AOP) that have repeatedly been shown to cause enormous disability and costs. Currently, an early detection of and intervention in persons with first signs of emerging psychosis is regarded a promising strategy to reduce the burden of this disease. To this aim, two complementary sets of at-risk criteria have been developed on mainly adult samples: (1) ‘ultra high risk’ criteria (UHR) including attenuated and brief limited intermittent psychotic symptoms and a combination of a genetic risk factor and a recent significant functional decline and (2) the basic symptom criteria (BS) ‘cognitive-perceptive basic symptoms’ and ‘cognitive disturbances’. To date, prevention research in psychosis has mainly been carried out in adult or mixed-age help-seeking at-risk samples, i.e., including a small fraction of mainly older adolescents. And despite some indications that at-risk criteria perform differently in adolescent samples - not least due to developmental aspects, no study has hitherto systematically examined the clinical validity and predictive value of at-risk criteria or of the currently discussed additional neuropsychological predictors of psychosis in child and adolescent (CAD) samples.Working hypothesis and specific aims: The primary aim is to examine the conversion rate to frank psychosis in an at-risk CAD sample (AtRisk) and thereby the positive predictive power of at-risk criteria. Based on the literature, we expect a lower first-year conversion rate compared to adults (<20%), while the second-year conversion rate (no change, increase or decrease compared the first-year) is unclear. The seven secondary aims are: (1) to assess the prevalence rates of at-risk criteria, and sociodemographic and neuropsychological predictors, proposed to enhance predictive accuracy, and to identify the main predictors of conversion to psychosis in AtRisk. We expect a different set of predictors compared to adults; (2) to explore the risk enhancing properties of genetic polymorphisms; (3) to examine the risk enhancing properties of functional imaging data (in a subsample); (4) to assess the general outcome of AtRisk beyond conversion to psychosis and the role of life events in this; (5) to assess the prevalence of at-risk criteria prior to the onset of psychotic symptoms (in the prodromal phase) in a first admitted EOP sample and thereby the sensitivity of at-risk criteria in CAD. We expect an equal or higher sensitivity in EOP compared to AOP; (6) to assess prevalence rates and distributions of at-risk criteria and additional potential predictors of conversion to psychosis in a general population (GPS) as well as a clinical non-psychotic sample (ClinS) with diagnoses, for which an increased prevalence of subsequent psychosis were reported, allowing for calculation of negative predictive power and specificity estimates; and (7) to explore gender differences in the frequency and distribution of at-risk criteria.Methods: This is a prospective multi-centre naturalistic 3-year follow-up study (Bern, Zurich, Cologne) on altogether 209 AtRisk, 264 ClinS, 250 GPS and 100 EOP. At-risk symptoms and criteria will be assessed with the ‘Structured Interview for Prodromal Syndromes’ and the ‘Schizophrenia Prediction Instrument, Child & Youth version’. Further, sociodemographics and functioning measures, DSM-IV diagnoses as well as potential neuropsychological predictors of conversion (verbal fluency, verbal and working memory as well as processing speed) will be assessed. AtRisk and ClinS will be recruited over 2 years and followed annually at year 1 and 2, GPS will be recruited in year 1 and followed annually at year 1 and 2. Beyond the funded study period, all participating centres have agreed to further follow-up AtRisk until 5-year follow-up as in-house contributions. Repeated collection of saliva samples will allow genetic/epigenetic analyses.Expected value: Our study will be the first to examine the validity of current at-risk criteria as well as of proposed measures to enhance their accuracy (e.g., neuropsychology, genetics) in CAD and to provide starting points for their potential revision. With more and more CAD psychiatrists taking an interest in early detection and intervention in psychosis, the results of the proposed project will be received with immense interest by the international research community. The impact of the proposed study on future early detection research will vary depending on its results: If the sensitivity of ‘fulfilling any current at-risk criterion’ is low, especially in EOP, a completely different or additional set of at-risk criteria for CAD is needed. A more or less comprehensive revision of at-risk criteria for CAD, however, is needed, (i) if the positive predictive power of at-risk criteria is low in AtRisk, (ii) if their specificity and negative predictive power are low in ClinS and GPS and/or (iii) if their prevalence in GPS is high. Such revisions may include the addition of predictors, the elimination of single criteria and/or their redefinition in terms of frequency- and/or time-criteria. Overall, the study’s practical and potential economic impact will be considerable especially in light of the current discussion about the role of at-risk criteria in DSM-5 and the potential for further neurobiological research on this phenotype.