Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. May 19, 2020; 10(5): 101-124
Published online May 19, 2020. doi: 10.5498/wjp.v10.i5.101
Effects of age and sex on clinical high-risk for psychosis in the community
Frauke Schultze-Lutter, Benno G Schimmelmann, Rahel Flückiger, Chantal Michel
Frauke Schultze-Lutter, Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf 40692, Germany
Benno G Schimmelmann, Rahel Flückiger, Chantal Michel, University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern 3000, Switzerland
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 research; Schultze-Lutter F, Flückiger R and Michel C performed the research; Schultze-Lutter F analyzed the data; Schultze-Lutter F wrote the first draft of the paper; Schimmelmann BG, Flückiger R and Michel C critically revised the first draft; all authors agreed to the submitted version.
Supported by the Swiss National Science Foundation, No. 135381 and No. 144100.
Institutional review board statement: The study was reviewed and approved by the ethics committee of the University of Bern, “Kantonale Ethikkommission Bern (KEK)” (Switzerland).
Informed consent statement: All participants of the BEARS-Kid study, or their legal guardian, provided informed written consent prior to study enrolment. In the BEAR study, participation in the telephone interview after written information equalled informed consent.
Conflict-of-interest statement: The authors report no conflicts of interest in relation to the topic of this study. Outside this work, Dr. Schimmelmann received honoraria and is on the speakers board of Takeda (Shire) and Infectopharm.
Data sharing statement: Data of the studies are not publicly available but might be shared upon request from the first author.
STROBE statement: The “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) guidelines were carefully observed throughout the preparation of this manuscript.
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, Head of Early Detection Research Unit, Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Bergische Landstraße 2, Düsseldorf 40629, Germany. frauke.schultze-lutter@lvr.de
Received: December 26, 2019
Peer-review started: December 26, 2019
First decision: February 29, 2020
Revised: March 13, 2020
Accepted: March 30, 2020
Article in press: March 30, 2020
Published online: May 19, 2020

Recent reports of both heightened prevalence rates and limited clinical relevance of clinical high-risk (CHR) criteria and their relevant symptoms in children and adolescents indicate an important role of neurodevelopment in the early detection of psychoses. Furthermore, sex effects in CHR symptoms have been reported, though studies were inconclusive. As sex also impacts on neurodevelopment, we expected that sex might have an additional contribution to age in the prevalence and clinical relevance of CHR symptoms and criteria.


To investigate age and sex effects on CHR criteria and symptoms and their association with psychosocial impairment and mental disorder.


In this cross-sectional cohort study, n = 2916 8- to 40-year-olds, randomly drawn from the population register of the Swiss canton Bern, were assessed in semi-structured interviews by phone or face-to-face for CHR symptoms and criteria using the Structured Interview for Psychosis-Risk Syndromes and the Schizophrenia Proneness Instrument in its child and youth, and adult version, respectively. Furthermore, social and occupational functioning and DSM-IV axis I disorders were assessed. Simple and interaction effects of age and sex on CHR symptoms and criteria, and interaction effects of age, sex, and CHR symptoms and criteria on presentation of functional impairment and of non-psychotic disorder were investigated using logistic regression analyses.


Altogether, 542 (18.6%) participants reported any CHR symptom; of these, 261 (9.0%) participants reported any one of the 11 criteria relevant cognitive and perceptual basic symptoms, and 381 (13.1%) any one of the five attenuated or transient psychotic symptoms (attenuated psychotic symptoms/brief intermittent psychotic symptoms). Fewer participants met any one of the CHR criteria (n = 82, 2.8%) or any one of the three recently recommended CHR criteria (n = 38, 1.3%). Both age and sex were significantly (P < 0.05) associated with CHR symptoms and criteria, mostly by younger age and female sex. Though slightly differing between symptom groups, age thresholds were detected around the turn from adolescence to adulthood; they were highest for cognitive basic symptoms and CHR criteria. With the exception of the infrequent speech disorganization attenuated psychotic symptom, the interaction of age with CHR symptoms and criteria predicted functional impairment; whereas, independent of each other, sex and CHR symptoms mostly predicted mental disorders.


Age and sex differentially impact on CHR symptoms and criteria; these differences may support better understanding of causal pathways. Thus, future CHR studies should consider effects of sex and age.

Keywords: Psychosis, Clinical high-risk, Attenuated psychotic symptoms, Basic symptoms, Community, Age, Sex, Interview assessment, Prevalence

Core tip: Age and sex are crucial aspects in neurodevelopment and are partly interrelated, presenting as important factors in mental disorders related to neurodevelopment, such as psychosis. However, both age- and sex-related aspects are frequently neglected in the early detection of psychosis. Therefore, this highly original study examined the association of age and sex with the presentation and clinical relevance of clinical high-risk criteria and their constituting symptoms in a large community sample of 8- to 40-year-olds. Next to confirming the important role of age and sex, their differential relations to clinical high-risk symptoms reveal important insight in possible causal pathways.