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
Research background

Age and sex are crucial aspects in neurodevelopment and are partly interrelated, presenting as important factors in mental disorders related to neurodevelopment. One example of these disorders are psychotic disorders whose age-at-onset and type (affective vs non-affective) are influenced by sex. Furthermore, in community samples, clinical high risk (CHR) symptoms and criteria that are currently used for an early detection of psychosis, i.e., attenuated and transient psychotic as well as cognitive and perceptual basic symptoms, were reported to be more frequent and less clinically relevant in children and adolescents in whom CHR criteria are also related to lower rates of conversion to psychosis.

Research motivation

From the differences in these age thresholds, i.e., around age 16 for attenuated psychotic symptoms, and around age 18 and 23 for perceptual and cognitive basic symptoms, it was speculated that sex differences in brain and cognitive maturation might lead to lower age thresholds in the clinical significance of BS and possibly APS in females compared to males. Yet, studies on the interaction of age and sex on CHR symptoms and criteria are lacking.

Research objectives

The main objective was to examine the association of age and sex on the presentation and clinical relevance of clinical high-risk criteria and their constituting symptoms in a large community study of 8- to 40-year-olds.

Research methods

We investigated the effect of both age and sex on the prevalence of CHR criteria and symptoms and on their association with psychosocial impairment and mental disorder in a community sample of n = 2916 8- to 40-year-olds. The sample was composed of community participants in two studies: The “Bern Epidemiology At-Risk” (BEAR) study and the “Binational Evaluation of At-Risk Symptoms in Children and Adolescents” (BEARS-Kid) study. Both studies used a stratified sampling method to obtain a representative sample of 7370 people aged 16–40 years in the BEAR study (response rate: 63.4%) and of 980 minors aged 8-17 years in the BEARS-Kid study (response rate: 32.6%) from citizens of the Swiss Canton of Bern.

Research results

Five hundred forty-two (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. Fewer participants met any one of the four symptomatic CHR criteria (n = 82, 2.8%). Both age and sex were significantly 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, i.e., around age 18; they were highest for cognitive basic symptoms and CHR criteria, i.e., around age 23. With the exception of the infrequent attenuated psychotic symptom “speech disorganization”, 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. Only once, in case of functional impairment, an interaction of both age and sex with CHR symptoms – perceptual basic symptoms – became significant.

Research conclusions

Next to confirming the important role of age and sex in the prevalence and clinical relevance of CHR symptoms and criteria, their differential relations to CHR symptoms reveal important insight in possible causal pathways.

Research perspectives

In psychosis research, future efforts at unravelling causal pathways of psychosis, at biomarker discovery and at early therapeutic intervention should consider effects of both sex and age.