About the project
Youth-TOP is a scientific study aimed at increasing our understanding of young people who develop psychosis. Psychosis during adolescence can have major consequences for health, development, and everyday functioning, yet we still know relatively little about why it develops and how it progresses over time.
The study aims to improve our understanding of causes and risk factors and, in the longer term, to contribute to more accurate diagnosis, better treatment, and potentially preventive interventions. We investigate clinical symptoms, cognitive functioning, and genetic and other biological risk markers. Participants also undergo brain imaging using magnetic resonance imaging (MRI).
Background
Both genetic and environmental factors can influence the risk of psychosis, but the interplay between these factors is still not sufficiently understood. In particular, relatively little is known about the biological mechanisms involved in psychosis that develops during adolescence.
In Youth-TOP, we investigate associations between environmental and biological risk factors, clinical characteristics, and brain structure and function. Participants are followed over time, allowing us to study factors including the course of illness, cognition, medication use, genetic factors, immune and infection markers, and previous birth complications. We also conduct structural and functional brain imaging.
Our aim is to identify clinical and biological markers that can help us understand how the illness develops, assess risk and prognosis, and, in the longer term, improve diagnosis and treatment. To date, the study has resulted in 22 scientific publications, with several more in progress.
Participants
So far, we have included approximately 90 adolescents with psychotic disorders, including schizophrenia and bipolar disorder, or with suspected psychotic disorders. In addition, around 130 adolescents without psychotic disorders from Oslo and the surrounding area participate as healthy controls.
We are continuing to recruit new participants, and the project has approval from the Regional Committees for Medical and Health Research Ethics (REK) to continue recruitment until the end of 2033. Participation in the study is voluntary, and all participants may withdraw from the study at any time by contacting us.
Since October 2024, new participants in Youth-TOP have also been given the opportunity to participate in the TOP Research Registry and Biobank. Consent to participate allows health data and biological samples to be used in several research projects on severe mental disorders.
More information is available on the “TOP Research Registry and Biobank" (in Norwegian) webpage at Oslo University Hospital.
Collaboration
Youth-TOP is a collaboration between the University of Oslo, Oslo University Hospital, Diakonhjemmet Hospital, and Østfold Hospital Trust, and forms part of the TOP Study. The study is funded by the Research Council of Norway (RCN) and the South-Eastern Norway Regional Health Authority. The project also collaborates closely with Karolinska Institutet in Stockholm.
Because early-onset psychosis is relatively rare, national and international collaboration is essential in order to obtain larger samples and more robust evidence. As part of this work, we have in recent years coordinated the ENIGMA-EOP working group, which is part of the international ENIGMA research network. The group brings together data from multiple research centres to investigate clinical characteristics, genetics, and brain structure and function in young people with early-onset psychosis.
Research findings
Through ENIGMA-EOP, we have so far published four major scientific studies. These studies have identified differences in several subcortical brain structures as well as in the brain’s white and grey matter (Gurholt et al., 2022; Barth et al., 2023; Si et al., 2024). The white-matter differences partly differed from those previously reported in adults with psychotic disorders and were most pronounced in boys with schizophrenia (Barth et al., 2023). We have also found differences in cortical thickness, surface area, volume, and folding. Group differences in cortical surface area were more pronounced than corresponding findings in adults with psychotic disorders (Nerland et al., 2026). This may be consistent with early developmental processes playing a particularly important role in early-onset psychosis.
In other studies, we have investigated cognitive functioning in adolescents with psychotic disorders. To enable the assessment of cognitive abilities in this age group, we first developed age- and sex-adjusted normative data (Smelror et al., 2019). Among adolescents with early-onset psychosis, we found an association between verbal learning and a measure of everyday functioning. The severity of negative and disorganised symptoms also influenced this relationship (Smelror et al., 2020). A subsequent study showed that negative symptoms could be divided into dimensions including apathy and reduced emotional and verbal expression, and that these symptoms were associated with poorer verbal learning at the group level (Mørch-Johnsen et al., 2022).
We have also investigated relationships between the immune system, stress, and psychiatric symptoms in adolescents with psychotic disorders. Our findings suggest, among other things, associations between stress, markers of inflammation, and depressive symptoms (Wedervang-Resell et al., 2020a). In another study, we found differences in blood lipid levels, including among adolescents who had not used antipsychotic medication. Higher triglyceride levels were also associated with more pronounced negative symptoms (Wedervang-Resell et al., 2020b). These findings may contribute to a better understanding of the biological mechanisms involved in psychotic disorders, as well as factors that may affect physical health.
It is important to note that the research findings described above primarily concern differences and associations observed at the group level. These differences are often small, and there is considerable variation between individuals. The findings therefore do not necessarily provide information about any particular individual with or without a psychotic disorder. Nevertheless, even small group-level differences can provide important insights into possible biological mechanisms and contribute to a better understanding of psychotic disorders.
Ongoing research studies
The project Low-grade inflammation: a possible link between childhood trauma and psychosis in adolescence builds on our previous research. In this study, we are investigating whether adverse childhood experiences are associated with low-grade inflammation in adolescents with psychosis. The study is based on previous research suggesting links between such experiences and alterations in the body’s stress and immune systems in severe mental disorders.
In other ongoing studies, we are investigating how the brain develops over time and how this development may be related to early risk factors and antipsychotic treatment. We also compare individuals whose psychosis began during adolescence with those whose psychosis began in adulthood. The aim is to determine whether differences in brain structure and function are particularly associated with early-onset psychosis and to identify factors that may influence the course of illness and prognosis.
Further reading
Agartz, I. & Smelror, R. (2023). Adolescent Psychosis, Clinical and Scientific Perspectives (1st ed.). Elsevier.