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In the early stages of both mental illnesses, patients often show certain levels of inflammation in the blood as well as changes in the grey matter of the brain. A better understanding of these biomarkers opens up new diagnostic options and therapeutic measures / Publication in “JAMA Psychiatry”
In the early phases of depression and psychosis, patients often show altered inflammatory markers in the blood and structural changes in the grey matter of the brain. This was demonstrated in the international study entitled “Multivariate Brain-Blood Signatures in Early-Stage Depression and Psychosis”, which was published in the scientific journal JAMA Psychiatry. Although diagnosis continues to be based predominantly on clinical symptoms, these biological markers have long been associated with depressive and psychotic disorders and provide important clues about the underlying disease mechanisms. The current study shows that even in the earliest stages of these diseases, fundamentally different inflammatory and brain signatures can be detected. The result enables early therapeutic intervention and can therefore help reduce the risk of severe progression.
The research team was led by Dr Dr David Popovic at the Max Planck Institute of Psychiatry in Munich, PD Dr Lana Kambeitz-Ilankovic at the Faculty of Medicine and University Hospital Cologne, and Professor Dr Rachel Upthegrove at Oxford University. The study is based on the PRONIA (Personalised Prognostic Tools for Early Psychosis Management) project, which was funded by the European Union with six million euros from 2014 to 2019 and led by Professor Dr Nikolaos Koutsouleris, LMU Munich. The project developed innovative forecasting tools and prediction models that can detect the onset of mental illness with greater accuracy.
As part of the current study, the scientists conducted further investigations between 2013 and 2018 at various locations in Germany, Italy, Switzerland, Finland and the United Kingdom on 678 selected participants from the PRONIA study to examine the role of inflammatory biomarkers and brain structure in the early stages of both illnesses. The study included individuals with a recent history of depression or psychosis, as well as those at high clinical risk of developing psychosis, who had received minimal medication treatment to date. Healthy control subjects were also included.
The researchers analysed inflammatory signatures in the blood and brain. These included different levels of cytokines, proteins that influence the interaction and communication between cells, including in the immune response to inflammation. MRI imaging techniques were used to measure brain signatures in order to determine the volume of grey matter in the brain. A particular focus was placed on limbic brain regions, which are mainly responsible for processing emotions.
Overall, the results of the study demonstrated that patients in the early stages of both illnesses showed a complex but largely consistent pattern of different cytokine levels. Surprisingly, the depression and psychosis signatures showed no similarities even in these earliest stages of the disease, neither in the brain nor in the inflammatory markers. In addition, the researchers only observed evidence of impaired cognitive abilities in the psychosis signature, while no cognitive deficits were observed in the depression signature. Overall, there were clear, massive differences between depression and psychosis without intersections across all the data and analyses collected.
“These signatures open up new approaches for both biologically and psychosocially based early interventions in depression and psychosis. This paves the way for customized therapies, depending on whether the young person is in a depression or psychosis development curve,” says lead author David Popovic.
Lana Kambeitz-Ilankovic adds: “Our findings are not intended to replace the established clinical diagnosis based on symptoms and treatment, which also takes into account the psychosocial situation of patients. However, our findings on the respective biomarkers could enable practitioners to better differentiate between the two illnesses at a very early stage in the future.” This would facilitate customized treatment and could reduce the risk of chronification.
However, further research is needed to find a suitable therapeutic intervention for these patient groups. The research team is currently planning a study using diffusion tensor imaging (DTI) to investigate the inflammation in the brain in more detail and to determine how stable the respective signatures remain over time.
PD Dr Lana Kambeitz-Ilankovic
Psychological Director of the Early Recognition and Intervention Centre for Mental Crises (FETZ), Cologne University Hospital
lana.kambeitz-ilankovic@uk-koeln.de
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2842841
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