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18/01/2023 - General information

Possible biomarker for early psychosis identified

The Integrated Pharmacology and Systems Neurosciences Research Group of the Hospital del Mar Medical Research Institute has just published a study in Neurobiology of Disease, in which it highlights the role of the CDK5 protein as a possible marker of early psychosis. Furthermore, this protein is modulated by cannabis use. This paves the way for possible future treatments based on CDK5 expression.

Higher levels of the CDK5 protein, which plays an important role in neurone regulation, may act as a biomarker of early psychosis, according to a study by researchers from the Integrated Pharmacology and Systems Neurosciences Research Group and the Neuroimaging in Mental Disorders Research Group at the Hospital del Mar Medical Research Institute (IMIM-Hospital del Mar), published in the journal Neurobiology of Disease. Psychosis is a clinical condition that affects mental state, relationships and behaviour and which is characterised by a loss of contact with reality, with altered perception, cognition, behaviour and emotions. Crucially, it should be noted that cannabis use increases the risk of suffering a psychotic episode by a factor of two, making it important to study the impact of this substance on the disease.

In this study, the research team recruited two groups of patients who had suffered a first psychotic episode, one group of cannabis users and one group of non-users. The study confirmed that cannabis smokers who have undergone a psychotic episode show differences in their CDK5 protein expression compared to those who have not used the substance. As pointed out by Dr. Patricia Robledo, coordinator of the study and one of the authors of the paper, "In human cells and the brains of animal models of psychosis, we have found that the CDK5 protein may be a marker of early psychosis and that it is modulated by cannabis."

Research team

Earlier studies by this research group had already pointed to changes in CDK5 protein expression levels in patients with many years of antipsychotic treatment as a function of cannabis use. The results indicated that CDK5 may be a marker of this disease. To avoid any medication-related effects, in this study, the IMIM-Hospital del Mar team analysed CDK5 expression in patients with untreated psychosis.

The research team worked with samples of the patients' olfactory neuroepithelium, an accessible tissue with a direct connection to the brain, making it ideal for studying biomarkers of psychiatric disorders. This allowed them to demonstrate that CDK5 levels were higher in people who had not used cannabis prior to the psychotic episode. In addition, the symptoms were also different between the two groups of patients. These results were validated in brain samples from an animal model of psychosis in mice. The results indicate that levels of this protein may function as an early indicator of psychosis.

The principal investigator of this work, Marta Barrera-Conde, explains that these results show that "The CDK5 protein differentiates between the population of people with psychosis", as those who smoke cannabis have a different biological profile to those who do not. This may make it possible, in the future, to "search for therapeutic targets and adapt treatments more precisely according to the levels of this protein detected in patients".  This study is one of the first to indicate a possible marker for this pathology, as it has always been difficult to separate the effect of cannabis on patients and its interaction with pharmacological treatment. The findings are relevant because the evidence suggests that the earlier people with psychosis are detected, assessed and treated, the better their prognosis.

Reference article

Barrera-Conde M, Veza-Estévez E, Gomis-Gonzalez M, Garcia-Quintana J, Trabsa A, Martínez-Sadurní L, Pujades M, Perez V, de la Torre R, Bergé D, Robledo P. Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids. Neurobiol Dis. 2022 Dec 5;176:105942. doi: 10.1016/j.nbd.2022.105942. Epub ahead of print. PMID: 36473591.

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