KaSP - our research
We have designed a collaborative research project between key research groups and clinical partners that will allow a unique Swedish concerted action for psychotic disorders, building platforms for research that will last for many years.
Clinical Platform
The clinical data collection is coordinated by Centre for Psychiatry Research, an organisation joining psychiatric healthcare and researchers.
Patients with first-episode psychosis are currently recruited from four different clinics in Stockholm (Psykiatri Nordväst , Norra Stockholms Psykiatri, Södra Stockholms Psykiatri and Praktikertjänst).
Most patients are naïve to antipsychotic drugs at the time of investigation, made possible by the close interaction between clinical staff and researchers and that many of the examinations are part of the clinical work-up. At present, approximately 100 first-episode drug-naïve patients and about 60 healthy volunteers are enrolled in the program.
All individuals undergo a lumbar puncture for cerebrospinal fluid (CSF) collection, blood sampling, multimodal magnetic resonance imaging (MRI), genetic analysis and extensive clinical characterization including assessment of cognitive function. In subsets of patients, positron emission tomography (PET) is used to examine markers of immune function and neurotransmission.
The KaSP also draws on specific strengths in methodology and expertise present at the Karolinska Institute. For instance, the PET and MRI systems for human and animal imaging at Karolinska Institutet are currently world-leading in performance and image resolution. This unique combination of clinical and research competencies will allow KaSP to address the methodological drawbacks of previous studies on patients with schizophrenia, such as patients often being medicated with antipsychotic drugs, the lack of a healthy control group, lack of CSF analysis, analysis of a restricted number of immune markers, or the use of assays with poor sensitivity and/or specificity.
Experimental Platform
Biochemical or genetic aberrations detected in patients with schizophrenia in the clinical platform form the basis for novel animal models of the disease. Thus, in experimental animals we elicit immune responses, for instance by administration of specific cytokines.
Deviations in genetics (GWAS and Whole Genome Sequencing) found in the patients are functionally investigated by treating rodents with specific pharmacological inhibitors or, when appropriate, by utilizing knock-out (KO) mice with desired targeted deletions. Also, cell cultures utilizing human astrocytes are frequently used to study a role of various cytokines in controlling schizophrenia-relevant metabolici pathways.
This translational approach is designed to systematically and rationally clarify the pathogenic role of genetic and/or distinct biochemical aberrations in schizophrenia. The new animal models are investigated in behavioral settings and with regard to neurotransmission to gain new knowledge of pathophysiological mechanisms. Those models found to have face-, construct- and predictive validity are used to test novel treatments.
By using cellular reprogramming we also create subject-specific cellular models including neurons and glia-like cells derived from diseased subjects and matched healthy controls. These models are then amenable for genetic engineering as well as compound screening.
Results from studies in animals, e.g. identification of signaling pathways including potential pharmacological targets, can be translated back to the clinic and new diagnostic tools that can be used for patient stratification and treatment monitoring.
Our project may not only lead to new therapeutic approaches but will also spark new methodologies aiding diagnoses and the development of biomarkers to monitor efficacy in clinical trials.
Our Visions
- To decipher the pathophysiology of schizophrenia
- To develop biomarkes for a correct diagnosis and to tailor therapymfor individual patients
- To develop novel strategies for schizophrenia treatment