Daniel Lundqvist

While psychotic disorders such as schizophrenia represent a significant clinical burden for the individual and large costs for the society, not much is known about the underlying causes. The effort to explain psychotic disorders must include an information processing level since subjective experiences and thoughts are fundamentally altered. We have suggested that there is an unstable low-level information processing in psychosis. In order to compensate for such noise, overly strong top-down influence from prefrontal circuits are recruited and may cause psychotic symptoms like delusions. In the present project we test our hypotheses using a multi-imaging approach. We will perform dynamic network analyses, i.e. connectomics, in MRI-datasets on psychosis patients, and associated phenotypes, with a focus on alterations in prefrontal circuits. We will relate our results to longitudinal behavioral outcomes and treatment effects as well as genetic risk and synaptic density (measured with PET). The results will probe whether these measurements can be used in future precision medicine for clinical assessment of patients. We will also perform task-based functional imaging studies (fMRI and MEG) of psychosis patients to study belief formation dependent on prefrontal cortex, and test causality of these circuits with brain stimulation in non-patients. The project also supports core costs of several ongoing clinical projects such as Karolinska Schizophrenia Project (KaSP).

Background: The age standardised rate of yearly new cancer cases is 190/100 000 globally, by WHO. 30-40% of these will develop depression. There is currently no specific antidepressant treatment regime implemented in the cancer population. This is in spite of the specific needs given by concurrent cancer treatments, limited quality of life from the cancer per se and the often limited life expectancy from a cancer disease. A single dose of psilocybin combined with 3 hours of psychological support has shown rapid (within days) and long term (months or years) antidepressant effect in several small studies in different cancer populations. Large, well designed RCTs are still lacking, as is response predictors for treatment guidance. I am PI of the first RCT of psilocybin treament of depression in Sweden, expected to end randomisation in june 2022. CAPSI: 100 patients with cancer and depression will be randomised to psilocybin or active placebo (2:1) at 4 different regions in Sweden during 2024-2025. Primary end point is depressive symptoms 6 weeks post dose and follw up is 6 months. All subjects will undergo EEG and blood sampling, a subsample (n=50) will also undergo MEG and fMRI, and 25 of them also PET, in order to develop a EEG proxy response signature. Together with markers in blood we will develop a predictor model for psilocybin treatment response. All data will be used to motivate a phase three study with the same PICO and further development of the response markers.

Purpose and goal: Through the program for a digital Europe (DIGITAL), the European Commission wants to increase the efficiency, resilience and sustainability of the EU´s healthcare system, and reduce inequalities in healthcare within the EU. AI and robotics are considered critical areas that need to be developed to reach this objective. TEF HEALTH call is part of the European Strategy for Artificial Intelligence (AI) which aims to optimize the development of AI and promote trust in and use of AI-based software and hardware solutions. Expected results and effects: By making available and combining unique infrastructures for exhaustive in vivo imaging, multimodal ex vivo profiling, and safe and AI-based combinations of these, the Swedish node (CIR, SciLifeLab and RISE) offers internationally competitive opportunities to help European SMEs identify, develop, support and accelerate new and improved precision health applications based on AI-based hardware and software solutions. TEF-Health-konsortiet is expected to serve 500 TEF users by the end of the project and test a total of 5,000 solutions. Approach and implementation: TEF-health begins January 2023. Within the Swedish node, we will organize and make available: IN-VIVO imaging and EX-VIVO OMICS infrastructure, includaing platform access & expert support. A full-service AI development platform, a DATA HUB including retrospectively collected data, a PRECISION DATA HUB including prospectively collected data, and an AI BUSINESS development lab. Sweden contributes to all WPs, and leads WP9 Use cases and demonstrators, where we make Societal challenges, TEF applications, and SME solutions inventories

Use cases database and Demonstrator cases