Defining the long-term outcome of psychotic disorders: Calculating risk.

It is difficult to predict the course and outcome of psychotic disorder on the individual level. Some experience a very good treatment response with a rapid and full recovery, while others experience relapses or continuous symptoms and poor function. More precise knowledge about these differences is necessary for better treatment planning and to increase our knowledge about the causes of different illness trajectories. In this project, we have conducted a personal follow-up of the study participants treated for a psychotic disorder (schizophrenia or bipolar disorder) for the first time 10 years ago. During this treatment contact, they were recruited as participants in the research project "Thematically organized psychosis research" (TOP project). They were comprehensively assessed at baseline and also gave their consent to a follow-up. Most were followed up after one year, and we are now planning to find out how they fare in the long term. We are particularly interested in early characteristics indicative of long-term outcomes. We have completed a personal follow-up with participants, to get to know their current situations and have also asked for information from Norwegian patient registers. This will give comprehensive knowledge concerning the long-term course of psychotic disorders which will serve as a basis for several research projects. We have by the end of the follow-up interviewed 320 previous participants (210 with previous treatment for a psychotic disorder and 110 healthy controls) and interviewed 70 participants 20 years after their first treatment (TIPS project). We are currently working to identify specific illness trajectories and associated clinical markers and biomarkers as a first step towards developing a "risk calculator" for different courses of psychotic disorders.

Psychotic disorders are associated with personal distress, societal costs and reductions in life expectancy. Recent research has given clues to the aetiology of the disorders. As much as 80% of first-episode patients experience full symptom remission and the long-term costs are thus primarily related to relapses and residual symptoms. There is despite this is a lack of long-term outcome studies. In the current proposal we combine first-clinical longitudinal studies and genetics studies in the context of Norways health registries. The main hypotheses is that: 1) The development of psychotic disorders is best defined by symptom trajectories rather than by cross-sectional outcomes, 2) The different stages of psychotic disorder involves different pathophysiologies and is best studied in longitudinal studies of early phase patients. The specific focus of the application, is to conduct a 10 year follow-up of first-episode patients recruited in the TOP study 371 with schizophrenia and 94 with bipolar disorders, in addition to 500 healthy controls. All have given consent to be contacted. For these participants we have cognitive- and imaging data, information about environmental risk factors and a comprehensive genetic characterization at baseline, including polygenic risk scores (PGRS) as an estimate of cumulative genetic risk, gene expression and epigenetic data and structural and functional imaging data at baseline. The follow-up will include repeated measures of clinical symptoms,cognitive function and social adjustment plus re-scans. We will also have register information about treatment. The clinical data will be used to identify trajectories and these outcome data will be linked to the comprehensive baseline dataset for prediction purposes. The data on patients from the TIPS study will be used as training set for the trajectories. The findings will ble used to develop a risk calculator, which will be implemented in a new series of longitudinal studies.