The main objective of the project is to develop and validate molecular diagnostic tools for early detection of Schizophrenia. To this end, we developed three lines of research summarized below.
Elucidating developmental factors related to onset and progression of SZ with a specific emphasis on regulators of neuronal function and synaptic integrity (WP1)
Current status: There is a growing consensus that early detection of SZ, ideally before the onset of serious behavioural, emotional and cognitive dysfunctions, may improve the prognosis for the patients and minimize the societal burden. However, the existing diagnostic approaches rely predominantly on manifest psychiatric symptoms, which may develop only at advanced stages of the underlying pathological process. Improved understanding of SZ neurobiology may result in development of new pre-emptive and preventive therapies substantially delaying or completely eliminating the most severe symptoms of this disorder. With this in mind, we focused on fundamental stages of brain development including its formation, reorganization and maintenance and investigated the most promising leads poised to deliver critical insights into SZ mechanisms.
Understanding the role of immune system in SZ (WP2)
Current status: A promising but currently underexplored approach to early diagnosis of SZ involves developing tests based on blood biomarkers. Mounting evidence suggests that immune and inflammatory responses, both at pre- and postnatal stages, may reflect increased exposure and/or sensitivity to psychosocial stress or anatomical changes in the brain areas in clinically high-risk (CHR) individuals that progress to psychosis. This raises the possibility that relevant molecules released to blood have considerable diagnostic value and that the risk of transition may be associated with specific molecular signatures in blood that involves immune-inflammatory biomarkers. In this WP, we evaluated a panel of metabolic and immune blood-born biochemical markers to identify FEP at-risk subjects. Importantly, several common features shared between SZ and other neuropsychiatric and neurological disorders accompanied by psychosis that were observed will likely expand the overall clinical utility of this WP.
Validating molecular diagnostics for early detection of SZ (WP3)
Current status: The ultimate goal of the proposed project is to develop innovative approaches to early diagnosis of SZ and related conditions through systematic evaluation of biomarkers delivered by WP3. It is imperative to accurately predict the risk of onset of SZ in individuals with as few false positives and false negatives as possible. Earlier studies indicate that it might be difficult to deliver sufficiently reliable, specific and general diagnostics using a single biomarker. Correspondingly, multi-modal strategies have been the focus of several ongoing neuroimaging studies. However, findings from such studies have not yet been translated into clinical practice, in part due to the prohibitively expensive nature of the required imaging techniques. To address this limitation, we used blood-biomarker-based approach for development of clinically useful and affordable biomarker candidates with potential to increase the accuracy of current diagnostic predictors.
