Primary Goals

Bipolar disorder (BD), especially BD type I, is a highly prevalent mental disorder and a is a highly prevalent mental disorder and an important factor for suicide. Lithium is the key treatment for prevention of BD relapse and has a proven suicide prevention effect. Whilst many cases become asymptomatic with lithium treatment, the majority show sub-optimal response. The R-LiNK project is structured in the context of

• the high occurrence and relapse rates of BDI are not only a major burden toward the individual with them, but also a large global and economic cost to society
• the absence of valid predictors of lithium response
• the need for development of personalized medicine in psychiatry
• the identification of biomarkers for predicting individual lithium treatment response can enable the personalization of treatment, define criteria for the stratification of BD cases and further refine the clinical response phenotype

The objectives of this project are to:

• improve outcomes of bipolar I disorder (BDI) cases prescribed lithium through the application of stratified approaches
• optimize the early prediction of lithium response using a set of multi-modal biomarkers (“blood omics”, Magnetic Resonance Imaging and Li7-Magnetic Resonance Spectroscopy derived-markers)
• develop a multidisciplinary multinational network of experts to undertake this and future projects on personalized diagnostics and therapeutics and
• implement new, powerful technologies to characterize brain lithium distribution and the blood molecular signature of lithium in responders and non-responders

This cutting edge approach will identify the eligibility criteria for treatment with lithium in BD in terms of response, safety and tolerability.

Expected impacts include:

• For patients: stabilization of mental state (reduced variability on symptoms and fewer episode relapse, decrease in suicidal behaviors), improved clinical and social functioning and better quality of life. Improved patients’ engagement and autonomy
• For clinicians: introduction of a decision making and a screening tool leading to modifications of clinical guidelines on the selection of BDI cases for lithium treatment and enhancing clinical practice
• For the society: longer-term reduction in cost and global burden of BDI (fewer hospitalizations, lower cost associated with all cause morbidity and mortality)
• For research: opening up of several new avenues such as replication studies to validate the predictors, new hypotheses to further explore the mechanism(s) of action of lithium, complementarity with ongoing research on lithium (pharmacogenetics e.g. ConLiGen and the work of IGSLI)
• For industry through the exploitation of the results: medical devices, diagnostic kits, tools based on the molecular signature in responders to screen new drugs for development

Expected results are also likely to strengthen our understanding of the brain regions as well as the molecular pathways involved in lithium response in BDI. The translational aspects of the programme offer a unique opportunity for early transfer of our laboratory findings to clinical practice. In addition, the research program proposed by the R-LiNK initiative will open up new avenues for research to enable a better understanding of the mechanisms of action of lithium, and a template for examining other putative mood stabilizer drugs.