Bipolar disorder (BPD) is a complex psychiatric condition with a highly variable course, and treatment outcome. There is a growing need for personalized treatment strategies. However, the interplay between genetic, clinical, and environmental factors complicates the identification of specific genetic variants associated with the disorder. The study aimed to develop a model to predict treatment outcomes in BPD by using polygenic risk scores (PRS) derived from specific genetic clusters (gcPRS) and clinical variables. The study involved 1538 BD (41.39+/-12.66 years, 59.17% females) individuals from the STEP-BD program, analyzing their genomic data alongside clinical variables using a neural network. A molecular pathway analysis (MPA) based on the interaction network of drugs used for treatment provided the genetic data needed for pPRS calculation. A Neural network was built using pPRS as features together with other variables (including Sex, Age, Scores at baseline) to predict improvement after pharmacological treatment. Performance was evaluated through 5-fold cross-validation. Despite the innovative approach, The predictive model based on polygenic risk scores and clinical variables did not show significant accuracy in predicting the improvement of symptoms after treatment in individuals with bipolar disorder. The maximum accuracy achieved by the model was around 42%. The study's results indicate that the predictive model based on gcPRS and clinical variables did not achieve significant accuracy. Factors such as limited sample size, the complexity of BPD, and population heterogeneity may have contributed to this outcome. The findings underscore the challenges of creating personalized treatment strategies for BPD and highlight the need for further research to better understand the genetic and clinical factors influencing treatment responses.

Marco Calabró has completed its PhD “Clinical and Experimental Neuropsychopharmacology and applications in neurorehabilitation” in 2014, from Messina University, Italy. He is now a Healthcare Researcher (CAT. D) at the Laboratory of Neuroimmunology, Experimental Neurology, and Molecular Biology of the IRCCS Centro Neurolesi "Bonino-Pulejo" institute. His research is primarily focused on the genes and molecular mechanisms related to neurodegenerative and psychiatric disorders.