The largely unknown etiology and pathophysiology of psychiatric disorders has significantly hampered effective drug discovery and development; to wit, nearly all first-generation antipsychotics and mood stabilizers have been discovered under serendipitous circumstances. However, recent advances in genetics and pathological technologies have provided new avenues into investigating and connecting genetic components in the etiology of psychiatric disorders with pathophysiological changes in the patient's brain. With this newfound synergy, we are now able to commence truly innovative drug discovery based on strong scientific rationale.
Our approach is to pinpoint common biological pathways disturbed in both psychiatric patients and genetically-engineered animal models (targeting both individual genes and CNVs discovered in patients) and use these commonalities to generate testable working hypotheses. We have obtained patient datasets via participation in the Lieber Institute for Brain Development's (LIBD) Pharma RNA-Seq Consortium, BrainSEQ^TM, a precompetitive research collaboration aimed at completing RNA sequencing of up to 800 brain samples from DLPFC and hippocampus. This approach facilitates streamlined, comprehensive drug target selection where candidate compounds are evaluated using behavioral testing and pathophysiological measures, with the eventual goal of reversing the disturbed pathways in gene-manipulated animal models and, ultimately, human patients. Our objective is to achieve precision medicine in psychiatry. In doing this, we aim to tackle emerging problems, including disease- and patient-specific biomarkers used for diagnosis and stratification.