Using Intermediate Cognitive Endpoints to Facilitate Translational Research in Psychosis.

Recent advances in the understanding of psychosis have uncovered potential for a paradigm shift in related drug discovery efforts. The study of psychosis is evolving from its origins in serendipity and empiricism to more formal, hypothesis driven accounts of the cognitive substrates underlying hallucinations and delusions. Recent evidence suggests that misattribution of salience and abnormal prediction error might underlie some forms of psychosis. If substantiated, such intermediate constructs could significantly facilitate translational research for drug discovery. Aberrant salience and prediction error can be assayed with simple tests of associative learning in both species, and a convincing back translation of effects, when combined with measures of neurotransmitter release and brain activity could for the first time allow robust, causal connections to be made between molecular mechanisms in rodents and symptoms in patients.