Using intermediate cognitive endpoints to facilitate translational research in psychosis

- Psychosis is a transdiagnostic complex of symptoms that may be more effectively fractionated.
- Aberrant salience and prediction error may provide intermediate cognitive constructs of psychosis.
- Dopamine and glutamate hypotheses may relate to and explain dysfunction in salience and prediction error processes.
- Translational technologies and endpoints can now be developed to reconcile findings across species.

Recent advances in the understanding of psychosis have uncovered potential for a paradigm shift in related drug discovery. 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 abnormal salience and prediction error might underlie some forms of psychosis. Such intermediate constructs could significantly facilitate translational research. Salience and prediction error can be assayed with simple tests of associative learning, 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.