20 Years of Aberrant Salience in Psychosis: What Have We Learned?

The salience hypothesis of psychosis, which links dopamine dysfunction to delusion formation, is critically evaluated against newer evidence. The hypothesis's specific predictions about dopamine dysfunction's neural and behavioral loci in psychosis are found lacking. Advances in tools for measuring and manipulating dopamine circuits inform this critique. Contemporary theories proposing dopamine's role in belief formation, belief updating under uncertainty, and abductive inference are argued to better explain patient behavior and dopamine function. While influential for uniting neurochemistry with clinical phenomenology, the original hypothesis faces challenges, and the authors highlight novel predictions for future research.

Study at a glance

Abstract

" captured the attention of clinicians and cognitive and behavioral neuroscientists. It has become the de facto way of talking about delusion formation in labs and clinics. Here, evidence for this theory is critically evaluated in consideration of evolving data since its publication. A particular focus is placed on its specific predictions regarding the neural and behavioral loci of dopamine dysfunction in psychosis and finds them lacking. This examination is informed by recent advances in the understanding of the function of the dopamine system and its impacts on behavior following the explosion of new tools and probes for precise measurement and manipulation of dopaminergic circuits. Contemporary theories that have developed since Kapur-which suggest a role for dopamine in belief formation, belief updating under uncertainty, and abductive inference to the best explanation for some set of circumstances-are argued to form a more cogent theory that fits better with the work in patients with delusions and hallucinations, how they behave, and what is known about the function of their dopamine system. The original salience hypothesis has been influential as it attempted to unite neurochemical dysfunction with clinical phenomenology through computational cognitive neuroscience, which has led to the development of novel predictions that the authors highlight as future directions for the field.