Computationally-informed insights into anhedonia and treatment byκ-opioid receptor antagonism

Abstract

Anhedonia, the loss of pleasure, is prevalent and impairing. Parsing its computational basis promises to explain its transdiagnostic character. We argue that one manifestation of anhedonia - reward insensitivity - may be linked to limited memory capacity. Further, the need to economize on limited capacity engenders a perseverative bias towards frequently chosen actions. Anhedonia may also be linked with deviations from optimal perseveration for a given memory capacity, a pattern that causes inefficiency because it results in less reward for the same memory cost. To test these hypotheses, we perform secondary analysis of a randomized controlled trial testing κ-opioid receptor (KOR) antagonism for anhedonia, as well as analyses of three other datasets. We find that anhedonia is associated with deficits in efficiency but not memory, whereas KOR antagonism (which likely elevates tonic dopamine) increases memory and efficiency. KOR antagonism therefore has distinct cognitive effects, only one related to anhedonia.