The effects of acute tryptophan depletion on instrumental reward learning in anorexia nervosa – an fMRI study

Research output: Contribution to journalResearch articleContributedpeer-review


Background The serotonin (5-HT) hypothesis of anorexia nervosa (AN) posits that individuals predisposed toward or recovered from AN (recAN) have a central nervous hyperserotonergic state and therefore restrict food intake as a means to reduce 5-HT availability (via diminished tryptophan-derived precursor supply) and alleviate associated negative mood states. Importantly, the 5-HT system has also been generally implicated in reward processing, which has also been shown to be altered in AN. Methods In this double-blind crossover study, 22 individuals recAN and 25 healthy control participants (HC) underwent functional magnetic resonance imaging (fMRI) while performing an established instrumental reward learning paradigm during acute tryptophan depletion (ATD; a dietary intervention that lowers central nervous 5-HT availability) as well as a sham depletion. Results On a behavioral level, the main effects of reward and ATD were evident, but no group differences were found. fMRI analyses revealed a group × ATD × reward level interaction in the ventral anterior insula during reward anticipation as well as in the medial orbitofrontal cortex during reward consumption. Discussion The precise pattern of results is suggestive of a 'normalization' of reward-related neural responses during ATD in recAN compared to HC. Our results lend further evidence to the 5-HT hypothesis of AN. Decreasing central nervous 5-HT synthesis and availability during ATD and possibly also by dieting may be a means to normalize 5-HT availability and associated brain processes.


Original languageEnglish
Number of pages11
JournalPsychological medicine
Publication statusPublished - 28 Mar 2022

External IDs

Scopus 85128326405
unpaywall 10.1017/s0033291721005493
WOS 000773737800001


Research priority areas of TU Dresden

Sustainable Development Goals


  • Anorexia nervosa, acute tryptophan depletion, fMRI, reward, serotonin

Library keywords