Research agenda to advance anhedonia assessment, understanding and treatment: an ECNP-GALENOS expert meeting report
B W J H Penninx, Martien J H Kas, Gerard R Dawson, Christoph U Correll, Catherine J Harmer, Derek L Buhl, Michele De Prisco, James Downs, Dennis Hernaus, Seth C Hopkins, Masud Husain, Shaun Johnson, Ruth Mckernan, Edoardo G Ostinelli, Diego A Pizzagalli, Christopher R Pryce, Andreas Reif, Rudy Schreiber, Alessandro Serretti, Spyridon Siafis, Elizabeth Tunbridge, Daniel Umbricht, Christiaan H Vinkers, Andrea CiprianiAnhedonia, broadly defined as a reduced ability to experience interest or pleasure, represents an important transdiagnostic neuropsychiatric symptom dimension which may benefit from targeted diagnostics and treatments. Different lines of research have proposed that it comprises multiple facets, including deficits in anticipatory (‘wanting’) and consummatory (‘liking’) reward processing as well as reward learning and affects different aspects of life (eg, social, physical, cognitive). Certain facets—more specifically anticipation, motivation and reward learning—likely involve blunted phasic dopaminergic signalling. However, recent meta-analytical evidence of human depression studies indicates that prodopaminergic antidepressants produce relatively small improvements in anhedonia symptoms and suggest that mechanisms beyond dopamine likely contribute to anhedonia. This stimulated an expert meeting to review the literature and define priorities for future research in anhedonia. A central key priority is developing a translational biologically-informed nomenclature and consensus that solves the current mismatch between constructs, paradigms and measures, and mechanisms, which separates discrete reward-related processes such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure. Clinical research priorities are improved multimodal measurement tools, integrating neurobiological frameworks (eg, neuroimaging, electrophysiology and liquid biomarkers capturing dopaminergic, glutamatergic, opioid and immunometabolic pathways) and transdiagnostic studies across neuropsychiatric disorders and developmental stages. Innovative trial designs that explicitly target anhedonic phenotypes as a primary outcome and test mechanism-based interventions are also needed. Translational research recommendations include back-translation strategies that begin with patient-relevant phenotypes followed by the development of comparable human and animal tasks that target reward-related processes, such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure, improve cross-species behavioural paradigms and enhance methodological rigour and reproducibility. Collectively, these recommendations will help refine the conceptualisation of anhedonia and advance its role within precision psychiatry as a mechanistically grounded target across multiple disorders.