On the relationships between apathy, depression and anhedonia

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Abstract
Background: Apathy, depression and anhedonia are clinically overlapping constructs, which hinders diagnostic clarity and treatment development. This study aimed to comprehensively characterise these syndromes to identify a core set of non-redundant symptoms that maximally dissociate them and to investigate the psychological nature of key distinguishing features. Methods: Data from seven datasets (N=4578) of healthy individuals and patients with major depressive disorder were analysed using the Apathy Motivation Index, Beck Depression Inventory and Snaith-Hamilton Pleasure Scale. A machine-learning algorithm identified the most informative, non-redundant items for dissociating ‘pure’ apathy, depression and anhedonia. The nature of emotional apathy was further investigated with follow-up studies. Results: Although substantial symptom overlap existed, ‘pure’ syndromes were present. Factor analysis revealed a robust five-factor structure, separating depression, anhedonia and three distinct apathy domains (behavioural, social and emotional). Machine learning identified 10 core symptoms that differentiated the pure syndromes with high accuracy (area under the curve >0.90) and could also identify well the presence of each syndrome in individuals suffering from two or more syndromes. Emotional apathy negatively correlated with depression and was specifically associated with reduced affective empathy and a diminished sensitivity to the intensity of negative facial emotions, rather than with alexithymia or antidepressant-induced emotional blunting. Conclusions: Apathy, depression and anhedonia are dissociable constructs with distinct symptom signatures. Emotional apathy is a unique dimension which provides a novel target for research. A 10-item Apathy-Depression-Anhedonia Measure developed here provides a pragmatic tool for rapid, precise phenotyping to guide more personalised therapeutic strategies.
Funding Information
  • NIHR Oxford Biomedical Research Centre (N/A)
  • Wellcome Trust (223264/Z/21/Z)
  • Wellcome Trust (226645/Z/22/Z)
  • NIHR Oxford Health Biomedical Research Centre (N/A)
  • Anhui Provincial Natural Science Foundation (2408085Y047)
  • Jacobs Foundation Research Fellowship (GA 101087700 / Je-S EP/Y014561/1)
  • Jacobs Foundation Research Fellowship (PLP-2021-196)
  • European Research Council (101162047)
  • Medical Research Council (MR/P00878/X)
  • UKRI (EP/X020215/1)
  • Anhui Province Clinical Key Specialty Construction (N/A)
  • Anhui Province Clinical Medical Research Transformation Special Project (202204295107020005)
  • Anhui Province Clinical Medical Research Transformation Special Project (202204295107020006)
  • Anhui Province Translational Medicine Research Institute Project (2023zhyx-C76)

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