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Distinct profiles of anhedonia and reward processing and their prospective associations with quality of life among individuals with mood disorders

Molecular Psychiatry volume 28, pages 5272–5281 (2023)Cite this article

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Abstract

Leading professional health bodies have called for the wider adoption of Patient Reported Outcome Measures, such as quality of life, in research and clinical practice as a means for understanding why the global burden of depression continues to climb despite increased rates of treatment use. Here, we examined whether anhedonia—an often recalcitrant and impairing symptom of depression—along with its neural correlates, was associated with longitudinal changes in patient-reported quality of life among individuals seeking treatment for mood disorders. We recruited 112 participants, including n = 80 individuals with mood disorders (58 unipolar, 22 bipolar) and n = 32 healthy controls (63.4% female). We assessed anhedonia severity along with two electroencephalographic markers of neural reward responsiveness (scalp-level ‘Reward Positivity’ amplitude and source-localized reward-related activation in the dorsal anterior cingulate cortex), and assessed quality of life at baseline, 3- and 6-month follow-up. Anhedonia emerged as a robust correlate of quality of life cross-sectionally and longitudinally among individuals with mood disorders. Furthermore, increased neural reward responsiveness at baseline was associated with greater improvements in quality of life over time, and this improvement was mediated by longitudinal improvements in anhedonia severity. Finally, differences in quality of life observed between individuals with unipolar and bipolar mood disorders were mediated by differences in anhedonia severity. Our findings indicate that anhedonia and its reward-related neural correlates are linked to variability in quality of life over time in individuals with mood disorders. Treatments capable of improving anhedonia and normalizing brain reward function may be necessary for improving broader health outcomes for individuals seeking treatment for depression.

ClinicalTrials.gov identifier: NCT01976975

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Fig. 1: RewP waveform and source localization.
Fig. 2: Associations between anhedonia, reward-related neural markers, and quality of life.
Fig. 3: Schematic showing the potential pathways via which brain reward function may be linked to patient’s overall quality of life.

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Acknowledgements

We would like to acknowledge Thilo Deckersbach, Andrew Nierenberg, and Amy Farabaugh for facilitating recruitment of participants through the Depression Clinic and Research Program and the Bipolar Clinic and Research Program at Massachusetts General Hospital, as well as Daniel Ju Hyung Kim, Emily E. Bernstein, and Margaret E. Gigler for their assistance with patient screening and data collection at these two clinics. We would also like to thank Madeline M. Alexander, Laurie A. Scott, Nancy Hall-Brooks, and David J. Crowley for their important contributions to the screening and clinical assessment of participants recruited through the McLean Hospital Center for Depression, Anxiety and Stress Research.

Funding

Funding

This work was funded by R01MH101521 and R37MH068376 (to DAP). AEW was supported by an Investigator Grant from the National Health and Medical Research Council of Australia (GNT2017521).

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Authors and Affiliations

  1. Black Dog Institute, University of New South Wales, Sydney, NSW, Australia

    Alexis E. Whitton

  2. McLean Hospital & Harvard Medical School, Belmont, MA, USA

    Alexis E. Whitton, Poornima Kumar, Ashleigh V. Rutherford, Manon L. Ironside, Garrett Fitzmaurice, Fei Du & Diego A. Pizzagalli

  3. Emory University, Atlanta, GA, USA

    Michael T. Treadway

  4. Purdue University, West Lafayette, IN, USA

    Dan Foti

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Contributions

DAP, AEW and MTT contributed to the study conception and design; AEW, AVR, and MLI contributed to acquisition of the data; AEW, PK, DF and FD contributed to data analyses; AEW, GF and DAP contributed to statistical analyses and were responsible for data interpretation. AEW drafted the manuscript, and all authors critically reviewed the manuscript and made important intellectual contributions. DAP secured funding and provided overall supervision for the project.

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Correspondence to Diego A. Pizzagalli.

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Competing interests

Over the past 3 years, DAP has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sage Therapeutics, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society and American Psychological Association (for editorial work) and Alkermes; he has received research funding from the Bird Foundation, Brain and Behavior Research Foundation, Dana Foundation, Millennium Pharmaceuticals, National Institute of Mental Health (NIMH), and Wellcome Leap (Multi-Channel Psych); he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. DAP has a financial interest in Neumora Therapeutics (former BlackThorn Therapeutics), which has licensed the copyright to the Probabilistic Reward Task through Harvard University. DAP’s interests were reviewed and are managed by McLean Hospital and Massachusetts General Brigham in accordance with their conflict-of-interest policies. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. In the past 3 years, Michael Treadway has served as a paid consultant for Neumora Therapeutics (formerly BlackThorn Therapeutics) and Boehringer Ingelheim. All other authors report no financial relationships with commercial interest.

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Whitton, A.E., Kumar, P., Treadway, M.T. et al. Distinct profiles of anhedonia and reward processing and their prospective associations with quality of life among individuals with mood disorders. Mol Psychiatry 28, 5272–5281 (2023). https://doi.org/10.1038/s41380-023-02165-1

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