Using latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study.

Background: Growing evidence indicates that anhedonia is a multifaceted construct. This study examined the possibility of identifying subgroups of people with anhedonia using multiple reward-related measures to provide greater understanding the Research Domain Criteria's Positive Valence Systems Domain and pathways for developing treatments.
Methods: Latent profile analysis of baseline data from a study that examined the effects of a novel kappa opioid receptor (KOR) antagonist drug on measures and biomarkers associated with anhedonia was used to identify subgroups. Measures included ventral striatal activation during the Monetary Incentive Delay task, response bias in the Probabilistic Reward Task, reward valuation scores from the Effort-Expenditure for Rewards Task, and scores from reward-related self-report measures.
Results: Two subgroups were identified, which differed on self-report measures of reward. Participants in the subgroup reporting more anhedonia also reported more depression and had greater illness severity and functional impairments. Graphs of change with treatment showed a trend for the less severe subgroup to demonstrate higher response to KOR antagonist treatment on the neuroimaging measure, probabilistic reward task, and ratings of functioning; the subgroup with greater severity showed a trend for higher treatment response on reward-related self-report measures.
Limitations: The main limitations include the small sample size and exploratory nature of analyses.
Conclusions: Evidence of possible dissociation between self-reported measures of anhedonia and other measures with respect to treatment response emerged. These results highlight the importance for future research to consider severity of self-reported reward-related deficits and how the relationship across measurement methods may vary with severity.
Competing Interests: Declaration of competing interest Darrow: reports no financial relationship with commercial interests. Pizzagalli: Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society and American Psychological Association (for editorial work) and from Alkermes; he has received research funding from the Brain and Behavior Research Foundation, Dana Foundation, Wellcome Leap, Millennium Pharmaceuticals, and NIMH; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software; he has a financial interest in Neumora Therapeutics, which has licensed the copyright to the human version of the probabilistic reward task through Harvard University. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. Smoski: reports no financial relationships with commercial interests. Mathew: Dr. Mathew has been a consultant for Allergan, Alkermes, Axsome Therapeutics, BioXcel Therapeutics, Clexio Biosciences, Eleusis, EMA Wellness, Engrail Therapeutics, Intra-Cellular Therapies, Greenwich Biosciences, Janssen, Levo Therapeutics, Neurocrine, Perception Neuroscience, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Signant Health and Seelos Therapeutics, and received research support from Biohaven, Janssen, Merck, NIH, NeuroRx, PCORI, Sage Therapeutics, VA, and VistaGen Therapeutics, drug from Biohaven for NIMH-funded study, and support from the Michael E. Debakey VA Medical Center (Houston, TX) for use of resources and facilities and The Menninger Clinic, Houston, Texas. Nurnberger: J.N. has received research funding from Janssen and Assurex. Lisanby: S.H.L. is a co-inventor on a patent for TMS Technology, unrelated to this manuscript. S.H.L. contributed to this article while at Duke University, before joining the National Institute of Mental Health. The views expressed are her own and do not necessarily represent the views of the National Institutes of Health, the Department of Health, or the US government. Iosifescu: In the past 5 years, Dr. Iosifescu has received consulting fees from Alkermes, Axsome, Allergan, Biogen, the Centers for Psychiatric Excellence, Global Medical Education, MyndAnalytics (CNS Response), Jazz, Lundbeck, Otsuka, Precision Neuroscience, Sage, Sunovion; and he has received research grant support (through his academic institutions) from Alkermes, AstraZeneca, Brainsway, LiteCure, NeoSync, Roche, and Shire. Murrough: In the past 5 years, Dr. Murrough has served as a consultant to Allergan, Boehreinger Ingelheim, Clexio Biosciences, Global Medical Education (GME), Otsuka, Sage Therapeutics, and Engrail Therapeutics. Dr. Murrough is named on a patent pending for neuropeptide Y as a treatment for mood and anxiety disorders and on a patent pending for the use of KCNQ channel openers to treat depression and related conditions. The Icahn School of Medicine (employer of Dr. Murrough) is named on a patent and has entered into a licensing agreement and will receive payments related to the use of ketamine or esketamine for the treatment of depression. The Icahn School of Medicine is also named on a patent related to the use of ketamine for the treatment of PTSD. Dr. Murrough is not named on these patents and will not receive any payments. Yang: reports no financial relationship with commercial interests. Weiner: reports no financial relationship with commercial interests. Sanacora: has consulted for Allergan, Alkermes, AstraZeneca, Avanier Pharmaceuticals, Axsome Therapeutics, Biogen, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Clexio Biosciences, Denovo Biopharma, EMA- Wellness, Engrail, Freedom, Gilgamesh, Hoffman La-Roche, Intra-Cellular Therapies, Janssen, Levo, Lundbeck, Merck, Naurex, Navitor Pharmaceuticals, Neurocrine Biosciences, Novartis, Noven Pharmaceuticals, Otsuka, Praxis Therapeutics, Perception Neuroscience, Praxis Therapeutics, Sage Pharmaceuticals, Seelos Pharmaceuticals, Taisho Pharmaceuticals, Teva, Valeant, Vistagen Therapeutics, and XW Labs. GS also received research funding from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Hoffman La-Roche, Merck, Naurex, Servier and Usona Institute. G.S. holds equity in BioHaven Pharmaceuticals and is a co-inventor on a US patent (#8,778,979) held by Yale University and a co-inventor on US Provisional Patent Application No. 047162-7177P1 (00754) filed on August 20, 2018, by Yale University Office of Cooperative Research. Yale University (Employer of Dr. Sanacora) has a financial relationship with Janssen Pharmaceuticals and may in the future receive financial benefits from this relationship. Keefe: During the period that work was conducted on this study, R.S.E.K. was the owner of VeraSci, a for-profit company that provides clinical trial support and other services for over 100 pharmaceutical companies and other institutions. Song: has received research support from the NIH and GE Healthcare. Goodman: W.G. has consulted for Biohaven Pharmaceuticals, received research funding from the NIH, the McNair Foundation, and Biohaven Pharmaceuticals, and received donated devices from Medtronic. Whitton: Dr. Whitton was partially supported by a grant from the National Health and Medical Research Council of Australia (GNT: 1110773). Potter: Is on a DSMB for Agene-Bio and Regenacy, has stock ownership in Merck, and has received consulting fees from Karuna, Eliem, Neurocrine, Emerald Lake Safety, Boston Pharmaceuticals, and Otsuka and receives research funding from the NIH as a co-PI on a small business grant to praxis Bioresearch. Krystal: Dr. Krystal has received research grants from Janssen Pharmaceuticals, Axsome Pharmaceutics, Reveal Biosensors, The Ray and Dagmar Dolby Family Fund, and the National Institutes of Health. He has received consulting fees from Adare, Axsome Therapeutics, Big Health, Eisai, Evecxia, Ferring Pharmaceuticals, Galderma, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, Takeda, and Angelini. He owns options of Big Health.
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