@article{a39bd49f4908428ea5ec781009304c47,
title = "Positive and negative valence systems in major depression have distinct clinical features, response to antidepressants, and relationships with immunomarkers",
abstract = "Background: Heterogeneity in major depressive disorder (MDD) is well recognized but not well understood. Core depressive features are reward and emotional symptoms, which reflect dysfunctions in the positive valence (PV) and negative valence (NV) systems, respectively. This study assessed whether PV and NV systems (based on selected symptoms) were associated with different clinical features, antidepressant response, and levels of immunomarkers in adults with MDD. Methods: These analyses used data from combining medications to enhance depression outcomes study (N = 665; n = 166 for immunomarkers). PV and NV symptom scores were extracted from the clinician-rated 30-item Inventory of Depressive Symptomatology. Correlational analyses were conducted. Results: PV and NV symptom scores were substantially associated with different clinical features. PV symptoms (impaired motivation, impaired energy, and anhedonia) were independently associated with female gender (p <.001), older age (p =.012), and higher cognitive and physical impairment (p <.001) according to the 7-item Cognitive and Physical Functioning Questionnaire. Conversely, NV symptoms (anxiety and interpersonal sensitivity) were independently associated with younger age (p =.013), more anxious comorbidities (p =.001 for generalized anxiety disorder and p =.002 for social phobia) and other commonly associated noncriterion symptoms (p <.001). Overall, PV symptoms were more responsive to antidepressants than NV symptoms (p <.0001; Cohen's d =.455). A PV symptom score was positively correlated with the concentration of three proinflammatory and one anti-inflammatory factor. In contrast, an NV symptom score was negatively associated with only one proinflammatory immunomarker. Conclusions: PV and NV system functions appear to be reflected in selected clinical symptoms that differentially relate to other clinical features, treatment outcomes, and immunological function.",
keywords = "RDoC, biomarkers, depression, immunomarkers, major depressive disorder, negative valence, positive valence",
author = "Medeiros, {Gustavo C.} and Rush, {A. John} and Manish Jha and Thomas Carmody and Furman, {Jennifer L.} and Czysz, {Andrew H.} and Trombello, {Joseph M.} and Cooper, {Crystal M.} and Trivedi, {Madhukar H.}",
note = "Funding Information: The authors would like to thank Jeremy A. Kee for his editorial and administrative support. They would also like to thank the trial participants and the clinical staff at each clinical site; without them the project would not have been possible. Finally, the authors appreciate the support given by the Jordan Elizabeth Harris Foundation and the Rees-Jones Foundation. The CO-MED trial (NCT00590863) was funded by NIMH (N01 MH-90003), and in part by the Hersh Foundation. Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for this trial at no cost. Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R25MH101078. Funding Information: Dr Augustus J. Rush has received consulting fees from Akili, Brain Resource, Inc., Compass, Inc., Curbstone Consultant LLC., Emmes Corp., Holmusk, Inc., Liva‐Nova, Sunovion, Takeda, and Taj Medical; speaking fees from Liva‐Nova; royalties from Guilford Press and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named coinventor on two patents: U.S. Patent No. 7,795,033: Methods to predict the outcome of treatment with antidepressant medication, inventors: Francis J. McMahon, Gonzalo E. Laje, Husseini K. Manji, Augustus J. Rush, Silvia Paddock, and Alexander F. Wilson and U.S. Patent No. 7,906,283: Methods to identify patients at risk of developing adverse events during treatment with antidepressant medication, inventors: Francis J. McMahon, Gonzalo E. Laje, Husseini K. Manji, A. John Rush, and Silvia Paddock. Dr Manish Jha has received contract research grant from Acadia Pharmaceutical and Janssen Research. Dr Thomas Carmody has received an honorarium from the University of Texas San Antonio. Dr Joseph M. Trombello currently owns stock in Merck and Gilead Sciences and within the past 36 months previously owned stock in Johnson & Johnson. Dr Madhukar H. Trivedi has received research support from NIMH, NIDA, J&J, and Janssen Research and Development LLC; has served as a consultant for Alkermes, Inc., Allergan, Arcadia Pharmaceuticals, Inc., AstraZeneca, Lundbeck, Medscape, MSI Methylation Sciences, Inc., Merck, Otsuka America Pharmaceuticals, Inc., and Takeda Pharmaceuticals, Inc. Drs Gustavo C. Medeiros, Jennifer L. Furman, Andrew H. Czysz, and Crystal M. Cooper declare no conflict of interests. Funding Information: The authors would like to thank Jeremy A. Kee for his editorial and administrative support. They would also like to thank the trial participants and the clinical staff at each clinical site; without them the project would not have been possible. Finally, the authors appreciate the support given by the Jordan Elizabeth Harris Foundation and the Rees‐Jones Foundation. The CO‐MED trial (NCT00590863) was funded by NIMH (N01 MH‐90003), and in part by the Hersh Foundation. Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for this trial at no cost. Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R25MH101078. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals, Inc.",
year = "2020",
month = aug,
day = "1",
doi = "10.1002/da.23006",
language = "English (US)",
volume = "37",
pages = "771--783",
journal = "Depression and anxiety",
issn = "1091-4269",
publisher = "Wiley-Blackwell",
number = "8",
}