Anxiety and anhedonia in depression: Associations with neuroticism and cognitive control
Allen Liao, Robrina Walker, Thomas J Carmody, Crystal Cooper, Meredith A Shaw, Bruce D Grannemann, Phil Adams, Gerard E Bruder, Melvin G McInnis, Christian A Webb, Daniel G Dillon, Diego A Pizzagalli, Mary L Phillips, Benji T Kurian, Maurizio Fava, Ramin V Parsey, Patrick J McGrath, Myrna M Weissman, Madhukar H Trivedi, Allen Liao, Robrina Walker, Thomas J Carmody, Crystal Cooper, Meredith A Shaw, Bruce D Grannemann, Phil Adams, Gerard E Bruder, Melvin G McInnis, Christian A Webb, Daniel G Dillon, Diego A Pizzagalli, Mary L Phillips, Benji T Kurian, Maurizio Fava, Ramin V Parsey, Patrick J McGrath, Myrna M Weissman, Madhukar H Trivedi
Abstract
Background: Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these clinical presentations remain unclear. Neuroticism, impaired cognitive control, and blunted reward learning may be critical processes involved in MDD and may help to explain symptoms of anxiety and anhedonia.
Methods: Using baseline data from patients with early-onset MDD (N = 296) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, we conducted a path analysis to model relationships between neuroticism, cognitive control, and reward learning to levels of anxiety and anhedonia.
Results: Neuroticism was positively associated with both anhedonia (standardized coefficient = 0.26, p < .001) and anxiety (standardized coefficient = 0.40, p < .001). Cognitive control was negatively associated with anxiety (standardized coefficient = -0.18, p < .05). Reward learning was not significantly associated with either anxiety or anhedonia.
Limitations: Extraneous variables not included in the model may have even more influence in explaining symptoms of anxiety and anhedonia. Restricted range in these variables may have attenuated some of the hypothesized relationships. Most important, because this was a cross-sectional analysis in a currently depressed sample, we cannot draw any causal conclusions without experimental and longitudinal data.
Conclusions: These cross-sectional findings suggest that neuroticism may contribute to anxiety and anhedonia in patients with early onset and either chronic or recurrent MDD, while enhanced cognitive control may protect against anxiety.
Trial registration: ClinicalTrials.gov NCT01407094.
Keywords: Anhedonia; Anxiety; Cognitive control; Depression; Neuroticism.
Conflict of interest statement
Conflicts of Interest
Dr. McInnis has in the past 36 months MG McInnis consulted with Janssen Pharmaceuticals and Otsuka Pharmaceuticals. Dr. Pizzagalli has over the last 36 months received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehringer Ingelheim, Pfizer, and Posit Science for activities unrelated to the current research. Dr. Fava has received research support from Abbott Laboratories, Acadia Pharmaceuticals, Alkermes, Inc., American Cyanamid, Aspect Medical Systems, AstraZeneca; Avanir Pharmaceuticals, AXSOME Therapeutics, BioResearch, BrainCells Inc., Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Cerecor, Clintara, LLC, Covance, Covidien, Eli Lilly and Company, EnVivo Pharmaceuticals, Inc., Euthymics Bioscience, Inc., Forest Pharmaceuticals, Inc., FORUM Pharmaceuticals, Ganeden Biotech, Inc., GlaxoSmithKline, Harvard Clinical Research Institute, Hoffman-LaRoche, Icon Clinical Research, i3 Innovus/Ingenix, Janssen R&D, LLC, Jed Foundation, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Lundbeck Inc., Marinus Pharmaceuticals, MedAvante, Methylation Sciences Inc, National Alliance for Research on Schizophrenia & Depression (NARSAD), National Center for Complementary and Alternative Medicine (NCCAM), National Coordinating Center for Integrated Medicine (NiiCM), National Institute of Drug Abuse (NIDA), National Institute of Mental Health (NIMH), Neuralstem, Inc., NeuroRx, Novartis AG, Organon Pharmaceuticals, Otsuka Pharmaceutical Development, Inc., PamLab, LLC., Pfizer Inc., Pharmacia-Upjohn, Pharmaceutical Research Associates., Inc., Pharmavite® LLC, PharmoRx Therapeutics, Photothera, Reckitt Benckiser, Roche Pharmaceuticals, RCT Logic, LLC (formerly Clinical Trials Solutions, LLC), Sanofi-Aventis US LLC, Shire, Solvay Pharmaceuticals, Inc., Stanley Medical Research Institute (SMRI), Synthelabo, Taisho Pharmaceuticals, Takeda Pharmaceuticals, Tal Medical, VistaGen, Wyeth-Ayerst Laboratories. He has also served as advisor or consultant to Abbott Laboratories, Acadia, Affectis Pharmaceuticals AG, Alkermes, Inc., Amarin Pharma Inc., Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Avanir Pharmaceuticals, AXSOME Therapeutics, Bayer AG, Best Practice Project Management, Inc., Biogen, BioMarin Pharmaceuticals, Inc., Biovail Corporation, BrainCells Inc, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Inc., Cerecor, CNS Response, Inc., Compellis Pharmaceuticals, Cypress Pharmaceutical, Inc., DiagnoSearch Life Sciences (P) Ltd., Dinippon Sumitomo Pharma Co. Inc., Dov Pharmaceuticals, Inc., Edgemont Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, EnVivo Pharmaceuticals, Inc., ePharmaSolutions, EPIX Pharmaceuticals, Inc., Euthymics Bioscience, Inc., Fabre-Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, Inc., Forum Pharmaceuticals, GenOmind, LLC, GlaxoSmithKline, Grunenthal GmbH, Indivior, i3 Innovus/Ingenis, Intracellular, Janssen Pharmaceutica, Jazz Pharmaceuticals, Inc., Johnson & Johnson Pharmaceutical Research & Development, LLC, Knoll Pharmaceuticals Corp., Labopharm Inc., Lorex Pharmaceuticals, Lundbeck Inc., Marinus Pharmaceuticals, MedAvante, Inc., Merck & Co., Inc., MSI Methylation Sciences, Inc., Naurex, Inc., Navitor Pharmaceuticals, Inc., Nestle Health Sciences, Neuralstem, Inc., Neuronetics, Inc., NextWave Pharmaceuticals, Novartis AG, Nutrition 21, Orexigen Therapeutics, Inc., Organon Pharmaceuticals, Osmotica, Otsuka Pharmaceuticals, Pamlab, LLC., Pfizer Inc., PharmaStar, Pharmavite® LLC., PharmoRx Therapeutics, Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc., PPD, Purdue Pharma, Puretech Ventures, PsychoGenics, Psylin Neurosciences, Inc., RCT Logic, LLC (formerly Clinical Trials Solutions, LLC), Relmada Therapeutics, Inc., Rexahn Pharmaceuticals, Inc., Ridge Diagnostics, Inc., Roche, Sanofi-Aventis US LLC., Sepracor Inc., Servier Laboratories, Schering-Plough Corporation, Shenox Pharmaceuticals, Solvay Pharmaceuticals, Inc., Somaxon Pharmaceuticals, Inc., Somerset Pharmaceuticals, Inc., Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Inc., Synthelabo, Taisho Pharmaceuticals, Takeda Pharmaceutical Company Limited, Tal Medical, Inc., Tetragenex, Teva Pharmaceuticals, TransForm Pharmaceuticals, Inc., Transcept Pharmaceuticals, Inc., Usona Institute,Inc., Vanda Pharmaceuticals, Inc., Versant Venture Management, LLC, VistaGen; He has received speaking or publishing fees from Adamed, Co, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon, Inc., CME Institute/Physicians Postgraduate Press, Inc., Eli Lilly and Company, Forest Pharmaceuticals, Inc., GlaxoSmithKline, Imedex, LLC, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis AG, Organon Pharmaceuticals, Pfizer Inc., PharmaStar, United BioSource, Corp., Wyeth-Ayerst Laboratories; He has a patent for Sequential Parallel Comparison Design (SPCD), licensed by MGH to Pharmaceutical Product Development, LLC (PPD) (US_7840419, US_7647235, US_7983936, US_8145504, US_8145505), pharmacogenomics of Depression Treatment with Folate (US_9546401, US_9540691), and a patent application for a combination of Ketamine plus Scopolamine in Major Depressive Disorder (MDD), licensed by MGH to Biohaven. Dr. McGrath has received funding from the National Institute of Mental Health, New York State Department of Mental Hygiene, Research Foundation for Mental Hygiene (New York State), Forest Research Laboratories, Sunovion Pharmaceuticals, and Naurex Pharmaceuticals (now Allergan). In the past 36 months, Dr. Trivedi has served as a consultant or on the advisory board for Alkeremes Inc., Akili Interactive, Navitor, Otsuka America Pharmaceutical Inc., Allergan Pharmaceuticals, Brintellix Global, Global Medical Education Inc, Health Research Associates, Lundbeck Research USA, Medscape, MSI Methylation Sciences – Pamlab Inc., One Carbon Therapeutics, Pfizer Inc, Takeda Global Research, Avanir Pharmaceuticals, Forest Pharmaceuticals, Insys, Johnson & Johnson Pharmaceutical Research & Development, Lilly Research Laboratories, Medscape, Merck & Co. Inc, Mitsubishi Pharma, Neuronetics Inc., Pamlab LLC, Ridge Diagnostics, SHIRE Development LLC, Sunovion Pharmaceuticals Inc, Takeda Global Research. He has received grants from the National Institute of Mental Health (NIMH), National Institute of Drug Abuse (NIDA), National Center for Advancing Translational Sciences (NCATS), Cancer Prevention and Research Institute of Texas (CPRIT), the Patient-Centered Outcomes Research Institute (PCORI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Agency for Healthcare Research and Quality (AHRQ), Johnson & Johnson. He has author agreements with Janssen Asia Pacific and Oxford University Press. He has received honoraria from the American Psychiatric Association. And he has received royalties from Janssen Research and Development LLC. Dr. Walker’s research is funded by NIDA, and Alkermes, Inc. donated medication for a NIDA-funded study unrelated to the current manuscript. Dr. Dillon has served in the last three years as a consultant for Pfizer, Inc., for activities unrelated to the current project. In the past three years, Dr. Weissman received funding from the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Sackler Foundation, and the Templeton Foundation; and receives royalties from the Oxford University Press, Perseus Press, the American Psychiatric Association Press, and MultiHealth Systems. Mr. Grannemann, and Drs. Liao, Carmody, Cooper, Bruder, Webb, Shaw, Adams, Kurian, Parsey, and Phillips have no conflicts to report.
Copyright © 2018. Published by Elsevier B.V.
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Source: PubMed