Abstract
Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.
Original language | English (US) |
---|---|
Pages (from-to) | 1500-1510 |
Number of pages | 11 |
Journal | Molecular psychiatry |
Volume | 25 |
Issue number | 7 |
DOIs | |
State | Published - Jul 1 2020 |
ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
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Discovery and replication of cerebral blood flow differences in major depressive disorder. / Cooper, Crystal M.; Chin Fatt, Cherise R.; Liu, Peiying; Grannemann, Bruce D.; Carmody, Thomas; Almeida, Jorge R.C.; Deckersbach, Thilo; Fava, Maurizio; Kurian, Benji T.; Malchow, Ashley L.; McGrath, Patrick J.; McInnis, Melvin; Oquendo, Maria A.; Parsey, Ramin V.; Bartlett, Elizabeth; Weissman, Myrna; Phillips, Mary L.; Lu, Hanzhang; Trivedi, Madhukar H.
In: Molecular psychiatry, Vol. 25, No. 7, 01.07.2020, p. 1500-1510.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Discovery and replication of cerebral blood flow differences in major depressive disorder
AU - Cooper, Crystal M.
AU - Chin Fatt, Cherise R.
AU - Liu, Peiying
AU - Grannemann, Bruce D.
AU - Carmody, Thomas
AU - Almeida, Jorge R.C.
AU - Deckersbach, Thilo
AU - Fava, Maurizio
AU - Kurian, Benji T.
AU - Malchow, Ashley L.
AU - McGrath, Patrick J.
AU - McInnis, Melvin
AU - Oquendo, Maria A.
AU - Parsey, Ramin V.
AU - Bartlett, Elizabeth
AU - Weissman, Myrna
AU - Phillips, Mary L.
AU - Lu, Hanzhang
AU - Trivedi, Madhukar H.
N1 - Funding Information: Acknowledgements The EMBARC study reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers U01MH092221 (Trivedi MH PI) and U01MH092250 (Weissman MM PI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center and Data Center at Columbia University. Thomas S. Harris provided assistance with ASL data processing and analytic design. We thank Jennifer Fur-man, Ph.D. for her administrative assistance. The healthy control data, used to supplement analyses, were collected as part of the Dallas Lifespan Brain Study (http://fcon_1000.projects.nitrc.org/ indi/retro/dlbs.html), funded by R37 AG006265 (Study PI: Denise Park), R21 AG034318, and R01 MH084021 (ASL PI: Hanzhang Lu). Dr. Hanzhang Lu served as one of the EMBARC MR Physicists and the ASL consultant. Bruce Grannemann died on 9 January, 2019. We wish to dedicate this publication to him and the significant role he played in this work. Funding Information: Conflict of interest Crystal Cooper, Cherise Chin Fatt, Peiying Liu, Bruce Grannemann, Thomas Carmody, Jorge Almeida, Ashley Mal-chow, Melvin McInnis, Ramin Parsey, Elizabeth Bartlett, and Hanz-hang Lu declare that they have no conflict of interest. Thilo Deckersbach’s research has been funded by NIH, NIMH, NARSAD, TSA, IOCDF, Tufts University, DBDAT, Otsuka Pharmaceuticals, Cogito, Inc. and Sunovian. He has received honoraria, consultation fees and/or royalties from the MGH Psychiatry Academy, BrainCells Inc., Clintara, LLC., Systems Research and Applications Corporation, Boston University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, Tufts University, NIDA, NIMH, and Oxford University Press. He has also participated in research funded by DARPA, NIH, NIMH, NIA, AHRQ, PCORI, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development Inc., Medtronic, Cyberonics, Northstar, Takeda and Alpha-sigma. Maurizio 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.; Glax-oSmithKline; 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.; 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; 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; Takeda Pharmaceuticals;Tal Medical; VistaGen); Wyeth-Ayerst Laboratories; he has 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 Bio-Pharma; 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.; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, 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; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; RCT Logic, LLC (formerly Clinical Trials Solutions, LLC); 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.; Synthe-labo; Taisho Pharmaceutical; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc.; 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 equity holdings in Compellis and PsyBrain, Inc.; he has a patent for Sequential Parallel Comparison Design (SPCD), which are licensed by MGH to Pharmaceutical Product Development, LLC (PPD); and patent application for a combination of Ketamine plus Scopolamine in Major Depressive Disorder (MDD), licensed by MGH to Biohaven; and he receives copyright royalties for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), Symptoms of Depression Questionnaire (SDQ), and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing Co. Pte. Ltd. Benji Kurian has received grant support from Targacept, Inc., Pfizer, Inc., Johnson & Johnson, Evotec, Rexahn, Naurex, Forest Pharmaceuticals, and NIMH. Patrick 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). Maria Oquendo receives royalties for use of the Columbia Suicide Severity Rating Scale. Her family owns stock in Bristol-Myers Squibb. Myrna 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. Mary Phillips received funding from the National Institute of Mental Health (NIMH). Mad-hukar Trivedi is or has been an advisor/consultant and received fee from (lifetime disclosure): Abbott Laboratories Inc., Akzo (Organon Pharmaceuticals Inc.), Allergan Sales LLC, Alkermes, Arcadia Pharmaceuticals Inc., AstraZeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb Company, Cephalon Inc., Cerecor, Eli Lilly & Company, Evotec, Fabre-Kramer Pharmaceuticals Inc., Forest Pharmaceuticals, GlaxoSmithKline, Global Medical Education Inc., Health Research Associates, Johnson & Johnson, Lundbeck, MedAvante Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America Inc., MSI Methylation Sciences Inc., Nestle Health Science-PamLab Inc., Naurex, Neuronetics, One Carbon Therapeutics Ltd., Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd., Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint,
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.
AB - Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.
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UR - http://www.scopus.com/inward/citedby.url?scp=85070324067&partnerID=8YFLogxK
U2 - 10.1038/s41380-019-0464-7
DO - 10.1038/s41380-019-0464-7
M3 - Article
C2 - 31388104
AN - SCOPUS:85070324067
VL - 25
SP - 1500
EP - 1510
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 7
ER -