Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.

Autor:	Moujaes F; Department of Psychiatry, Yale University School of Medicine, New Haven, United States.; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Zurich, Switzerland., Ji JL; Department of Psychiatry, Yale University School of Medicine, New Haven, United States., Rahmati M; Department of Psychiatry, Yale University School of Medicine, New Haven, United States., Burt JB; Department of Physics, Yale University, Boston, United States., Schleifer C; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States., Adkinson BD; Interdepartmental Neuroscience Program, Yale University, New Haven, United States., Savic A; Department of Psychiatry, University of Zagreb, Zagreb, Croatia., Santamauro N; Department of Psychiatry, Yale University School of Medicine, New Haven, United States., Tamayo Z; Department of Psychiatry, Yale University School of Medicine, New Haven, United States., Diehl C; Department of Psychology, University of California, Los Angeles, Los Angeles, United States., Kolobaric A; Center of Neuroscience, University of Pittsburgh, Pittsburgh, United States., Flynn M; Department of Psychiatry, Vanderbilt University Medical Center, Nashville, United States., Rieser N; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Zurich, Switzerland., Fonteneau C; Department of Psychiatry, Yale University School of Medicine, New Haven, United States., Camarro T; Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, United States., Xu J; Department of Radiology and Psychiatry, Baylor College of Medicine, Houston, United States., Cho Y; Department of Psychiatry, Yale University School of Medicine, New Haven, United States.; Child Study Center, Yale University School of Medicine, New Haven, United States., Repovs G; Department of Psychology, University of Ljubljana, Ljubljana, Slovenia., Fineberg SK; Department of Psychiatry, Yale University School of Medicine, New Haven, United States., Morgan PT; Department of Psychiatry, Yale University School of Medicine, New Haven, United States.; Department of Psychiatry, Bridgeport Hospital, Bridgeport, United States., Seifritz E; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Zurich, Switzerland., Vollenweider FX; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Zurich, Switzerland., Krystal JH; Department of Psychiatry, Yale University School of Medicine, New Haven, United States., Murray JD; Department of Psychiatry, Yale University School of Medicine, New Haven, United States.; Department of Physics, Yale University, Boston, United States.; Department of Psychology, Yale University, New Haven, United States., Preller KH; Department of Psychiatry, Yale University School of Medicine, New Haven, United States.; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Zurich, Switzerland., Anticevic A; Department of Psychiatry, Yale University School of Medicine, New Haven, United States.; Interdepartmental Neuroscience Program, Yale University, New Haven, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Apr 17; Vol. 13. Date of Electronic Publication: 2024 Apr 17.
DOI:	10.7554/eLife.84173
Abstrakt:	Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. Results: We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. Funding: This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016-0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 - 2056) (FXV). Clinical Trial Number: NCT03842800. Competing Interests: FM, MR, CS, BA, AS, NS, CD, AK, MF, NR, TC, JX, YC, PM, ES, FV No competing interests declared, JJ J.L.J. is an employee of Manifest Technologies and has previously worked for Neumora (formerly BlackThorn Therapeutics) and is a co-inventor on the following patent: Anticevic A, Murray JD, Ji JL: Systems and Methods for Neuro-Behavioral Relationships in Dimensional Geometric Embedding (N-BRIDGE), PCT International Application No. PCT/US2119/022110, filed March 13, 2019, JB Currently an employee of Neumora Therapeutics and consulted for BlackThorn Therapeutics in 2019, ZT, CF Consults for Manifest Technologies and previously consulted for Neumora (formerly BlackThorn Therapeutics), GR Consults for and holds equity with RBNC (formerly BlackThorn Therapeutics), SF Sarah K. Fineberg: discloses work with the pharmaceutical company Boehringer Ingelheim as site PI for a multinational clinical trial and for consulting on advisory boards (< $10,000 in 2022), JK Was a consultant for Aptinyx, Atai Life Sciences, AstraZeneca Pharmaceuticals, Biogen Idec, Biomedisyn Corporation, Bionomics, Limited, Boehringer Ingelheim International, Cadent Therapeutics, Clexio Bioscience, COMPASS Pathways, Limited, Concert Pharmaceuticals, Epiodyne, EpiVario, Greenwich Biosciences, Heptares Therapeutics, Limited (UK), Janssen Research \& Development, Jazz Pharmaceuticals, Otsuka America Pharmaceutical, Perception Neuroscience Holdings, Spring Care, Sunovion Pharmaceuticals, Takeda Industries, Taisho Pharmaceutical Co. He served on advisory boards for Biohaven Pharmaceuticals, BioXcel Therapeutics, BlackThorn Therapeutics, Cadent Therapeutics, Cerevel Therapeutics, EpiVario, Eisai, Lohocla Research Corporation, Novartis Pharmaceuticals Corporation, PsychoGenics, Tempero Bio, and Terran Biosciences. He owns stock or stock options in Biohaven Pharmaceuticals, Sage Pharmaceuticals, Spring Care, Biohaven Pharmaceuticals Medical Sciences, BlackThorn Therapeutics, EpiVario, Terran Biosciences, and Tempero Bio, and he is on the editorial board of Biological Psychiatry, JM Consults for and holds equity with RBNC (formerly BlackThorn Therapeutics) and is a coinventor on the following patents: Anticevic A, Murray JD, Ji JL: Systems and Methods for Neuro-Behavioral Relationships in Dimensional Geometric Embedding (N-BRIDGE), PCT International Application No. PCT/US2119/022110, filed March 13, 2019 and Murray JD, Anticevic A, Martin, WJ: Methods and tools for detecting, diagnosing, predicting, prognosticating, or treating a neurobehavioral phenotype in a subject, U.S. Application No. 16/149,903 filed on October 2, 2018, U.S. Application or PCT International Application No. 18/054,009 filed on October 2, 2018, KP Currently an employee of by Boehringer Ingelheim GmBH \& CO KG, AA Consults for and holds equity with RBNC (formerly BlackThorn Therapeutics) and is a coinventor on the following patents: Anticevic A, Murray JD, Ji JL: Systems and Methods for Neuro-Behavioral Relationships in Dimensional Geometric Embedding (N-BRIDGE), PCT International Application No. PCT/US2119/022110, filed March 13, 2019 and Murray JD, Anticevic A, Martin, WJ: Methods and tools for detecting, diagnosing, predicting, prognosticating, or treating a neurobehavioral phenotype in a subject, U.S. Application No. 16/149,903 filed on October 2, 2018, U.S. Application for PCT International Application No. 18/054,009 filed on October 2, 2018 (© 2024, Moujaes, Ji et al.)
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