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A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms.
Neuroimage Clin 2019; 22:101739NC

Abstract

Ketamine is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist. It induces effects in healthy individuals that mimic symptoms associated with schizophrenia. We sought to root these experiences in altered brain function, specifically aberrant resting state functional connectivity (rsfMRI). In the present study, we acquired rsfMRI data under ketamine and placebo in a between-subjects design and analyzed seed-based measures of rsfMRI using large-scale networks, dorsolateral prefrontal cortex (DLPFC) and sub-nuclei of the thalamus. We found ketamine-induced alterations in rsfMRI connectivity similar to those seen in patients with schizophrenia, some changes that may be more comparable to early stages of schizophrenia, and other connectivity signatures seen in patients that ketamine did not recreate. We do not find any circuits from our regions of interest that correlates with positive symptoms of schizophrenia in our sample, although we find that DLPFC connectivity with ACC does correlate with a mood measure. These results provide support for ketamine's use as a model of certain biomarkers of schizophrenia, particularly for early or at-risk patients.

Authors+Show Affiliations

Department of Psychiatry, Yale University, New Haven, CT, United States of America; Interdepartmental Neuroscience Program, Yale University, New Haven, CT, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America; Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States of America.Department of Psychiatry, University of California, Davis, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America; Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America.Department of Psychiatry, University of California, Davis, United States of America.Department of Psychiatry, University of California, Davis, United States of America.Department of Psychiatry, University of California, Davis, United States of America.Department of Psychiatry, University of California, Davis, United States of America.Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, NY, United States of America.National Institute of Mental Health, Rockville, MD, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America; National Institute of Mental Health, Rockville, MD, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States of America.Department of Psychiatry, Yale University, New Haven, CT, United States of America.Department of Psychiatry, Yale University, New Haven, CT, United States of America. Electronic address: philip.corlett@yale.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30852397

Citation

Fleming, Leah M., et al. "A Multicenter Study of Ketamine Effects On Functional Connectivity: Large Scale Network Relationships, Hubs and Symptom Mechanisms." NeuroImage. Clinical, vol. 22, 2019, p. 101739.
Fleming LM, Javitt DC, Carter CS, et al. A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. Neuroimage Clin. 2019;22:101739.
Fleming, L. M., Javitt, D. C., Carter, C. S., Kantrowitz, J. T., Girgis, R. R., Kegeles, L. S., ... Corlett, P. R. (2019). A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. NeuroImage. Clinical, 22, p. 101739. doi:10.1016/j.nicl.2019.101739.
Fleming LM, et al. A Multicenter Study of Ketamine Effects On Functional Connectivity: Large Scale Network Relationships, Hubs and Symptom Mechanisms. Neuroimage Clin. 2019;22:101739. PubMed PMID: 30852397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. AU - Fleming,Leah M, AU - Javitt,Daniel C, AU - Carter,Cameron S, AU - Kantrowitz,Joshua T, AU - Girgis,Ragy R, AU - Kegeles,Lawrence S, AU - Ragland,John D, AU - Maddock,Richard J, AU - Lesh,Tyler A, AU - Tanase,Costin, AU - Robinson,James, AU - Potter,William Z, AU - Carlson,Marlene, AU - Wall,Melanie M, AU - Choo,Tse-Hwei, AU - Grinband,Jack, AU - Lieberman,Jeffrey, AU - Krystal,John H, AU - Corlett,Philip R, Y1 - 2019/02/28/ PY - 2018/09/25/received PY - 2019/02/24/revised PY - 2019/02/27/accepted PY - 2019/3/11/pubmed PY - 2019/3/11/medline PY - 2019/3/11/entrez KW - Functional connectivity KW - Ketamine KW - Psychosis KW - Resting state SP - 101739 EP - 101739 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 22 N2 - Ketamine is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist. It induces effects in healthy individuals that mimic symptoms associated with schizophrenia. We sought to root these experiences in altered brain function, specifically aberrant resting state functional connectivity (rsfMRI). In the present study, we acquired rsfMRI data under ketamine and placebo in a between-subjects design and analyzed seed-based measures of rsfMRI using large-scale networks, dorsolateral prefrontal cortex (DLPFC) and sub-nuclei of the thalamus. We found ketamine-induced alterations in rsfMRI connectivity similar to those seen in patients with schizophrenia, some changes that may be more comparable to early stages of schizophrenia, and other connectivity signatures seen in patients that ketamine did not recreate. We do not find any circuits from our regions of interest that correlates with positive symptoms of schizophrenia in our sample, although we find that DLPFC connectivity with ACC does correlate with a mood measure. These results provide support for ketamine's use as a model of certain biomarkers of schizophrenia, particularly for early or at-risk patients. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/30852397/A_multicenter_study_of_ketamine_effects_on_functional_connectivity:_Large_scale_network_relationships_hubs_and_symptom_mechanisms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1582(19)30089-0 DB - PRIME DP - Unbound Medicine ER -