A systematic review in effects of glucagon-like peptide-1 (GLP-1) mono-agonists on functional connectivity: Target engagement and rationale for the development in mental disorders.

Autor: Au HCT; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: hezekiah.au@mail.utoronto.ca., Zheng YJ; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: yangjing.zheng@mail.utoronto.ca., Le GH; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: hanny.le@mail.utoronto.ca., Wong S; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: sabrinal.wong@mail.utoronto.ca., Phan L; Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada. Electronic address: lee.phan@mail.utoronto.ca., Teopiz KM; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. Electronic address: kayla.teopiz@mail.utoronto.ca., Kwan ATH; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. Electronic address: angela.kwan@mail.utoronto.ca., Rhee TG; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Department of Public Health Sciences, University of Connecticut School of Medicine, Farmington, CT, USA. Electronic address: taeho.rhee@yale.edu., Rosenblat JD; Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: joshua.rosenblat@uhn.ca., Ho R; Division of Life Science (LIFS), Faculty of Science, Hong Kong University of Science and Technology (HKUST), Hong Kong; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: rogercmho@ust.hk., McIntyre RS; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: roger.mcintyre@bcdf.org.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2025 Feb 01; Vol. 370, pp. 321-327. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1016/j.jad.2024.11.019
Abstrakt: Introduction: The mechanistic role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) in modulating brain functional activity has been inadequately examined. Mental disorders are characterized by dysregulated functional connectivity in brain circuits that subserve phenomenology. We conducted a comprehensive synthesis of known effects of GLP-1 and GLP-1RAs on functional connectivity.
Methods: We conducted a systematic review examining studies that investigate changes in functional connectivity mediated by GLP-1 and GLP-1RAs in human adults. Relevant articles were retrieved from OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to April 26, 2024. Primary or secondary studies (n = 8) investigating the role of GLP-1 and GLP-1RAs on functional connectivity were included for analysis.
Results: GLP-1 and GLP-1RAs modulate functional connectivity within the dorsal default mode network (DMN), visuospatial network, right frontal parietal network, and the salience network. GLP-1 agonism is also associated with decreased functional connectivity within the hypothalamus, lateral orbitofrontal cortex, and amygdala. Contrastingly, some GLP-1RAs (e.g. exenatide) increase functional connectivity in the hypothalamus, nucleus tractus solitarius, and thalamus. Moreover, liraglutide is associated with increased functional connectivity within the hippocampus in healthy individuals suggesting that GLP-1RAs may have differential effects on brain functional connectivity.
Discussion: We observed that GLP-1 and GLP-1 RAs are associated with changes in functional connectivity known to subserve phenomenology of many mental disorders (e.g. anhedonia). Future research should aim to further examine neural circuits and networks affected by GLP-1 receptor activity and how they may affect cognitive and psychopathological domains in psychiatric disorders.
Competing Interests: Declaration of competing interest Kayla M. Teopiz has received fees from Braxia Scientific Corp. Dr. Taeho Greg Rhee was supported in part by the National Institute on Aging (#R21AG070666; R21AG078972; R01AG088647), National Institute of Mental Health (#R01MH131528), and National Institute on Drug Abuse (#R21DA057540). Dr. Rhee serves as a review committee member for Patient-Centered Outcomes Research Institute (PCORI) and Substance Abuse and Mental Health Services Administration (SAMHSA) and has received honoraria payments from PCORI and SAMHSA. Dr. Rhee has also served as a stakeholder/consultant for PCORI and received consulting fees from PCORI. Dr. Rhee serves as an advisory committee member for International Alliance of Mental Health Research Funders (IAMHRF). Dr. Joshua D Rosenblat has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services Inc. (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion and COMPASS. He is the Chief Medical and Scientific Officer of Braxia Scientific and the medical director of the Canadian Rapid Treatment Centre of Excellence (Braxia Health). Dr. Roger Ho received funding from the National University of Singapore iHealthtech Other Operating Expenses (A-0001415-09-00). Dr. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Hezekiah C.T. Au, Yang Jing Zheng, Gia Han Le, Sabrina Wong, Lee Phan, and Angela T.H. Kwan have no conflicts of interests to declare.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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