Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders

Rodrigo B. Mansur; Andre Zugman; Juhie Ahmed; Danielle S. Cha; Mehala Subramaniapillai; Yena Lee; Julie Lovshin; Jung G. Lee; Jae Hon Lee; Vladislav Drobinin; Jason Newport; Elisa Brietzke; Eva Z. Reininghaus; Kang Sim; Maj Vinberg; Natalie Rasgon; Tomas Hajek; Roger S. McIntyre

doi:10.1016/j.euroneuro.2017.08.433

Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders

Rodrigo B. Mansur, Andre Zugman, Juhie Ahmed, Danielle S. Cha, Mehala Subramaniapillai, Yena Lee, Julie Lovshin, Jung G. Lee, Jae Hon Lee, Vladislav Drobinin, Jason Newport, Elisa Brietzke, Eva Z. Reininghaus, Kang Sim, Maj Vinberg, Natalie Rasgon, Tomas Hajek, Roger S. McIntyre

Medicine

Medicine

Résultat de recherche: Article › examen par les pairs

52 Citations (Scopus)

Résumé

Cognitive deficits are a core feature across psychiatric disorders. Emerging evidence indicates that metabolic pathways are highly relevant for the substrates and phenomenology of the cognitive domain. Herein, we aimed to determine the effects of liraglutide, a GLP−1R agonist, on brain structural/volumetric parameters in adults with a mood disorder. This is the secondary analysis of a 4-week, pilot, proof-of-concept, open-label study. Participants (N=19) exhibiting impairments in executive function with either major depressive disorder (MDD) or bipolar disorder (BD) were recruited. Liraglutide 1.8 mg/day was added as an adjunct to existing pharmacotherapy. Structural magnetic resonance imaging (MRI) scanning was obtained at baseline and endpoint. Results showed that at endpoint there was significant weight loss (mean: 3.15%; p<0.001). Changes in frontal and striatal volumes were significantly correlated with changes in body mass index (BMI), indicating the weight loss was associated with volume increase in most regions (e.g. r=−0.561, p=0.042 in the left superior frontal area). After adjusting for intracranial volume, age, gender, and BMI, we observed significant changes from baseline to endpoint in multiple regions (e.g. RR: 1.011, p=0.049 in the left rostral middle frontal area). Changes in regional volumes were associated with improvement in executive function (e.g. r=0.698, p=0.003 for the right superior frontal area). Adjunctive liraglutide results in clinically significant weight loss, with corresponding improvement in cognitive function; changes in cognitive function were partially moderated by changes in brain morphometry, underscoring the interrelationship between weight and brain structure/function.

Langue d'origine	English
Pages (de-à)	1153-1162
Nombre de pages	10
Journal	European Neuropsychopharmacology
Volume	27
Numéro de publication	11
DOI	https://doi.org/10.1016/j.euroneuro.2017.08.433
Statut de publication	Published - nov. 2017

Note bibliographique

Funding Information:
The study was funded by the Brain and Cognition Discovery Foundation (BCDF) and did not receive any external funding from the manufacturer of liraglutide. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Funding Information:
RBM has received support from FAPESP, Brazil and fellowship funding from Lundbeck, Canada. AZ has received support from CAPES/CNPq, Brazil. JL is supported by an Eliot Phillipson Clinician Scientist Fellowship Award, Department of Medicine, University of Toronto and has received speaker's honoraria from Novo Nordisk. EB received research grants from CNPq, FAPESP, CAPES, Brazil and from L’Oreal/ Brazilian Academy of Sciences/UNESCO For Women in Science Award. She had received honoraria as speaker/consultant from Eurofarma, Daiichi-Sankyo and Achè. MV has within the preceding three years been a consultant for AstraZeneca, and Lundbeck. NR has received grant/research Support from Piramal and Novo-Nordisk; and consulting fees from Sunovion Pharmaceuticals, Takeda Pharmaceuticals, and Shire Pharmaceuticals. RSM has served as an advisor or consultant for AstraZeneca, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Merck & Co., Organon, Pfizer and Shire; has served as a speaker or a member of a speakers bureau for AstraZeneca, Lilly, Janssen-Ortho, Lundbeck, Merck & Co. and Pfizer; and has received grants for clinical research from AstraZeneca, Lilly, Janssen-Ortho, Lundbeck, Pfizer and Shire. JA, DS, MS, YL, JGL, JHL, VD, JN, EZR, KS and TH have no financial conflicts of interest.

Publisher Copyright:
© 2017 Elsevier B.V. and ECNP

ASJC Scopus Subject Areas

Pharmacology
Neurology
Clinical Neurology
Psychiatry and Mental health
Biological Psychiatry
Pharmacology (medical)

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

Accès au document

10.1016/j.euroneuro.2017.08.433

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Mansur, R. B., Zugman, A., Ahmed, J., Cha, D. S., Subramaniapillai, M., Lee, Y., Lovshin, J., Lee, J. G., Lee, J. H., Drobinin, V., Newport, J., Brietzke, E., Reininghaus, E. Z., Sim, K., Vinberg, M., Rasgon, N., Hajek, T., & McIntyre, R. S. (2017). Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders. European Neuropsychopharmacology, 27(11), 1153-1162. https://doi.org/10.1016/j.euroneuro.2017.08.433

Mansur, RB, Zugman, A, Ahmed, J, Cha, DS, Subramaniapillai, M, Lee, Y, Lovshin, J, Lee, JG, Lee, JH, Drobinin, V, Newport, J, Brietzke, E, Reininghaus, EZ, Sim, K, Vinberg, M, Rasgon, N, Hajek, T & McIntyre, RS 2017, 'Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders', European Neuropsychopharmacology, vol. 27, n° 11, pp. 1153-1162. https://doi.org/10.1016/j.euroneuro.2017.08.433

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title = "Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders",

abstract = "Cognitive deficits are a core feature across psychiatric disorders. Emerging evidence indicates that metabolic pathways are highly relevant for the substrates and phenomenology of the cognitive domain. Herein, we aimed to determine the effects of liraglutide, a GLP−1R agonist, on brain structural/volumetric parameters in adults with a mood disorder. This is the secondary analysis of a 4-week, pilot, proof-of-concept, open-label study. Participants (N=19) exhibiting impairments in executive function with either major depressive disorder (MDD) or bipolar disorder (BD) were recruited. Liraglutide 1.8 mg/day was added as an adjunct to existing pharmacotherapy. Structural magnetic resonance imaging (MRI) scanning was obtained at baseline and endpoint. Results showed that at endpoint there was significant weight loss (mean: 3.15%; p<0.001). Changes in frontal and striatal volumes were significantly correlated with changes in body mass index (BMI), indicating the weight loss was associated with volume increase in most regions (e.g. r=−0.561, p=0.042 in the left superior frontal area). After adjusting for intracranial volume, age, gender, and BMI, we observed significant changes from baseline to endpoint in multiple regions (e.g. RR: 1.011, p=0.049 in the left rostral middle frontal area). Changes in regional volumes were associated with improvement in executive function (e.g. r=0.698, p=0.003 for the right superior frontal area). Adjunctive liraglutide results in clinically significant weight loss, with corresponding improvement in cognitive function; changes in cognitive function were partially moderated by changes in brain morphometry, underscoring the interrelationship between weight and brain structure/function.",

author = "Mansur, {Rodrigo B.} and Andre Zugman and Juhie Ahmed and Cha, {Danielle S.} and Mehala Subramaniapillai and Yena Lee and Julie Lovshin and Lee, {Jung G.} and Lee, {Jae Hon} and Vladislav Drobinin and Jason Newport and Elisa Brietzke and Reininghaus, {Eva Z.} and Kang Sim and Maj Vinberg and Natalie Rasgon and Tomas Hajek and McIntyre, {Roger S.}",

note = "Funding Information: The study was funded by the Brain and Cognition Discovery Foundation (BCDF) and did not receive any external funding from the manufacturer of liraglutide. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: RBM has received support from FAPESP, Brazil and fellowship funding from Lundbeck, Canada. AZ has received support from CAPES/CNPq, Brazil. JL is supported by an Eliot Phillipson Clinician Scientist Fellowship Award, Department of Medicine, University of Toronto and has received speaker's honoraria from Novo Nordisk. EB received research grants from CNPq, FAPESP, CAPES, Brazil and from L{\textquoteright}Oreal/ Brazilian Academy of Sciences/UNESCO For Women in Science Award. She had received honoraria as speaker/consultant from Eurofarma, Daiichi-Sankyo and Ach{\`e}. MV has within the preceding three years been a consultant for AstraZeneca, and Lundbeck. NR has received grant/research Support from Piramal and Novo-Nordisk; and consulting fees from Sunovion Pharmaceuticals, Takeda Pharmaceuticals, and Shire Pharmaceuticals. RSM has served as an advisor or consultant for AstraZeneca, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Merck & Co., Organon, Pfizer and Shire; has served as a speaker or a member of a speakers bureau for AstraZeneca, Lilly, Janssen-Ortho, Lundbeck, Merck & Co. and Pfizer; and has received grants for clinical research from AstraZeneca, Lilly, Janssen-Ortho, Lundbeck, Pfizer and Shire. JA, DS, MS, YL, JGL, JHL, VD, JN, EZR, KS and TH have no financial conflicts of interest. Publisher Copyright: {\textcopyright} 2017 Elsevier B.V. and ECNP",

year = "2017",

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doi = "10.1016/j.euroneuro.2017.08.433",

language = "English",

volume = "27",

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T1 - Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders

AU - Mansur, Rodrigo B.

AU - Zugman, Andre

AU - Ahmed, Juhie

AU - Cha, Danielle S.

AU - Subramaniapillai, Mehala

AU - Lee, Yena

AU - Lovshin, Julie

AU - Lee, Jung G.

AU - Lee, Jae Hon

AU - Drobinin, Vladislav

AU - Newport, Jason

AU - Brietzke, Elisa

AU - Reininghaus, Eva Z.

AU - Sim, Kang

AU - Vinberg, Maj

AU - Rasgon, Natalie

AU - Hajek, Tomas

AU - McIntyre, Roger S.

N1 - Funding Information: The study was funded by the Brain and Cognition Discovery Foundation (BCDF) and did not receive any external funding from the manufacturer of liraglutide. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: RBM has received support from FAPESP, Brazil and fellowship funding from Lundbeck, Canada. AZ has received support from CAPES/CNPq, Brazil. JL is supported by an Eliot Phillipson Clinician Scientist Fellowship Award, Department of Medicine, University of Toronto and has received speaker's honoraria from Novo Nordisk. EB received research grants from CNPq, FAPESP, CAPES, Brazil and from L’Oreal/ Brazilian Academy of Sciences/UNESCO For Women in Science Award. She had received honoraria as speaker/consultant from Eurofarma, Daiichi-Sankyo and Achè. MV has within the preceding three years been a consultant for AstraZeneca, and Lundbeck. NR has received grant/research Support from Piramal and Novo-Nordisk; and consulting fees from Sunovion Pharmaceuticals, Takeda Pharmaceuticals, and Shire Pharmaceuticals. RSM has served as an advisor or consultant for AstraZeneca, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Merck & Co., Organon, Pfizer and Shire; has served as a speaker or a member of a speakers bureau for AstraZeneca, Lilly, Janssen-Ortho, Lundbeck, Merck & Co. and Pfizer; and has received grants for clinical research from AstraZeneca, Lilly, Janssen-Ortho, Lundbeck, Pfizer and Shire. JA, DS, MS, YL, JGL, JHL, VD, JN, EZR, KS and TH have no financial conflicts of interest. Publisher Copyright: © 2017 Elsevier B.V. and ECNP

PY - 2017/11

Y1 - 2017/11

N2 - Cognitive deficits are a core feature across psychiatric disorders. Emerging evidence indicates that metabolic pathways are highly relevant for the substrates and phenomenology of the cognitive domain. Herein, we aimed to determine the effects of liraglutide, a GLP−1R agonist, on brain structural/volumetric parameters in adults with a mood disorder. This is the secondary analysis of a 4-week, pilot, proof-of-concept, open-label study. Participants (N=19) exhibiting impairments in executive function with either major depressive disorder (MDD) or bipolar disorder (BD) were recruited. Liraglutide 1.8 mg/day was added as an adjunct to existing pharmacotherapy. Structural magnetic resonance imaging (MRI) scanning was obtained at baseline and endpoint. Results showed that at endpoint there was significant weight loss (mean: 3.15%; p<0.001). Changes in frontal and striatal volumes were significantly correlated with changes in body mass index (BMI), indicating the weight loss was associated with volume increase in most regions (e.g. r=−0.561, p=0.042 in the left superior frontal area). After adjusting for intracranial volume, age, gender, and BMI, we observed significant changes from baseline to endpoint in multiple regions (e.g. RR: 1.011, p=0.049 in the left rostral middle frontal area). Changes in regional volumes were associated with improvement in executive function (e.g. r=0.698, p=0.003 for the right superior frontal area). Adjunctive liraglutide results in clinically significant weight loss, with corresponding improvement in cognitive function; changes in cognitive function were partially moderated by changes in brain morphometry, underscoring the interrelationship between weight and brain structure/function.

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Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders

Résumé

Note bibliographique

ASJC Scopus Subject Areas

ODD de l’ONU

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