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

TY - JOUR

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 - Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

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 1.8mg/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.

AB - 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 1.8mg/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.

U2 - 10.1016/j.euroneuro.2017.08.433

DO - 10.1016/j.euroneuro.2017.08.433

M3 - Journal article

C2 - 28867303

SN - 0924-977X

VL - 27

SP - 1153

EP - 1162

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

IS - 11

ER -