The effect of body mass index on glucagon-like peptide receptor gene expression in the post mortem brain from individuals with mood and psychotic disorders

Rodrigo B. Mansur; Gabriel R. Fries; Alisson P. Trevizol; Mehala Subramaniapillai; Julie Lovshin; Kangguang Lin; Maj Vinberg; Roger C. Ho; Elisa Brietzke; Roger S. McIntyre

doi:10.1016/j.euroneuro.2018.10.007

The effect of body mass index on glucagon-like peptide receptor gene expression in the post mortem brain from individuals with mood and psychotic disorders

Rodrigo B. Mansur^*, Gabriel R. Fries, Alisson P. Trevizol, Mehala Subramaniapillai, Julie Lovshin, Kangguang Lin, Maj Vinberg, Roger C. Ho, Elisa Brietzke, Roger S. McIntyre

^*Corresponding author for this work

Department of Clinical Medicine

8 Citations (Scopus)

Abstract

There is an increasing interest in the putative role of glucagon-like peptide 1 receptor (GLP-1R) agonists as novel therapeutic agents for mental disorders. Herein, we investigated the expressions of GLP-1R and GLP-2R genes, and its relationship with body mass index (BMI), in the post-mortem brain tissue of patients with mood (MD) and psychotic disorders. Brain samples were localized to the dorsolateral prefrontal cortex (dlPFC) (n = 459) and hippocampus (n = 378). After adjustment for age, sex, ethnicity, post-mortem interval (PMI) and BMI, we observed significant differences, between healthy controls and MD subjects, in GLP-1R and GLP-2R gene expression in the dlPFC (β = 1.504, p = 0.004; and β = 1.305, p = 0.011, respectively); whereas in the hippocampus, only GLP-1R expression was significantly associated with MD (β = −1.28, p = 0.029). No significant differences were found in relation to schizophrenia. In addition, we observed a moderating effect of MD diagnosis on the associations between BMI, GLP-1R and GLP-2R expression values in the dlPFC (β = −0.05, p = 0.003; and β = −0.04, p = 0.004, respectively). There was a similar moderating effect for GLP-1R in the hippocampus (β = 0.043, 95% CI 0.003; 0.08 p = 0.03), but in an opposite direction than observed in the dlPFC. This is the first evidence of abnormal gene expression of GLP-1R and GLP-2R in postmortem brain of individuals with MD, providing a rationale for further inquiry and proof of principle interventional studies.

Original language	English
Journal	European Neuropsychopharmacology
Volume	29
Issue number	1
Pages (from-to)	137-146
Number of pages	10
ISSN	0924-977X
DOIs	https://doi.org/10.1016/j.euroneuro.2018.10.007
Publication status	Published - 2019

Keywords

Gene expression
GLP-1R
GLP-2R
Mood disorders
Obesity
Schizophrenia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.euroneuro.2018.10.007

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Mansur, R. B., Fries, G. R., Trevizol, A. P., Subramaniapillai, M., Lovshin, J., Lin, K., Vinberg, M., Ho, R. C., Brietzke, E., & McIntyre, R. S. (2019). The effect of body mass index on glucagon-like peptide receptor gene expression in the post mortem brain from individuals with mood and psychotic disorders. European Neuropsychopharmacology, 29(1), 137-146. https://doi.org/10.1016/j.euroneuro.2018.10.007

The effect of body mass index on glucagon-like peptide receptor gene expression in the post mortem brain from individuals with mood and psychotic disorders. / Mansur, Rodrigo B.; Fries, Gabriel R.; Trevizol, Alisson P. et al.

In: European Neuropsychopharmacology, Vol. 29, No. 1, 2019, p. 137-146.

Research output: Contribution to journal › Journal article › Research › peer-review

Mansur, RB, Fries, GR, Trevizol, AP, Subramaniapillai, M, Lovshin, J, Lin, K, Vinberg, M, Ho, RC, Brietzke, E & McIntyre, RS 2019, 'The effect of body mass index on glucagon-like peptide receptor gene expression in the post mortem brain from individuals with mood and psychotic disorders', European Neuropsychopharmacology, vol. 29, no. 1, pp. 137-146. https://doi.org/10.1016/j.euroneuro.2018.10.007

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abstract = "There is an increasing interest in the putative role of glucagon-like peptide 1 receptor (GLP-1R) agonists as novel therapeutic agents for mental disorders. Herein, we investigated the expressions of GLP-1R and GLP-2R genes, and its relationship with body mass index (BMI), in the post-mortem brain tissue of patients with mood (MD) and psychotic disorders. Brain samples were localized to the dorsolateral prefrontal cortex (dlPFC) (n = 459) and hippocampus (n = 378). After adjustment for age, sex, ethnicity, post-mortem interval (PMI) and BMI, we observed significant differences, between healthy controls and MD subjects, in GLP-1R and GLP-2R gene expression in the dlPFC (β = 1.504, p = 0.004; and β = 1.305, p = 0.011, respectively); whereas in the hippocampus, only GLP-1R expression was significantly associated with MD (β = −1.28, p = 0.029). No significant differences were found in relation to schizophrenia. In addition, we observed a moderating effect of MD diagnosis on the associations between BMI, GLP-1R and GLP-2R expression values in the dlPFC (β = −0.05, p = 0.003; and β = −0.04, p = 0.004, respectively). There was a similar moderating effect for GLP-1R in the hippocampus (β = 0.043, 95% CI 0.003; 0.08 p = 0.03), but in an opposite direction than observed in the dlPFC. This is the first evidence of abnormal gene expression of GLP-1R and GLP-2R in postmortem brain of individuals with MD, providing a rationale for further inquiry and proof of principle interventional studies.",

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author = "Mansur, {Rodrigo B.} and Fries, {Gabriel R.} and Trevizol, {Alisson P.} and Mehala Subramaniapillai and Julie Lovshin and Kangguang Lin and Maj Vinberg and Ho, {Roger C.} and Elisa Brietzke and McIntyre, {Roger S.}",

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AU - Mansur, Rodrigo B.

AU - Fries, Gabriel R.

AU - Trevizol, Alisson P.

AU - Subramaniapillai, Mehala

AU - Lovshin, Julie

AU - Lin, Kangguang

AU - Vinberg, Maj

AU - Ho, Roger C.

AU - Brietzke, Elisa

AU - McIntyre, Roger S.

PY - 2019

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N2 - There is an increasing interest in the putative role of glucagon-like peptide 1 receptor (GLP-1R) agonists as novel therapeutic agents for mental disorders. Herein, we investigated the expressions of GLP-1R and GLP-2R genes, and its relationship with body mass index (BMI), in the post-mortem brain tissue of patients with mood (MD) and psychotic disorders. Brain samples were localized to the dorsolateral prefrontal cortex (dlPFC) (n = 459) and hippocampus (n = 378). After adjustment for age, sex, ethnicity, post-mortem interval (PMI) and BMI, we observed significant differences, between healthy controls and MD subjects, in GLP-1R and GLP-2R gene expression in the dlPFC (β = 1.504, p = 0.004; and β = 1.305, p = 0.011, respectively); whereas in the hippocampus, only GLP-1R expression was significantly associated with MD (β = −1.28, p = 0.029). No significant differences were found in relation to schizophrenia. In addition, we observed a moderating effect of MD diagnosis on the associations between BMI, GLP-1R and GLP-2R expression values in the dlPFC (β = −0.05, p = 0.003; and β = −0.04, p = 0.004, respectively). There was a similar moderating effect for GLP-1R in the hippocampus (β = 0.043, 95% CI 0.003; 0.08 p = 0.03), but in an opposite direction than observed in the dlPFC. This is the first evidence of abnormal gene expression of GLP-1R and GLP-2R in postmortem brain of individuals with MD, providing a rationale for further inquiry and proof of principle interventional studies.

AB - There is an increasing interest in the putative role of glucagon-like peptide 1 receptor (GLP-1R) agonists as novel therapeutic agents for mental disorders. Herein, we investigated the expressions of GLP-1R and GLP-2R genes, and its relationship with body mass index (BMI), in the post-mortem brain tissue of patients with mood (MD) and psychotic disorders. Brain samples were localized to the dorsolateral prefrontal cortex (dlPFC) (n = 459) and hippocampus (n = 378). After adjustment for age, sex, ethnicity, post-mortem interval (PMI) and BMI, we observed significant differences, between healthy controls and MD subjects, in GLP-1R and GLP-2R gene expression in the dlPFC (β = 1.504, p = 0.004; and β = 1.305, p = 0.011, respectively); whereas in the hippocampus, only GLP-1R expression was significantly associated with MD (β = −1.28, p = 0.029). No significant differences were found in relation to schizophrenia. In addition, we observed a moderating effect of MD diagnosis on the associations between BMI, GLP-1R and GLP-2R expression values in the dlPFC (β = −0.05, p = 0.003; and β = −0.04, p = 0.004, respectively). There was a similar moderating effect for GLP-1R in the hippocampus (β = 0.043, 95% CI 0.003; 0.08 p = 0.03), but in an opposite direction than observed in the dlPFC. This is the first evidence of abnormal gene expression of GLP-1R and GLP-2R in postmortem brain of individuals with MD, providing a rationale for further inquiry and proof of principle interventional studies.

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KW - GLP-1R

KW - GLP-2R

KW - Mood disorders

KW - Obesity

KW - Schizophrenia

U2 - 10.1016/j.euroneuro.2018.10.007

DO - 10.1016/j.euroneuro.2018.10.007

M3 - Journal article

C2 - 30409537

AN - SCOPUS:85055974608

SN - 0924-977X

VL - 29

SP - 137

EP - 146

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

IS - 1

ER -

The effect of body mass index on glucagon-like peptide receptor gene expression in the post mortem brain from individuals with mood and psychotic disorders

Abstract

Keywords

UN SDGs

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