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. 2019 Jan;29(1):137-146.
doi: 10.1016/j.euroneuro.2018.10.007. Epub 2018 Nov 6.

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  1 , Gabriel R Fries  2 , Alisson P Trevizol  3 , Mehala Subramaniapillai  4 , Julie Lovshin  5 , Kangguang Lin  6 , Maj Vinberg  7 , Roger C Ho  8 , Elisa Brietzke  9 , Roger S McIntyre  10
Affiliations

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 et al. Eur Neuropsychopharmacol. 2019 Jan.

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.

Trial registration: ClinicalTrials.gov NCT00001260.

Keywords: GLP-1R; GLP-2R; Gene expression; Mood disorders; Obesity; Schizophrenia.

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Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interest related to this work.

Figures

Figure 1–
Figure 1–
Associations between body mass index and (A) GLP-1R and (B) GLP-2R gene expression, according to diagnosis, in the dorsolateral prefrontal cortex. HC: healthy controls; SCZ: schizophrenia; MD: mood disorders.
Figure 2–
Figure 2–
Associations between body mass index and (A) GLP-1R and (B) GLP-2R gene expression, according to diagnosis, in the hippocampus. HC: healthy controls; SCZ: schizophrenia; MD: mood disorders
See this image and copyright information in PMC

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