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

• Published in: European neuropsychopharmacology Vol. 29; no. 1; pp. 137 - 146
• Main Authors: Mansur, Rodrigo B., Fries, Gabriel R., Trevizol, Alisson P., Subramaniapillai, Mehala, Lovshin, Julie, Lin, Kangguang, Vinberg, Maj, Ho, Roger C., Brietzke, Elisa, McIntyre, Roger S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019
• Subjects: Adolescent; Adult; Aged; Autopsy; Body Mass Index; Brain - metabolism; Brain - pathology; Case-Control Studies; Female; Gene Expression; GLP-1R; GLP-2R; Glucagon-Like Peptide Receptors - biosynthesis; Glucagon-Like Peptide Receptors - genetics; Glucagon-Like Peptide-1 Receptor - biosynthesis; Glucagon-Like Peptide-1 Receptor - genetics; Glucagon-Like Peptide-2 Receptor - biosynthesis; Glucagon-Like Peptide-2 Receptor - genetics; Hippocampus - metabolism; Humans; Male; Middle Aged; Mood disorders; Mood Disorders - metabolism; Obesity; Prefrontal Cortex - metabolism; Psychotic Disorders - metabolism; Schizophrenia; Young Adult; Mood disorders; Schizophrenia; Obesity; Gene expression; GLP-2R; GLP-1R
• ISSN: 0924-977X; 1873-7862; 1873-7862
• DOI: 10.1016/j.euroneuro.2018.10.007

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.