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Association between GLP-1 receptor gene polymorphisms with reward learning, anhedonia and depression diagnosis

Published online by Cambridge University Press:  26 March 2020

Hale Yapici-Eser*
School of Medicine, Koç University, İstanbul, Turkey Research Center for Translational Medicine, Koç University,İstanbul, Turkey
Vivek Appadurai
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Roskilde, Denmark
Candan Yasemin Eren
Research Center for Translational Medicine, Koç University,İstanbul, Turkey
Dilek Yazici
School of Medicine, Koç University, İstanbul, Turkey
Chia-Yen Chen
Psychiatric and Neurodevelopmental Genetics Unit and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Dost Öngür
Department of Psychiatry, Harvard Medical School, Boston, MA, USA Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, Belmont, MA, USA
Diego A. Pizzagalli
Department of Psychiatry, Harvard Medical School, Boston, MA, USA Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA
Thomas Werge
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark Institute of Biological Psychiatry, Mental Health Center St. Hans, Mental Health Services Copenhagen, Roskilde, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Mei-Hua Hall
Department of Psychiatry, Harvard Medical School, Boston, MA, USA Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, Belmont, MA, USA Psychosis Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA, USA
Author for correspondence: Hale Yapici-Eser, Email:



Glucagon-like peptide-1 receptors (GLP-1Rs) are widely expressed in the brain. Evidence suggests that they may play a role in reward responses and neuroprotection. However, the association of GLP-1R with anhedonia and depression diagnosis has not been studied. Here, we examined the association of GLP-1R polymorphisms with objective and subjective measures of anhedonia, as well as depression diagnosis.


Objective [response bias assessed by the probabilistic reward task (PRT)] and subjective [Snaith-Hamilton Pleasure Scale (SHAPS)] measures of anhedonia, clinical variables and DNA samples were collected from 100 controls and 164 patients at McLean Hospital. An independent sample genotyped as part of the Psychiatric Genomics Consortium (PGC) was used to study the effect of putative GLP-1R polymorphisms linked to response bias in PRT on depression diagnosis.


The C allele in rs1042044 was significantly associated with increased PRT response bias, when controlling for age, sex, case-control status and PRT discriminability. AA genotype of rs1042044 showed higher anhedonia phenotype based on SHAPS scores. However, analysis of PGC major depressive disorder data showed no association between rs1042044 and depression diagnosis.


Findings suggest a possible association of rs1042044 with anhedonia but no association with depression diagnosis.

Original Article
© Scandinavian College of Neuropsychopharmacology 2020

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