Genetically predicted gene expression of prefrontal DRD4 gene and the differential susceptibility to childhood emotional eating in response to positive environment

Barbara Barth; Lisiane Bizarro; Patrícia Maidana Miguel; Laurette Dubé; Robert Levitan; Kieran O'Donnell; Michael J Meaney; Patricia Pelufo Silveira

doi:10.1016/j.appet.2020.104594

Genetically predicted gene expression of prefrontal DRD4 gene and the differential susceptibility to childhood emotional eating in response to positive environment

Appetite. 2020 May 1:148:104594. doi: 10.1016/j.appet.2020.104594. Epub 2020 Jan 9.

Authors

Barbara Barth¹, Lisiane Bizarro², Patrícia Maidana Miguel³, Laurette Dubé⁴, Robert Levitan⁵, Kieran O'Donnell⁶, Michael J Meaney⁷, Patricia Pelufo Silveira⁸

Affiliations

¹ Integrated Program in Neurosciences, McGill University, 3801 University Street, Montreal, Quebec, H3A 2B4, Canada; Programa de Pós-Graduação em Psicologia, Instituto de Psicologia, Universidade Federal do Rio Grande do Sul, 2600 Ramiro Barcelos, Porto Alegre, Rio Grande do Sul, 90035003, Brazil.
² Programa de Pós-Graduação em Psicologia, Instituto de Psicologia, Universidade Federal do Rio Grande do Sul, 2600 Ramiro Barcelos, Porto Alegre, Rio Grande do Sul, 90035003, Brazil.
³ Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, 500 Sarmento Leite, Porto Alegre, Rio Grande do Sul, 90.046-900, Brazil.
⁴ Desautels Faculty of Management, McGill Center for the Convergence of Health and Economics, McGill University, 1001 Sherbrooke Street West, Montreal, Quebec, H3A 1G5, Canada.
⁵ Department of Psychiatry, University of Toronto and Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario, M5T 1R8, Canada.
⁶ Integrated Program in Neurosciences, McGill University, 3801 University Street, Montreal, Quebec, H3A 2B4, Canada; Department of Psychiatry, Faculty of Medicine and Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, 6875 Boulevard Lasalle, Montréal, Quebec, H4H 1R3, Canada.
⁷ Integrated Program in Neurosciences, McGill University, 3801 University Street, Montreal, Quebec, H3A 2B4, Canada; Department of Psychiatry, Faculty of Medicine and Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, 6875 Boulevard Lasalle, Montréal, Quebec, H4H 1R3, Canada; Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
⁸ Integrated Program in Neurosciences, McGill University, 3801 University Street, Montreal, Quebec, H3A 2B4, Canada; Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, 500 Sarmento Leite, Porto Alegre, Rio Grande do Sul, 90.046-900, Brazil; Department of Psychiatry, Faculty of Medicine and Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, 6875 Boulevard Lasalle, Montréal, Quebec, H4H 1R3, Canada. Electronic address: patricia.silveira@mcgill.ca.

PMID: 31927071
DOI: 10.1016/j.appet.2020.104594

Abstract

Genetic differential susceptibility states that individuals may vary both by exhibiting poor responses when exposed to adverse environments, and disproportionally benefiting from positive settings. The dopamine D4 receptor gene (DRD4) may be particularly implicated in these effects, including disturbed eating behaviors that might lead to obesity. Here, we explore differential susceptibility to positive environments according to the predicted genetically regulated gene expression of prefrontal cortex DRD4 gene. Using MAVAN as the discovery cohort (Maternal Adversity, Vulnerability and Neurodevelopment) and GUSTO as the replication cohort (Growing Up in Singapore Towards Healthy Outcomes), we analyzed the interaction between a) a Positive postnatal environmental score, that accounts for positive outcomes in the postnatal period and b) the genetically regulated gene expression of prefrontal DRD4, computed using a machine learning prediction method (PrediXcan). The outcome measures were the pro-intake domains (Emotional over-eating, Food Responsiveness, Food Enjoyment and Desire to Drink) from the Child Eating Behavior Questionnaire at 48 months of age (MAVAN) and 60 months of age (GUSTO). The interaction between the positive environment and the predicted prefrontal DRD4 gene expression was significant for emotional over-eating in MAVAN (β = -0.403, p < 0.02), in which the high gene expression group had more or less emotional eating according to the exposure to lower or higher positive environment respectively, showing evidence of differential susceptibility criteria. In the replication cohort, a similar result was found with the pro-intake domain Desire to drink (β = -0.583, p < 0.05). These results provide further evidence for the genetic differential susceptibility, accounting for the benefit of positive environments.

Keywords: DRD4; Differential susceptibility; Emotional eating; Gene expression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Child Behavior / psychology*
Child Development
Child, Preschool
Cohort Studies
Eating* / genetics
Eating* / psychology
Emotions*
Family Conflict
Feeding Behavior / psychology*
Female
Gene Expression
Genetic Predisposition to Disease
Humans
Hyperphagia
Infant
Infant, Newborn
Machine Learning
Male
Mother-Child Relations*
Mothers
Obesity / etiology
Obesity / genetics
Obesity / metabolism
Receptors, Dopamine D4 / genetics*
Receptors, Dopamine D4 / metabolism
Singapore
Social Environment*

Substances

Receptors, Dopamine D4