Linking genetic variants of the mineralocorticoid receptor and negative memory bias: interaction with prior life adversity.
Substantial research has been conducted investigating the association between life adversity and genetic vulnerability for depression, but clear mechanistic links are rarely identified and investigation often focused on single genetic variants. Complex phenotypes like depression, however, are likely determined by multiple variants in interaction with environmental factors. As variations in the mineralocorticoid receptor gene (NR3C2) have been related to a higher risk for depression, we investigated whether NR3C2 variance is related to negative memory bias, an established endophenotype for depression, in healthy participants. Furthermore, we explored the influence of life adversity on this association. We used a set-based analysis to simultaneously test all measured variation in NR3C2 for an association with negative memory bias in 483 participants and an interaction with life adversity. To further specify this interaction, we split the sample into low and high live adversity groups and repeated the analyses in both groups separately. NR3C2 variance was associated with negative memory bias, especially in the high life adversity group. Additionally, we identified a functional polymorphism (rs5534) related to negative memory bias and demonstrating a gene×life adversity interaction. Variations in NR3C2 are associated with negative memory bias and this relationship appears to be influenced by life adversity. As negative memory bias is implicated in the susceptibility to depression, our findings provide mechanistic support for the notion that variations in NR3C2 - which could compromise the proper function of this receptor - are a risk factor for the development of mood disorders.
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Cognitive Neuroscience, Nijmegen, The Netherlands. Electronic address: s.vogel@donders.ru.nl.
Susanne
S
Vogel
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Karolinska Institute, Department of Medical Epidemiology and Biostatistics, Solna, Sweden.
Lotte
L
Gerritsen
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Psychiatry, Nijmegen, The Netherlands.
Iris
I
van Oostrom
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Psychiatry, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
Alejandro
A
Arias-Vásquez
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Mark
M
Rijpkema
University Medical Centre Utrecht, Rudolf Magnus Institute of Neuroscience, The Netherlands.
Marian
M
Joëls
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Psychiatry, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands.
Barbara
B
Franke
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Psychiatry, Nijmegen, The Netherlands; University of Duisburg-Essen, LVR Clinics of Psychiatry and Psychotherapy, Essen, Germany.
Indira
I
Tendolkar
Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Radboud University Nijmegen Medical Centre, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
Guillén
G
Fernández
D000293:Adolescent; D000328:Adult; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008016:Life Change Events; D008297:Male; D008568:Memory; D019964:Mood Disorders / Q000235:genetics; D009341:Negativism; D020641:Polymorphism, Single Nucleotide; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D055815:Young Adult
C561839:NR3C2 protein, human; D018161:Receptors, Mineralocorticoid
Gene×life adversity interaction; Memory bias; Mineralocorticoid receptor; NR3C2