TY - JOUR

T1 - Resting State Networks Mediate the Effect of Genotype by Environment Interaction on Mental Health

AU - Knyazev, Gennady G.

AU - Savostyanov, Alexander N.

AU - Bocharov, Andrey V.

AU - Bazovkina, Daria V.

AU - Proshina, Ekaterina A.

N1 - Publisher Copyright: © 2017 IBRO

PY - 2018/1/15

Y1 - 2018/1/15

N2 - A number of studies have shown that the presence of short (S) allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with a higher risk for depression following exposure to stressful life events. These findings are in line with neuroimaging studies showing that 5-HTTLPR polymorphism has an effect on the connectivity among key areas involved in emotion regulation. Here using mediated moderation analysis, we show that electrophysiological manifestations of resting state networks in the alpha frequency band mediate the effect of 5-HTTLPR by stress interaction on depression/anxiety symptoms in a nonclinical sample. Specifically, at the brain level, both L-allele homozygotes and S-allele carriers are similarly responsive to stress exposure. However, these brain responses seem to act as triggers of psychopathological symptoms in S-allele carriers, but as suppressors in L-allele homozygotes. This finding implies that the interpretation of the effect of gene by environment interaction on psychopathology seems more complicated than behavioral results alone would imply. It is not just differential sensitivity to stress, but rather different ways of coping with stress, which distinguish S-allele carriers and L-allele homozygotes.

AB - A number of studies have shown that the presence of short (S) allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with a higher risk for depression following exposure to stressful life events. These findings are in line with neuroimaging studies showing that 5-HTTLPR polymorphism has an effect on the connectivity among key areas involved in emotion regulation. Here using mediated moderation analysis, we show that electrophysiological manifestations of resting state networks in the alpha frequency band mediate the effect of 5-HTTLPR by stress interaction on depression/anxiety symptoms in a nonclinical sample. Specifically, at the brain level, both L-allele homozygotes and S-allele carriers are similarly responsive to stress exposure. However, these brain responses seem to act as triggers of psychopathological symptoms in S-allele carriers, but as suppressors in L-allele homozygotes. This finding implies that the interpretation of the effect of gene by environment interaction on psychopathology seems more complicated than behavioral results alone would imply. It is not just differential sensitivity to stress, but rather different ways of coping with stress, which distinguish S-allele carriers and L-allele homozygotes.

KW - 5-HTTLPR

KW - depression

KW - EEG

KW - G × E interaction

KW - resting state networks

KW - stress

KW - INTRINSIC CONNECTIVITY NETWORKS

KW - SPONTANEOUS OSCILLATORY ACTIVITY

KW - FUNCTIONAL CONNECTIVITY

KW - DEFAULT-MODE NETWORK

KW - SEROTONIN TRANSPORTER GENE

KW - G x E interaction

KW - INDEPENDENT COMPONENT ANALYSIS

KW - ATTENTION-DEFICIT/HYPERACTIVITY DISORDER

KW - STRESSFUL LIFE EVENTS

KW - CORTICAL CORRELATION STRUCTURE

KW - MAJOR DEPRESSIVE DISORDER

KW - Humans

KW - Genetic Predisposition to Disease/genetics

KW - Male

KW - Mental Health

KW - Gene-Environment Interaction

KW - Rest/physiology

KW - Young Adult

KW - Anxiety/genetics

KW - Depression/genetics

KW - Serotonin Plasma Membrane Transport Proteins/genetics

KW - Neural Pathways/physiology

KW - Adult

KW - Female

KW - Genotype

KW - Brain/physiopathology

KW - Homozygote

KW - Stress, Psychological/genetics

KW - Heterozygote

KW - Alpha Rhythm/physiology

UR - http://www.scopus.com/inward/record.url?scp=85034961411&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2017.11.010

DO - 10.1016/j.neuroscience.2017.11.010

M3 - Article

C2 - 29129791

AN - SCOPUS:85034961411

VL - 369

SP - 139

EP - 151

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -