Interactive effect of 5-HTTLPR and BDNF polymorphisms on amygdala intrinsic functional connectivity and anxiety.
Adolescent
Amygdala
/ diagnostic imaging
Anxiety
/ diagnostic imaging
Brain-Derived Neurotrophic Factor
/ genetics
Epistasis, Genetic
/ physiology
Female
Humans
Magnetic Resonance Imaging
/ methods
Male
Nerve Net
/ diagnostic imaging
Polymorphism, Genetic
/ genetics
Prefrontal Cortex
/ diagnostic imaging
Serotonin Plasma Membrane Transport Proteins
/ genetics
Young Adult
5-HTTLPR
Amygdala
Anxiety
Brain-derived neurotrophic factor
Intrinsic functional connectivity
fMRI
Journal
Psychiatry research. Neuroimaging
ISSN: 1872-7506
Titre abrégé: Psychiatry Res Neuroimaging
Pays: Netherlands
ID NLM: 101723001
Informations de publication
Date de publication:
30 03 2019
30 03 2019
Historique:
received:
29
06
2018
revised:
28
01
2019
accepted:
28
01
2019
pubmed:
4
2
2019
medline:
12
2
2020
entrez:
4
2
2019
Statut:
ppublish
Résumé
The serotonin transporter (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) gene polymorphisms have been associated with risk for affective disorders and functional variability of the amygdala. We examined whether the two genotypes interactively influence intrinsic functional connectivity (FC) of the amygdala and whether FC mediates the genetic association with anxiety. Eighty genotyped healthy adults underwent resting state fMRI and completed the self-reported State-Trait Anxiety Inventory. Interactive genetic association with anxiety was observed such that effects of 5-HTTLPR depended on the BDNF Val66Met polymorphism (rs6265 variant), with higher anxiety scores in short and Met carriers compared to the other allelic groups. Voxel-wise FC with left and right amygdala seeds identified regions that were sensitive to variability in anxiety scores. A significant moderated mediation model demonstrated that the effect of 5-HTTLPR genotype on anxiety, moderated by BDNF Val66Met genotype, was fully mediated by FC between the left amygdala and the right dorsolateral prefrontal cortex, a cognitive control-related region, during a task-free state. FC was highest in carriers of the 5-HTTLPR short allele and BDNF Met allele. These findings establish intrinsic amygdala-prefrontal functional connectivity as a potential intermediate phenotype for anxiety, an important step toward identification of causal pathways for vulnerability to affective disorders.
Identifiants
pubmed: 30711709
pii: S0925-4927(18)30186-0
doi: 10.1016/j.pscychresns.2019.01.010
pmc: PMC6699775
mid: NIHMS1520511
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
SLC6A4 protein, human
0
Serotonin Plasma Membrane Transport Proteins
0
BDNF protein, human
7171WSG8A2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-8Subventions
Organisme : NIMH NIH HHS
ID : F31 MH088066
Pays : United States
Organisme : NIMH NIH HHS
ID : R03 MH086709
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090257
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier B.V.
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