Neuropeptide S Receptor Gene Variation Differentially Modulates Fronto-Limbic Effective Connectivity in Childhood and Adolescence.
The neuropeptide S (NPS) system contributes to the pathogenesis of anxiety. The more active T allele of the functional rs324981 variant in the neuropeptide S receptor gene (NPSR1) is associated with panic disorder (PD) and distorted cortico-limbic activity during emotion processing in healthy adults and PD patients. This study investigated the influence of NPSR1 genotype on fronto-limbic effective connectivity within the developing brain. Sixty healthy subjects (8-21 years) were examined using an emotional go-nogo task and fMRI. Fronto-limbic connectivity was determined using Dynamic Causal Modeling. In A allele carriers, connectivity between the right middle frontal gyrus (MFG) and the right amygdala was higher in older (≥14 years) than that in younger (<14 years) probands, whereas TT homozygotes ≥14 years showed a reduction of fronto-limbic connectivity between the MFG and both the amygdala and the insula. Fronto-limbic connectivity varied between NPSR1 genotypes in the developing brain suggesting a risk-increasing effect of the NPSR1T allele for anxiety-related traits via impaired top-down control of limbic structures emerging during adolescence. Provided robust replication in longitudinal studies, these findings may constitute valuable biomarkers for early targeted prevention of anxiety disorders.
Department of Psychiatry, Psychosomatics and Psychotherapy and.
Katharina
K
Domschke
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
Atae
A
Akhrif
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
Marcel
M
Romanos
Department of Diagnostical and Interventional Neuroradiology.|Department of Neurology and.
Christina
C
Bajer
Department of Diagnostical and Interventional Neuroradiology.|Department of Neurology and.
Margrit
M
Mainusch
Institute of Human Genetics, Technical University Munich, Munich, Germany.|Institute of Human Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Juliane
J
Winkelmann
Department of Diagnostical and Interventional Neuroradiology.
Claus
C
Zimmer
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
Susanne
S
Neufang
D000293:Adolescent; D001931:Brain Mapping; D002648:Child; D004644:Emotions / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000502:physiology*; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D007266:Inhibition, Psychological; D008032:Limbic System / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000254:growth & development / Q000502:physiology; D009483:Neuropsychological Tests; D010865:Pilot Projects; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D055815:Young Adult
C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled
DCM; NPS; NPSR1; anxiety; dynamic causal modeling