Neuropeptide S Receptor Gene Variation Differentially Modulates Fronto-Limbic Effective Connectivity in Childhood and Adolescence.

Abstract

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.

• Authors: Katharina Domschke, Atae Akhrif, Marcel Romanos, Christina Bajer, Margrit Mainusch, Juliane Winkelmann, Claus Zimmer, Susanne Neufang
• Journal: Cerebral cortex (New York, N.Y. : 1991) (Cereb Cortex) Vol. 27 Issue 1 Pg. 554-566 (01 01 2017) ISSN: 1460-2199 [Electronic] United States
• PMID: 26503268 (Publication Type: Journal Article)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• NPSR1 protein, human
• Receptors, G-Protein-Coupled

Topics

• Adolescent
• Brain Mapping
• Child
• Emotions (physiology)
• Female
• Frontal Lobe (diagnostic imaging, growth & development, physiology)
• Genotyping Techniques
• Heterozygote
• Humans
• Inhibition, Psychological
• Limbic System (diagnostic imaging, growth & development, physiology)
• Male
• Motor Activity (physiology)
• Neural Pathways (diagnostic imaging, growth & development, physiology)
• Neuropsychological Tests
• Pilot Projects
• Receptors, G-Protein-Coupled (genetics)
• Young Adult