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

Cereb Cortex. 2017 Jan 1;27(1):554-566. doi: 10.1093/cercor/bhv259.

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.

Keywords: DCM; NPS; NPSR1; anxiety; dynamic causal modeling.

MeSH terms

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

Substances

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