Modulation of prefrontal functioning in attention systems by NPSR1 gene variation

Evidence has accumulated for a dysfunction of arousal and executive attention in anxiety. The neuropeptide S (NPS) system has been shown to play a pivotal role in the mediation of arousal and to be associated with anxiety/panic disorder. The present study aims at investigating the impact of functional neuropeptide S receptor (NPSR1) gene variation on neural attention patterns applying an imaging genetics approach. In an event-related functional magnetic resonance imaging (fMRI) setting, 47 healthy subjects (f=23) evenly pre-stratified for NPSR1 rs324981 A/T genotype were investigated for brain activation patterns while performing the Attention Network Task (ANT), simultaneously probing alerting and executive control functions. Anxiety sensitivity was ascertained by the Anxiety Sensitivity Index (ASI). In the alerting condition, NPSR1 TT homozygotes showed higher activations in the right prefrontal cortex and the locus coeruleus region as compared to A allele carriers. In the executive control condition, TT homozygotes displayed increased activations in fronto-parietal regions. Genotype-driven activation differences in the prefrontal cortex correlated with anxiety sensitivity, in both the alerting and the executive control system. The present results for the first time suggest NPSR1 gene variation to be associated with alterations of prefrontal functioning in the attentional functions alerting and executive control partly modulated by anxiety sensitivity. These findings may aid in unraveling the neurobiological underpinnings of distorted arousal and attention in anxiety and thereby possibly in the biomarker-guided development of preventive/therapeutic strategies targeting attention processes in anxiety disorders.