Modulation of prefrontal functioning in attention systems by NPSR1 gene variation

The genetics of anxiety‐related negative valence system traits

“…The norepinephrine‐activated alerting network is of particular relevance to NVS as it relates to hypervigilance and attentiveness/attentional biases toward threat [Geiger et al, ]. Genes demonstrating an association with the activation or function of the alerting network include ADRA2A [Green et al, ], NET [Green et al, ], NPSR1 (rs324981) [Neufang et al, ], the NMDA receptor subunit GRIN2B (rs1806201) [Schulz et al, ], CACNA1C (rs1006737) [Thimm et al, ] and, at a trend level only, the dopamine transmitter DAT1 (rs6350) [Konrad et al, ]. Other tested variants having no significant associations with the alerting network included TPH2 (rs4570625), ZNF804A (rs1344706), DTNBP1 (rs1018381), and COMT (rs4689) [Reuter et al, ; Thimm et al, ; Balog et al, ].…”

A functional variant of the neuropeptide S receptor‐1 gene modulates clinical outcomes and healthcare utilization in patients with systolic heart failure: results from the Interdisciplinary Network Heart Failure (INH) Study

“…T‐allele carriers exhibited activation of the dorsal anterior cingulate cortex during fear learning, indicating a cognitive overinterpretation of fear reactions . More recently, increased activation of the right prefrontal cortex was shown in TT genotype carriers during an Attentional Network Task, suggesting a role for NPSR1 both in integration of the perception of bodily symptoms (bottom‐up alerting) and in the subsequent cognitive response (executive neural control) . Correspondingly, significant interactions between genotype and environment have been observed, implicating an increased anxiety sensitivity in healthy persons with the homozygous TT genotype …”

“…To investigate whether the NPSR1 rs324981 A/T [Asn(107)Ile] polymorphism modulates outcomes in this severe somatic disease, we studied the characteristics and clinical course of patients discharged from hospital after acute cardiac decompensation according to NPSR1 genotype using data and biomaterials from the Interdisciplinary Network Heart Failure (INH) programme . In consideration of functionality, and previous studies on anxiety‐related phenotypes that suggested a recessive effect of the T‐allele, we primarily tested the hypothesis that clinical outcomes and healthcare utilization might differ between patients with the AT or AA genotype and homozygous carriers of the gain‐of‐function T‐allele (TT genotype) as a possible consequence of the genetically determined exaggerated perception of somatic symptoms and over‐reaching anxiety.…”

Functional neuroanatomy in panic disorder: Status quo of the research

“…The authors considered this activation to be part of an adaptive mechanism to compensate for presumably increased subcortical activity driven by an overactive NPS system. Neufang et al[123] investigated the impact of NPSR1 gene variations in 47 healthy subjects on cerebral activation patterns during a task probing alerting functions (Attention Network Task) using fMRI. In the alerting condition, homozygote TT allele carriers showed higher activation in the right PFC and the LC as compared to the AA/AT group.…”

“…Healthy subjects carrying the risk allele exhibit increased amygdala and PFC responses to anxiety related emotional stimuli[121]. During a probe of alerting function, higher activations in the right PFC and the LC have been observed in healthy risk allele carriers[123]. Results of a very recent study suggest that the NPSR1 T allele might be responsible for impaired top-down control of limbic structures during adolescence, therefore increasing the risk for possible anxiety-related traits[124].…”