The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network".
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.
In recent years, accumulating data from various labs have demonstrated an A/T single-nucleotide polymorphism (SNP) resulting in (Asn107Ile) switch in the human NPSR gene as the risk factor for various psychiatric disorders such as panic disorder, post traumatic syndrome, alcohol use disorders and enhanced anxiety sensitivity, although, this is in stark contrast to the findings made in animal models which have consistently projected the anxiolytic nature of this peptide system.
Neuropeptide S is involved in anxiety and arousal modulation, and the functional polymorphism Asn107Ile (rs324981, A > T) of the neuropeptide S receptor gene (NPSR1) is associated with panic disorder and anxiety/fear-related traits.
The T allele of rs324981, which goes along with enhanced receptor function, was associated with panic disorder, increased anxiety sensitivity in healthy subjects, attenuated prefrontal brain activation and elevated amygdala responses to fear-relevant stimuli.
A functional variant within this gene leads to an amino-acid exchange (rs324981, Asn107Ile) resulting in a gain-of-function in the Ile107 variant which was recently associated with panic disorder in two independent studies.
The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach.