Gender-specific association of a functional coding polymorphism in the Neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder

A neuropeptide S receptor variant associated with overinterpretation of fear reactions: a potential neurogenetic basis for catastrophizing

“…2 First data indicate a link between this molecular alteration and human fear behavior in that the NPSR1 A allele has been shown to be under-represented in a sample of Japanese PD patients. 12 These results have recently been confirmed and extended in two large German samples (Domschke et al, in revision at Molecular Psychiatry).…”

“…Results from an exploratory whole-brain level analysis are reported in Supplementary Table S4 Because the T allele has been linked with PD, 12 our results are of theoretical interest for the understanding of PD etiology. They allow for hypothesizing that T allele carriers are at increased risk to develop PD because of an innate tendency to mis-interpret their affective responses to arousing or aversive stimuli in a catastrophizing manner.…”

Neuropeptide S receptor gene — converging evidence for a role in panic disorder

“…This finding strengthens recent evidence arising from animal models for a pivotal role of NPS in the expression of anxiety [3][4][5][6][7][9][10][11]49 and for a risk locus on chromosome 7p14 containing the NPSR gene in panic disorder. [22][23][24]27 Interestingly, in both samples comprising a total of 766 patients association of NPSR gene variation with panic disorder strongly originated from or was even restricted to the female subgroup of patients (n = 514). This finding is in line with previous molecular genetic reports of female-specific association findings in panic disorder possibly through hormonal interactions or female-specific transcriptional patterns.…”

“…The study was approved of by the ethics committee of Wü rzburg and written informed consent was obtained from all participating subjects. 27 explicitly reporting an underrepresentation of the homozygous AA genotype in patients with panic disorder. Both association studies have also been analyzed jointly using the same procedure; furthermore, meta-analytic treatment of the studies was performed: odds ratios (ORs) were calculated as a measure for effect size; thereafter, the Q-statistic 36,37 was applied to assess heterogeneity.…”

“…25,26 Homozygosity for the less active A allele (Asn 107 ) was found to be underrepresented in the male (n = 51) subgroup of 140 Japanese panic disorder patients, suggesting the higher active T (Ile 107 ) allele to constitute a risk factor for panic disorder. 27 In this study, a multilevel approach was applied to further elucidate the role of NPS in the pathogenesis of human anxiety. In detail, it was investigated whether the functional NPSR A/T (Asn 107 Ile) variant (rs324981) was associated (1) with the categorical phenotype of panic disorder with and without agoraphobia in two independent, large and wellcontrolled case-control studies; (2) with participants' scores on dimensional anxiety traits such as anxiety sensitivity; (3) with autonomic arousal level as reflected by heart rate and symptom ratings during a behavioral avoidance test (BAT) and (4) with brain activation correlates of anxiety-related emotional processing in patients with panic disorder with and without agoraphobia.…”