Association of Neuropeptide S Receptor 1 and Glutamate Decarboxylase 1 Gene Polymorphisms With Posttraumatic Stress Disorder

Abstract

Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by highly traumatic experiences. The aim of this study was to investigate the influence of single nucleotide polymorphisms (SNPs) in the neuropeptide S receptor 1 (NPSR1) and the glutamate decarboxylase 1(GAD1) gene on PTSD and its psychopathological aspects among individuals affected by the Balkan wars during the 90s.Subjects and methods: This study was conducted as part of the South Eastern Europe (SEE) study on molecular mechanisms of PTSD. It comprised 719 participants (539 males), including those with current PTSD, remitted PTSD and healthy volunteers. Psychometric evaluation was performed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) andthe Brief Symptom Inventory (BSI). We examined NPSR1 single nucleotide polymorphism (SNP) rs324981 and GAD1 variant rs3749034 genotypes. Case-control analyses were carried out using logistical regression to determine genotype differences between all patients that had either current or remitted PTSD and control individuals. To analyse the influence of the analysed SNPs on PTSD severity, we performed linear regression analyses with CAPS and BSI within each of the two patient groups separately. All of the calculations were performed for additive allelic, recessive, dominant and genotypic models.Results: We observed a nominally significant association for the major allele (G) of GAD1 rs3749034 with an increased risk to develop PTSD in a case control analysis in the recessive model (P=0.0315, odds ratio=0.47, SE=0.35). In contrast, a nominally significant association of the minor allele (A) with higher CAPS scores was identified within the patient group with lifetime PTSD in the dominant model (P=0. 0372, =6.29, SE=2.99). None of these results did withstand correction for multiple tests. No nominal significant results of GAD1 rs3749034 were found with regard to the intensity of psychological BSI symptoms. Case-control analyses of NPSR1 rs324981 revealed a nominally significant higher risk for homozygous T allele carriers to develop PTSD (P=0.0452) in the recessive model. On the other hand, the T allele showed a nominally significant association with higher BSI scores in patients suffering from lifetime PTSD in the recessive model (P=0.0434). Again, these results were not significant anymore after correction for multiple tests. No associations of NPSR1 rs324981 and CAPS score was identified. Conclusion:The findings of this study provide some evidence that the NPSR1 and GAD1 polymorphisms might play a role in the development of war-related PTSD and its related psychological expressions. Further research is needed to elucidate the interactions of specific gene variants and environmental factors in the development of PTSD.

Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders

“…Similar to observations in PD, a trend for an underrepresentation of the AA genotype was observed in adult Asian patients with GAD compared to healthy controls [ 77 ]. In a recent study, an increased risk in developing PTSD following the Balkan war was revealed in carriers of the TT genotype [ 78 ]. Since the study of He and colleagues observed that the chronic administration of venlafaxine, a serotonin and norepinephrine reuptake inhibitor antidepressant, produced a greater reduction in anxiety symptom severity in GAD patients carriers of the AA or TT genotype compared to those with the AT genotype, further investigation of the impact of the SNP rs324981 on anxiety disease risk and response to pharmacological treatment is definitively required.…”

Roles of Neuropeptide S in Anesthesia, Analgesia, and Sleep

“…Thus, surgical stress alone could result in sleep disturbances. As NPS has an anti-stress action [ 74 ], the NPS–NPSR system is a research target to improve surgical stress-induced sleep disturbances. Opioids are widely used as common analgesics for surgical wounds because opioids have a prominent analgesic effect.…”